Cancer Drug Interactions from Radboud UMC and University of Liverpool

No Interaction Expected

Erlotinib

Acarbose

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. After ingestion of acarbose, the majority of active unchanged drug remains in the lumen of the gastrointestinal tract to exert its pharmacological activity and is metabolised by intestinal enzymes and by the microbial flora. Erlotinib does not interact with this metabolic pathway.

Description:

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Potential Interaction

Erlotinib

Acenocoumarol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Acenocoumarol is mainly metabolised by CYP2C9 and to a lesser extent by CYP1A2 and CYP2C19. Erlotinib does not inhibit or induce CYPs 2C9, 1A2 or 2C19. However, interaction of erlotinib with coumarin-derived anticoagulants leads to an increased International Normalized Ratio (INR) and increased bleeding adverse events. Monitor closely for INR or prothrombin time changes.

Description:

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No Interaction Expected

Erlotinib

Acetylsalicylic acid (Aspirin)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Aspirin is rapidly deacetylated to form salicylic acid and then further metabolised by glucuronidation (by several UGTs, major UGT1A6). Erlotinib does not inhibit or induce UGT1A6.

Description:

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No Interaction Expected

Erlotinib

Agomelatine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Agomelatine is metabolised predominantly via CYP1A2 (90%), with a small proportion metabolised by CYP2C9 and CYP2C19 (10%). Erlotinib does not inhibit or induce CYPs 1A2, 2C9 or 2C19.

Description:

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No Interaction Expected

Erlotinib

Alendronic acid

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Alendronic acid is not metabolised and is cleared from the plasma by uptake into bone and elimination via renal excretion. Although no pharmacokinetic interaction is expected, alendronic acid should be separated from food or other medicinal products and patients must wait at least 30 minutes after taking alendronic acid before taking any other oral medicinal product.

Description:

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No Interaction Expected

Erlotinib

Alfentanil

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Alfentanil undergoes extensive CYP3A4 metabolism and concentrations may increase due to moderate inhibition by erlotinib. However, after coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. Moreover, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on alfentanil exposure is expected.

Description:

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No Interaction Expected

Erlotinib

Alfuzosin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Alfuzosin is metabolised by CYP3A. Concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on alfuzosin exposure is expected.

Description:

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No Interaction Expected

Erlotinib

Aliskiren

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Aliskiren is minimally metabolised and is mainly excreted unchanged in faeces. Aliskiren is also a substrate of P-gp. Erlotinib is unlikely to interfere with this elimination pathway and does not inhibit or induce P-gp.

Description:

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No Interaction Expected

Erlotinib

Allopurinol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Allopurinol is converted to oxipurinol by xanthine oxidase and aldehyde oxidase. Allopurinol is also an inhibitor of xanthine oxidase. Erlotinib does not interact with this metabolic pathway.

Description:

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No Interaction Expected

Erlotinib

Alosetron

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. In vitro data indicate that alosetron is metabolised by CYPs 2C9, 3A4 and 1A2. Concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on alosetron exposure is expected.

Description:

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No Interaction Expected

Erlotinib

Alprazolam

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Alprazolam is mainly metabolised by CYP3A4 and concentrations may increase due to moderate inhibition by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on alprazolam exposure is expected.

Description:

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Potential Weak Interaction

Erlotinib

Aluminium hydroxide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Aluminium hydroxide is not metabolised. However, the bioavailability of erlotinib is pH-dependent and, thus, an increase in gastric pH by aluminium hydroxide reduces its bioavailability. Results on whether this decrease in exposure will lead to a decreased efficacy of erlotinib are conflicting. If coadministration is clinically necessary, erlotinib should be administered at the moment at which antacid action is unlikely, and that is just before a new dose of aluminium hydroxide.

Description:

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No Interaction Expected

Erlotinib

Ambrisentan

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ambrisentan is metabolized by glucuronidation via UGT1A3, UGT1A9 and UGT2B7 and to a lesser extent by CYP3A4 and CYP2C19. Ambrisentan is also substrate of P-gp. Concentrations of ambrisentan may alter due to moderate inhibition of CYP3A4 by erlotinib. However, since CYP3A4 represents a minor pathway no clinically relevant effect on ambrisentan exposure is expected. Erlotinib does not inhibit or induce UGTs 1A3, 1A9, 2B7, CYP2C19 or P-gp.

Description:

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No Interaction Expected

Erlotinib

Amikacin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amikacin is eliminated by glomerular filtration. Erlotinib is unlikely to interfere with this elimination pathway.

Description:

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No Interaction Expected

Erlotinib

Amiloride

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amiloride is eliminated unchanged in the kidney. In vitro data indicate that amiloride is a substrate of OCT2. Erlotinib is unlikely to interfere with this elimination pathway and does not inhibit or induce OCT2.

Description:

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Potential Interaction

Erlotinib

Amiodarone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Amiodarone is metabolised by CYP3A4 and CYP2C8. Concentrations may increase due to moderate inhibition of CYP3A4 and CYP2C8 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, oral midazolam exposure decreased by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on amiodarone exposure is expected. Moreover, the major metabolite of amiodarone, desethylamiodarone, is an inhibitor of CYP3A4 (weak), CYP2C9 (moderate), CYP2D6 (moderate), CYP2C19 (weak), CYP1A1 (strong), CYP2B6 (moderate) and P-gp (strong). Erlotinib is metabolised by CYP3A4 (~70%) and concentrations may increase due to inhibition by amiodarone. After coadministration with ketoconazole, a strong CYP3A4 inhibitor, erlotinib exposure increased by 86%. A similar effect may occur after coadministration with amiodarone. Erlotinib is dosed at/near the maximum tolerated dose (MTD) and thus, any increase in erlotinib exposure may lead to toxicity. A case of severe neurotoxicity after concomitant treatment of amiodarone (200 mg twice daily) and erlotinib (150 mg once daily) has been described in a 64-year-old male. P-gp inhibition by amiodarone was thought to cause this neurotoxicity as P-gp is involved in limiting the blood-brain barrier penetration of erlotinib. Coadministration should be approached with caution. If coadministration is unavoidable, reduce erlotinib dose by 50mg decrements. Monitor closely for erlotinib toxicity and, if available, erlotinib plasma concentrations. Note: due to the long half-life of amiodarone, interactions can be observed for several months after discontinuation of amiodarone.

Description:

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No Interaction Expected

Erlotinib

Amisulpride

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amisulpride is weakly metabolised and is primarily eliminated renally (possibly via OCT). Erlotinib is unlikely to interfere with this elimination pathway and does not inhibit or induce OCTs.

Description:

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No Interaction Expected

Erlotinib

Amitriptyline

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amitriptyline is metabolised predominantly by CYP2D6 and CYP2C19, with a small proportion metabolised by CYPs 3A4, 1A2 and 2C9. Concentrations of amitriptyline may alter due to moderate inhibition of CYP3A4 by erlotinib. However, since CYP3A4 represents a minor pathway no clinically relevant effect on amitriptyline exposure is expected. Erlotinib does not inhibit or induce CYPs 2D6, 2C19, 1A2 or 2C9.

Description:

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No Interaction Expected

Erlotinib

Amlodipine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amlodipine is metabolised by CYP3A4 and concentrations may increase due to moderate inhibition by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on amlodipine exposure is expected.

Description:

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No Interaction Expected

Erlotinib

Amoxicillin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amoxicillin is mainly excreted in the urine by glomerular filtration and tubular secretion. In vitro data indicate that amoxicillin is a substrate of OAT3. Erlotinib is unlikely to interfere with this elimination pathway and does not inhibit or induce OAT3.

Description:

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No Interaction Expected

Erlotinib

Amphotericin B

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amphotericin B is not appreciably metabolised and is eliminated to a large extent in the bile. Erlotinib does not interfere with this metabolic or elimination pathway.

Description:

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No Interaction Expected

Erlotinib

Ampicillin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Renal clearance of ampicillin occurs partly by glomerular filtration and partly by tubular secretion. About 20-40% of an oral dose may be excreted unchanged in the urine in 6 hours. After parenteral use about 60-80% is excreted in the urine within 6 hours. Erlotinib is unlikely to interfere with this elimination pathway.

Description:

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No Interaction Expected

Erlotinib

Anidulafungin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Anidulafungin is not metabolised hepatically but undergoes chemical degradation at physiological temperatures. Erlotinib does not interact with this metabolic pathway.

Description:

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Potential Weak Interaction

Erlotinib

Antacids

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Antacids are not metabolised by CYPs. However, the bioavailability of erlotinib is pH-dependent and, thus, an increase in gastric pH by antacids reduces its bioavailability. Results whether this decrease in exposure will lead to a decreased efficacy of erlotinib are conflicting. If coadministration is clinically necessary, erlotinib should be administered at the moment at which antacid action is unlikely, and that is just before a new dose of the antacid.

Description:

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No Interaction Expected

Erlotinib

Apixaban

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Apixaban is a substrate of P-gp and BCRP, and is metabolised by CYP3A4 and to a lesser extent by CYPs 1A2, 2C8, 2C9 and 2C19. Concentrations of apixaban may alter due to moderate inhibition of CYP3A4 and CYP2C8 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on apixaban exposure is expected

Description:

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Potential Interaction

Erlotinib

Aprepitant

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Aprepitant is mainly metabolized by CYP3A4 and to a lesser extent by CYP1A2 and CYP2C19. Concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on aprepitant exposure is expected. During treatment aprepitant is a moderate inhibitor of CYP3A4. Moreover, after treatment aprepitant is a weak inducer of CYP3A4, CYP2C9 and UGT. Erlotinib is metabolised by CYP3A4 (~70%) and concentrations may increase due to inhibition by aprepitant during treatment. After coadministration with ketoconazole, a strong CYP3A4 inhibitor, erlotinib exposure increased by 86%. A similar effect may occur after coadministration with aprepitant. Erlotinib is dosed at/near the maximum tolerated dose (MTD) and thus, any increase in erlotinib exposure may lead to toxicity. Coadministration should be approached with caution. If coadministration is unavoidable, reduce erlotinib dose by 50mg decrements. Monitor closely for erlotinib toxicity and, if available, erlotinib plasma concentrations.

Description:

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No Interaction Expected

Erlotinib

Aripiprazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Aripiprazole is metabolised by CYP3A4 and CYP2D6. Concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on aripiprazole exposure is expected.

Description:

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No Interaction Expected

Erlotinib

Asenapine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Asenapine is metabolised by glucuronidation (UGT1A4) and oxidative metabolism (CYPs 1A2 (major), 3A4 (minor) and 2D6 (minor)). Concentrations of asenapine may alter due to moderate inhibition of CYP3A4 by erlotinib. However, since CYP3A4 represents a minor pathway no clinically relevant effect on asenapine exposure is expected. Erlotinib does not inhibit or induce UGT1A4, CYP1A2 or CYP2D6.

Description:

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No Interaction Expected

Erlotinib

Astemizole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Astemizole is metabolised by CYPs 2D6, 2J2 and 3A4. Concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on astemizole exposure is expected.

Description:

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No Interaction Expected

Erlotinib

Atenolol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Atenolol is mainly eliminated unchanged in the kidney, predominantly by glomerular filtration. Erlotinib is unlikely to interfere with this elimination pathway.

Description:

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No Interaction Expected

Erlotinib

Atorvastatin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Atorvastatin is metabolised by CYP3A4 and is a substrate of P-gp and OATP1B1. Concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on atorvastatin exposure is expected.

Description:

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No Interaction Expected

Erlotinib

Azathioprine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Azathioprine is converted to 6-mercaptopurine which is metabolised analogously to natural purines by xanthine oxidase. Erlotinib does not interact with this metabolic pathway.

Description:

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No Interaction Expected

Erlotinib

Azithromycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Azithromycin is mainly eliminated via biliary excretion; animal data suggest this may occur via P-gp and MRP2. Azithromycin is also an inhibitor of P-gp. However, the clinical relevance of P-gp inhibition by azithromycin is unknown. Erlotinib is unlikely to interfere with this elimination or metabolic pathway.

Description:

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No Interaction Expected

Erlotinib

Beclometasone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Beclometasone is a pro-drug which is not metabolised by CYP450, but is hydrolysed via esterase enzymes to the highly active metabolite beclometasone-17-monopropionate. Erlotinib does not interact with this metabolic pathway.

Description:

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No Interaction Expected

Erlotinib

Bedaquiline

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bedaquiline is metabolised by CYP3A4 and concentrations may increase due to moderate inhibition by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on bedaquiline exposure is expected.

Description:

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No Interaction Expected

Erlotinib

Bendroflumethiazide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bendroflumethiazide is mainly eliminated by hepatic metabolism (70%) and excreted unchanged in the urine (30%) via OAT1 and OAT3. In vitro data indicate that bendroflumethiazide inhibits these renal transporters but a clinically significant interaction is unlikely in the range of observed clinical concentrations. Erlotinib is unlikely to interfere with this metabolic pathway and does not inhibit or induce OATs.

Description:

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No Interaction Expected

Erlotinib

Bepridil

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bepridil is metabolised by CYP2D6 (major) and CYP3A4. Concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on bepridil exposure is expected.

Description:

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No Interaction Expected

Erlotinib

Betamethasone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Betamethasone is metabolised by CYP3A4 and concentrations may increase due to moderate inhibition by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on betamethasone exposure is expected.

Description:

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No Interaction Expected

Erlotinib

Bezafibrate

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Half of a bezafibrate dose is eliminated unchanged in the urine. In vitro data suggest that bezafibrate inhibits the renal transporter OAT1. Erlotinib is unlikely to interfere with this elimination pathway.

Description:

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No Interaction Expected

Erlotinib

Bisacodyl

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bisacodyl is converted to an active metabolite by intestinal and bacterial enzymes. Absorption from the gastrointestinal tract is minimal and the small amount absorbed is excreted in the urine as the glucuronide. Erlotinib is unlikely to interfere with this metabolic or elimination pathway.

Description:

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No Interaction Expected

Erlotinib

Bisoprolol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bisoprolol is partly metabolised by CYP3A4 and CYP2D6, and partly eliminated unchanged in the urine. Concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on bisoprolol exposure is expected.

Description:

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Do Not Coadminister

Erlotinib

Bosentan

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be avoided. Bosentan is a substrate and weak inducer of CYP3A4 and CYP2C9. Erlotinib is metabolised by CYP3A4 (~70%) and concentrations may decrease due to induction by bosentan. After coadministration with rifampicin, a strong CYP3A4 inducer, erlotinib exposure decreased by 69%. A similar effect may occur after coadministration with bosentan, although the magnitude and relevancy of the effect are unknown. Avoid concomitant use. If coadministration is unavoidable, increase erlotinib dosage by 50 mg at 2-week intervals to a maximum of 450 mg as tolerated. Monitor erlotinib plasma concentrations, if available.

Description:

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No Interaction Expected

Erlotinib

Bromazepam

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bromazepam undergoes oxidative biotransformation. Interaction studies indicate that CYP3A4 plays a minor role in bromazepam metabolism, but other cytochromes such as CYP2D6 or CYP1A2 may also play a role. Concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on bromazepam exposure is expected.

Description:

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No Interaction Expected

Erlotinib

Budesonide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Budesonide is metabolised by CYP3A4 and concentrations may increase due to moderate inhibition by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on budesonide exposure is expected.

Description:

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No Interaction Expected

Erlotinib

Buprenorphine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Buprenorphine undergoes both N-dealkylation to form norbuprenorphine (via CYP3A4) and glucuronidation (via UGT2B7 and UGT1A1). Concentrations may increase due to inhibition of UGT1A1 by erlotinib, but this effect is only established in vitro. Moreover, concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no relevant effects on buprenorphine exposure are expected.

Description:

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No Interaction Expected

Erlotinib

Bupropion

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bupropion is primarily metabolised by CYP2B6 and is a strong inhibitor of CYP2D6. Erlotinib does not interact with this metabolic pathway.

Description:

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No Interaction Expected

Erlotinib

Buspirone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Buspirone is metabolised by CYP3A4 and concentrations may increase due to moderate inhibition by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on buspirone exposure is expected.

Description:

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No Interaction Expected

Erlotinib

Calcium

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Calcium is eliminated through faeces, urine and sweat. Erlotinib is unlikely to interfere with this elimination pathway.

Description:

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No Interaction Expected

Erlotinib

Candesartan

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Candesartan is mainly eliminated unchanged via urine and bile. Erlotinib is unlikely to interfere with this elimination pathway.

Description:

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No Interaction Expected

Erlotinib

Capreomycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Capreomycin is predominantly excreted via the kidneys as unchanged drug. Erlotinib is unlikely to interfere with this elimination pathway.

Description:

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No Interaction Expected

Erlotinib

Captopril

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Captopril is largely excreted in the urine by OAT1. Erlotinib does not inhibit or induce OAT1.

Description:

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Do Not Coadminister

Erlotinib

Carbamazepine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is contraindicated. Carbamazepine is primarily metabolized by CYP3A4 and to a lesser extent by CYP2C8 and concentrations may increase due to moderate inhibition by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on carbamazepine exposure is expected. Carbamazepine is also an inducer of CYP2C8 (strong), CYP2C9 (strong), CYP3A4 (strong), CYP1A2 (weak), CYP2B6, UGT1A1 and P-gp (moderate). Erlotinib is metabolised by CYP3A4 (~70%) and concentrations may decrease due to induction by carbamazepine. After coadministration with rifampicin, a strong CYP3A4 inducer, erlotinib exposure decreased by 69%. A similar effect may occur after coadministration with carbamazepine, although the magnitude and relevancy of the effect are unknown. Avoid concomitant use. If coadministration is unavoidable, increase erlotinib dosage by 50 mg at 2-week intervals to a maximum of 450 mg as tolerated. Monitor erlotinib plasma concentrations, if available.

Description:

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No Interaction Expected

Erlotinib

Carvedilol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Carvedilol undergoes glucuronidation via UGTs 1A1, 2B4 and 2B7, and additionally metabolism via CYP2D6 and to a lesser extent CYP2C9 and CYP1A2. Concentrations may increase due to inhibition of UGT1A1 by erlotinib, but this effect is only established in vitro. Therefore, no clinically relevant effect on carvedilol exposure is expected. Carvedilol is also an inhibitor of P-gp. However, the clinical relevance of P-gp inhibition by carvedilol is unknown.

Description:

See summary

No Interaction Expected

Erlotinib

Caspofungin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Caspofungin undergoes spontaneous chemical degradation and metabolism via a non CYP-mediated pathway. Erlotinib does not interact with this metabolic pathway.

Description:

See summary

No Interaction Expected

Erlotinib

Cefalexin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cefalexin is predominantly eliminated unchanged renally by glomerular filtration and tubular secretion via OAT1 and MATE1. Erlotinib is unlikely to interfere with this elimination pathway and does not inhibit or induce OAT1 or MATE1.

Description:

See summary

No Interaction Expected

Erlotinib

Cefazolin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cefazolin is predominantly excreted unchanged in the urine, mainly by glomerular filtration with some renal tubular secretion via OAT3. Erlotinib is unlikely to interfere with this elimination pathway and does not inhibit or induce OAT3.

Description:

See summary

No Interaction Expected

Erlotinib

Cefixime

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cefixime is renally excreted predominantly by glomerular filtration. Erlotinib is unlikely to interfere with this elimination pathway.

Description:

See summary

No Interaction Expected

Erlotinib

Cefotaxime

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cefotaxime is partially metabolised by non-specific esterases. Most of a dose of cefotaxime is excreted in the urine - about 60% as unchanged drug and a further 24% as desacetyl-cefotaxime, an active metabolite. In vitro studies indicate that OAT3 participates in the renal elimination of cefotaxime. Erlotinib is unlikely to interfere with this metabolic or elimination pathway and does not inhibit or induce OAT3.

Description:

See summary

No Interaction Expected

Erlotinib

Ceftazidime

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ceftazidime is excreted predominantly by renal glomerular filtration. Erlotinib is unlikely to interfere with this elimination pathway.

Description:

See summary

No Interaction Expected

Erlotinib

Ceftriaxone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ceftriaxone is eliminated mainly as unchanged drug, approximately 60% of the dose being excreted in the urine predominantly by glomerular filtration and the remainder via the biliary and intestinal tracts. Erlotinib is unlikely to interfere with this elimination pathway.

Description:

See summary

No Interaction Expected

Erlotinib

Celecoxib

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Celecoxib is primarily metabolised by CYP2C9. Erlotinib does not inhibit or induce CYP2C9.

Description:

See summary

No Interaction Expected

Erlotinib

Cetirizine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cetirizine is only metabolised to a limited extent and is eliminated unchanged in the urine through both glomerular filtration and tubular secretion. In vitro data indicate that cetirizine is also an inhibitor of OCT2. Erlotinib is unlikely to interfere with this metabolic or elimination pathway.

Description:

See summary

Potential Interaction

Erlotinib

Chloramphenicol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Chloramphenicol is predominantly glucuronidated. Chloramphenicol concentrations may increase due to inhibition of UGT1A1 by erlotinib, but this effect is only established in vitro. Therefore, no relevant effect on chloramphenicol exposure is expected. In vitro studies have shown that chloramphenicol can inhibit metabolism mediated by CYP3A4 (strong), CYP2C19 (strong) and CYP2D6 (weak). Erlotinib is metabolised by CYP3A4 (~70%) and concentrations may increase due to inhibition by chloramphenicol. After coadministration with ketoconazole, a strong CYP3A4 inhibitor, erlotinib exposure increased by 86%. A similar effect may occur after coadministration with chloramphenicol. Erlotinib is dosed at/near the maximum tolerated dose (MTD) and thus, any increase in erlotinib exposure may lead to toxicity. Coadministration should be approached with caution. If coadministration is unavoidable, reduce erlotinib dose by 50mg decrements. Monitor closely for erlotinib toxicity and, if available, erlotinib plasma concentrations. Ocular use: Although chloramphenicol is systemically absorbed when used topically in the eye, the absorbed concentrations are unlikely to cause a clinically significant interaction.

Description:

See summary

No Interaction Expected

Erlotinib

Chlordiazepoxide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Chlordiazepoxide is extensively metabolised by CYP3A4, but does not inhibit or induce cytochromes. Concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on chlordiazepoxide exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Chlorphenamine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Chlorphenamine is predominantly metabolised in the liver via CYP2D6. Erlotinib does not inhibit or induce CYP2D6.

Description:

See summary

No Interaction Expected

Erlotinib

Chlorpromazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Chlorpromazine is metabolised mainly by CYP2D6, but also by CYP1A2. Erlotinib does not inhibit or induce CYP2D6 or CYP1A2.

Description:

See summary

No Interaction Expected

Erlotinib

Chlortalidone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Chlortalidone is mainly excreted unchanged in the urine and faeces. OAT1/3 are the major transporters of loop and thiazide diuretics, which are not affected by erlotinib. Secretion of these diuretics into the urinary tract by transporters in the proximal tubular cells is necessary for the diuretic effect in later tubule segments. Erlotinib is unlikely to interfere with this elimination pathway and does not inhibit or induce OATs.

Description:

See summary

Potential Interaction

Erlotinib

Ciclosporin (Cyclosporine)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Ciclosporin is a substrate of CYP3A4 and P-gp. Concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on ciclosporin exposure is expected. Ciclosporin also inhibits CYP3A4 and OATP1B1. Erlotinib is metabolised by CYP3A4 (~70%) and concentrations may increase due to inhibition by ciclosporin. After coadministration with ketoconazole, a strong CYP3A4 inhibitor, erlotinib exposure increased by 86%. A similar effect may occur after coadministration with ciclosporin. Erlotinib is dosed at/near the maximum tolerated dose (MTD) and thus, any increase in erlotinib exposure may lead to toxicity. Coadministration should be approached with caution. If coadministration is unavoidable, reduce erlotinib dose by 50mg decrements. Monitor closely for erlotinib toxicity and, if available, erlotinib plasma concentrations.

Description:

See summary

No Interaction Expected

Erlotinib

Cilazapril

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cilazapril is mainly eliminated unchanged by the kidneys. Erlotinib is unlikely to interfere with this elimination pathway.

Description:

See summary

Potential Interaction

Erlotinib

Cimetidine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Cimetidine is metabolised by CYP450 enzymes. Concentrations may increase due to moderate inhibition of CYP3A4 and CYP2C8 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on cimetidine exposure is expected. In vitro data indicate that cimetidine inhibits OAT1 and OCT2. Erlotinib is not a substrate of OAT1 or OCT2. Cimetidine is also a weak inhibitor of CYPs 3A4, 1A2, 2D6 and 2C19. Erlotinib is metabolised by CYP3A4 (~70%) and concentrations may increase due to inhibition by cimetidine. After coadministration with ketoconazole, a strong CYP3A4 inhibitor, erlotinib exposure increased by 86%. A similar effect may occur after coadministration with cimetidine. Erlotinib is dosed at/near the maximum tolerated dose (MTD) and thus, any increase in erlotinib exposure may lead to toxicity. Coadministration should be approached with caution. If coadministration is unavoidable, reduce erlotinib dose by 50mg decrements. Monitor closely for erlotinib toxicity and, if available, erlotinib plasma concentrations.

Description:

See summary

Potential Interaction

Erlotinib

Ciprofloxacin

Quality of Evidence: Low

Summary:

Coadministration has been studied and should be approached with caution. Ciprofloxacin is primarily eliminated unchanged by the kidneys by glomerular filtration and tubular secretion via OAT3. It is also metabolised and partially cleared through the bile and intestine. Erlotinib is unlikely to interfere with this elimination pathway and does not inhibit or induce OAT3. Ciprofloxacin is also a weak to moderate inhibitor of CYP3A4 and a strong inhibitor of CYP1A2. Erlotinib is metabolised by CYP3A4 (~70%) and CYP1A2 (~30%) and concentrations will increase due to inhibition by ciprofloxacin. In healthy subjects (n=28), coadministration of erlotinib (100 mg single dose, day 1 and 15) with ciprofloxacin (750 mg twice daily, days 13-18), increased erlotinib exposure by 39% compared to erlotinib alone. Erlotinib is dosed at/near the maximum tolerated dose (MTD) and thus, any increase in erlotinib exposure may lead to toxicity. Coadministration should be approached with caution. If coadministration is unavoidable, reduce erlotinib dose by 50mg decrements. Monitor closely for erlotinib toxicity and, if available, erlotinib plasma concentrations.

Description:

See summary

No Interaction Expected

Erlotinib

Cisapride

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cisapride is metabolised by CYP3A4 and concentrations may increase due to moderate inhibition by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on cisapride exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Citalopram

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Citalopram is metabolised by CYPs 2C19 (38%), 2D6 (31%) and 3A4 (31%). Concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on citalopram exposure is expected.

Description:

See summary

Potential Interaction

Erlotinib

Clarithromycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Clarithromycin is metabolised by CYP3A4 and is also an inhibitor of CYP3A4 (strong) and P-gp. Clarithromycin concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on clarithromycin exposure is expected. Moreover, erlotinib is metabolised by CYP3A4 (~70%) and concentrations may increase due to inhibition by clarithromycin. After coadministration with ketoconazole, a strong CYP3A4 inhibitor, erlotinib exposure increased by 86%. A similar effect may occur after coadministration with clarithromycin. Erlotinib is dosed at/near the maximum tolerated dose (MTD) and thus, any increase in erlotinib exposure may lead to toxicity. Coadministration should be approached with caution. If coadministration is unavoidable, reduce erlotinib dose by 50mg decrements. Monitor closely for erlotinib toxicity and, if available, erlotinib plasma concentrations.

Description:

See summary

No Interaction Expected

Erlotinib

Clavulanic acid

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clavulanic acid is extensively metabolised (likely non-CYP mediated pathway) and excreted in the urine by glomerular filtration. Erlotinib is unlikely to interfere with this unspecified metabolic or elimination pathway.

Description:

See summary

No Interaction Expected

Erlotinib

Clemastine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clemastine is predominantly metabolised in the liver via CYP2D6. Erlotinib does not inhibit or induce CYP2D6.

Description:

See summary

Potential Interaction

Erlotinib

Clindamycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Clindamycin is metabolised by CYP3A4 and in vitro data suggest that it is a CYP3A4 inhibitor. Clindamycin concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on clindamycin exposure is expected. Moreover, erlotinib is metabolised by CYP3A4 (~70%) and concentrations may increase due to inhibition by clindamycin. After coadministration with ketoconazole, a strong CYP3A4 inhibitor, erlotinib exposure increased by 86%. A similar effect may occur after coadministration with clindamycin. Erlotinib is dosed at/near the maximum tolerated dose (MTD) and thus, any increase in erlotinib exposure may lead to toxicity. Coadministration should be approached with caution. If coadministration is unavoidable, reduce erlotinib dose by 50mg decrements. Monitor closely for erlotinib toxicity and, if available, erlotinib plasma concentrations.

Description:

See summary

No Interaction Expected

Erlotinib

Clobetasol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely with the topical use of clobetasol.

Description:

See summary

Potential Interaction

Erlotinib

Clofazimine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Clofazimine is largely excreted unchanged in the faeces. In vitro data suggest that clofazimine is a CYP3A4 inhibitor. Erlotinib is metabolised by CYP3A4 (~70%) and concentrations may increase due to inhibition by clofazimine. After coadministration with ketoconazole, a strong CYP3A4 inhibitor, erlotinib exposure increased by 86%. A similar effect may occur after coadministration with clofazimine. Erlotinib is dosed at/near the maximum tolerated dose (MTD) and thus, any increase in erlotinib exposure may lead to toxicity. Coadministration should be approached with caution. If coadministration is unavoidable, reduce erlotinib dose by 50mg decrements. Monitor closely for erlotinib toxicity and, if available, erlotinib plasma concentrations.

Description:

See summary

No Interaction Expected

Erlotinib

Clofibrate

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clofibrate is hydrolysed to an active metabolite, clofibric acid. Excretion of clofibric acid glucuronide is possibly performed via OAT1. Erlotinib is unlikely to interfere with this metabolic pathway and does not inhibit or induce OATs.

Description:

See summary

No Interaction Expected

Erlotinib

Clomipramine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clomipramine is metabolised by CYPs 3A4, 1A2 and 2C19 to desmethylclomipramine, an active metabolite which has a higher activity than the parent drug. Concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on clomipramine exposure is expected. In addition, clomipramine and desmethylclomipramine are metabolised by CYP2D6. Erlotinib does not inhibit or induce CYP2D6.

Description:

See summary

No Interaction Expected

Erlotinib

Clonidine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Approximately 70% of administered clonidine is excreted in the urine, mainly in form of the unchanged parent drug (40-60% of the dose). Clonidine is also a weak inhibitor of OCT2. Erlotinib is unlikely to interfere with this elimination pathway and does not inhibit or induce OCT2.

Description:

See summary

No Interaction Expected

Erlotinib

Clopidogrel

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clopidogrel is a prodrug and is converted to its active metabolite mainly through CYP2C19 with CYPs 3A4, 2B6 and 1A2 playing a minor role. Concentrations of clopidogrel may alter due to moderate inhibition of CYP3A4 by erlotinib. However, since CYP3A4 represents a minor pathway no clinically relevant effect on clopidogrel exposure is expected. Erlotinib does not inhibit or induce CYPs 2C19, 2B6 or 1A2. Clopidogrel is also an inhibitor of CYP2C8 (strong), CYP2B6 (weak) and in vitro of CYP2C9 at high concentrations. The clinical relevance of CYP2C9 inhibition is unknown. Erlotinib is not metabolised by CYPs 2C8, 2B6 or 2C9.

Description:

See summary

No Interaction Expected

Erlotinib

Clorazepate

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clorazepate is rapidly converted to nordiazepam which is then metabolised to oxazepam by CYP3A4. Oxazepam is mainly glucuronidated. Concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on clorazepate exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Cloxacillin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cloxacillin is metabolised to a limited extent, and the unchanged drug and metabolites are excreted in the urine by glomerular filtration and renal tubular secretion. Erlotinib is unlikely to interfere with this metabolic or elimination pathway.

Description:

See summary

No Interaction Expected

Erlotinib

Clozapine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clozapine is metabolised mainly by CYP1A2 and CYP3A4, and to a lesser extent by CYP2C19 and CYP2D6. Concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on clozapine exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Codeine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Codeine is converted via CYP2D6 to morphine, an active metabolite with analgesic and opioid properties. Erlotinib does not inhibit or induce CYP2D6. Morphine is further metabolized by conjugation with glucuronic acid to morphine-3-glucuronide (inactive) and morphine-6-glucuronide (active). Codeine is converted via CYP3A4 to norcodeine, an inactive metabolite. Concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on codeine exposure is expected. Additionally, the metabolite morphine is a substrate of P-gp. Erlotinib does not inhibit or induce P-gp.

Description:

See summary

No Interaction Expected

Erlotinib

Colchicine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Colchicine is metabolised by CYP3A4 and is a substrate of P-gp. Concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on colchicine exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Cycloserine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cycloserine is predominantly excreted renally via glomerular filtration. Erlotinib is unlikely to interfere with this elimination pathway.

Description:

See summary

No Interaction Expected

Erlotinib

Dabigatran

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dabigatran is transported via P-gp and is renally excreted. Erlotinib does not inhibit or induce P-gp and is unlikely to interfere with this elimination pathway.

Description:

See summary

No Interaction Expected

Erlotinib

Dalteparin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dalteparin is excreted largely unchanged via the kidneys. Erlotinib is unlikely to interfere with this elimination pathway.

Description:

See summary

No Interaction Expected

Erlotinib

Dapsone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metabolism of dapsone is mainly by N-acetylation with a component of N-hydroxylation, and is via multiple CYP450 enzymes. Dapsone concentrations may increase due to moderate CYP3A4 inhibition by erlotinib. However, since multiple CYP450 enzymes are involved, no clinically relevant effect on dapsone exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Desipramine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Desipramine is metabolised by CYP2D6. Erlotinib does not inhibit or induce CYP2D6.

Description:

See summary

No Interaction Expected

Erlotinib

Desogestrel

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Desogestrel is a prodrug which is activated to etonogestrel by CYP2C9 (and possibly CYP2C19); the metabolism of etonogestrel is mediated by CYP3A4. Concentrations of etonogestrel may alter due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on etonogestrel exposure is expected.

Description:

See summary

Potential Weak Interaction

Erlotinib

Dexamethasone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Dexamethasone has been described as a weak inducer of CYP3A4. Erlotinib is metabolized by CYP3A4 and plasma concentrations may decrease due to induction by dexamethasone. However, the clinical relevance of this interaction is not known. Moreover, the induction of CYP3A4 by dexamethasone has not been established yet. Monitor erlotinib plasma concentrations, if available. Furthermore, dexamethasone is a substrate of CYP3A4 and concentrations may increase due to moderate inhibition by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on dexamethasone exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Dextropropoxyphene

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dextropropoxyphene is mainly metabolised by CYP3A4 and concentrations may increase due to moderate inhibition by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on dextropropoxyphene exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Diamorphine (diacetylmorphine)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Diamorphine is rapidly metabolised by sequential deacetylation to morphine which is then mainly glucuronidated to morphine-3-glucuronide (UGT2B7>UGT1A1) and, to a lesser extent, to the pharmacologically active morphine-6-glucuronide (UGT2B7>UGT1A1). Concentrations may increase due to inhibition of UGT1A1 by erlotinib, but this effect is only established in vitro. Therefore, no clinically relevant effect on diamorphine exposure is expected. Additionally, morphine is a substrate of P-gp. Erlotinib does not inhibit or induce P-gp.

Description:

See summary

No Interaction Expected

Erlotinib

Diazepam

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Diazepam is metabolised to nordiazepam (by CYP3A4 and CYP2C19) and to temazepam (mainly by CYP3A4). Temazepam is mainly glucuronidated. Concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on diazepam exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Diclofenac

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Diclofenac is partly glucuronidated by UGT2B7 and partly oxidised by CYP2C9. Erlotinib does not inhibit or induce UGT2B7 or CYP2C9.

Description:

See summary

No Interaction Expected

Erlotinib

Digoxin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Digoxin is eliminated renally via the renal transporters OATP4C1 and P-gp. Erlotinib does not inhibit or induce OATP4C1 or P-gp.

Description:

See summary

No Interaction Expected

Erlotinib

Dihydrocodeine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dihydrocodeine undergoes predominantly direct glucuronidation, with CYP3A4 mediated metabolism accounting for only 5-10% of the overall metabolism. Concentrations may increase due to inhibition of CYP3A4 (moderate) and UGT1A1 by erlotinib. However, since CYP3A4 represents a minor pathway and UGT1A1 inhibition by erlotinib is only established in vitro, no clinically relevant effect on dihydrocodeine exposure is expected.

Description:

See summary

Potential Interaction

Erlotinib

Diltiazem

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Diltiazem is metabolised by CYP3A4 and CYP2D6. Concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on diltiazem exposure is expected. Diltiazem is also an inhibitor of CYP3A4 (moderate) and P-gp. However, the clinical relevance of P-gp inhibition by diltiazem is unknown. Erlotinib is metabolised by CYP3A4 (~70%) and concentrations may increase due to inhibition by diltiazem. After coadministration with ketoconazole, a strong CYP3A4 inhibitor, erlotinib exposure increased by 86%. A similar effect may occur after coadministration with diltiazem. Erlotinib is dosed at/near the maximum tolerated dose (MTD) and thus, any increase in erlotinib exposure may lead to toxicity. Coadministration should be approached with caution. If coadministration is unavoidable, reduce erlotinib dose by 50mg decrements. Monitor closely for erlotinib toxicity and, if available, erlotinib plasma concentrations.

Description:

See summary

No Interaction Expected

Erlotinib

Diphenhydramine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Diphenhydramine is mainly metabolised by CYP2D6 and to a lesser extent by CYPs 1A2, 2C9 and 2C19. Diphenhydramine is also a weak inhibitor of CYP2D6. Erlotinib does not interact with this metabolic pathway.

Description:

See summary

No Interaction Expected

Erlotinib

Dipyridamole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dipyridamole is glucuronidated by many UGTs, specifically those of the UGT1A subfamily. Concentrations may increase due to inhibition of UGT1A1 by erlotinib, but this effect is only established in vitro. Therefore, no clinically relevant effect on dipyridamole exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Disopyramide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Disopyramide is metabolised by CYP3A4 (25%) and 50% of the drug is eliminated unchanged in the urine. Concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on disopyramide exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Dolasetron

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dolasetron is converted by carbonyl reductase to its active metabolite, hydrodolasetron, which is mainly glucuronidated (60%) and metabolised by CYP2D6 (10-20%) and CYP3A4 (<1%). Concentrations may increase due to inhibition of CYP3A4 (moderate) and UGT1A1 by erlotinib. However, since CYP3A4 represents a minor pathway and UGT1A1 inhibition by erlotinib is only established in vitro, no clinically relevant effect on dolasetron exposure is expected. Erlotinib does not inhibit or induce CYP2D6.

Description:

See summary

No Interaction Expected

Erlotinib

Domperidone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Domperidone is mainly metabolised by CYP3A4 and concentrations may increase due to moderate inhibition by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on domperidone exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Dopamine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dopamine is metabolised in the liver, kidneys, and plasma by monoamine oxidase (MAO) and catechol-O-methyltransferase to inactive compounds. About 25% of a dose of dopamine is metabolised to norepinephrine within the adrenergic nerve terminals. There is little potential for dopamine to affect disposition of erlotinib, or to be affected if co-administered with erlotinib.

Description:

See summary

No Interaction Expected

Erlotinib

Doxazosin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Doxazosin is metabolised mainly by CYP3A4 and concentrations may increase due to moderate inhibition by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on doxazosin exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Doxepin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Doxepin is metabolised to nordoxepin (a metabolite with comparable pharmacological activity as the parent compound) mainly by CYP2C19. In addition, doxepin and nordoxepin are metabolised by CYP2D6. Erlotinib does not interact with this metabolic pathway.

Description:

See summary

No Interaction Expected

Erlotinib

Doxycycline

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Doxycycline is excreted in the urine and faeces as unchanged active substance, which is not affected by erlotinib. Between 40-60% of an administered dose can be accounted for in the urine.

Description:

See summary

No Interaction Expected

Erlotinib

Dronabinol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dronabinol is mainly metabolised by CYP2C9 and to a lesser extent by CYP3A4. Concentrations of dronabinol may alter due to moderate inhibition of CYP3A4 by erlotinib. However, since CYP3A4 represents a minor pathway no clinically relevant effect on dronabinol exposure is expected. Erlotinib does not inhibit or induce CYP2C9.

Description:

See summary

No Interaction Expected

Erlotinib

Drospirenone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Drospirenone is metabolised to a minor extent via CYP3A4 and concentrations may increase due to moderate inhibition by erlotinib. However, since CYP3A4 represents a minor pathway no clinically relevant effect on drospirnone exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Dulaglutide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dulaglutide is degraded by endogenous endopeptidases. Erlotinib does not interact with this metabolic pathway. Dulaglutide delays gastric emptying and could possibly decrease the absorption rate of concomitantly administered oral drugs. The clinical relevance of delayed absorption is considered to be limited.

Description:

See summary

No Interaction Expected

Erlotinib

Duloxetine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Duloxetine is metabolised by CYP2D6 and CYP1A2. Erlotinib does not inhibit or induce CYP2D6 or CYP1A2.

Description:

See summary

No Interaction Expected

Erlotinib

Dutasteride

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dutasteride is mainly metabolised by CYP3A4 and concentrations may increase due to moderate inhibition by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on dutasteride exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Dydrogesterone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dydrogesterone is metabolised to dihydrodydrogesterone (possibly via CYP3A4). Concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on dydrogesterone exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Edoxaban

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Edoxaban is partially metabolised by CYP3A4 (<10%) and is transported via P-gp. Concentrations of edoxaban may alter due to moderate inhibition of CYP3A4 by erlotinib. However, since CYP3A4 represents a minor pathway no clinically relevant effect on edoxaban exposure is expected. Erlotinib does not inhibit or induce P-gp.

Description:

See summary

No Interaction Expected

Erlotinib

Eltrombopag

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Eltrombopag is metabolised by cleavage conjugation (via UGT1A1 and UGT1A3) and oxidation (via CYP1A2 and CYP2C8). Concentrations may increase due to inhibition of UGT1A1 by erlotinib, but this effect is only established in vitro. Therefore, no clinically relevant effect on eltrombopag exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Enalapril

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Enalapril is hydrolysed to enalaprilat which is eliminated renally (possibly via OATs). Erlotinib is unlikely to interfere with this elimination pathway and does not inhibit or induce OATs.

Description:

See summary

No Interaction Expected

Erlotinib

Enoxaparin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Enoxaparin does not undergo cytochrome metabolism but is desulphated and depolymerised in the liver, and is predominantly renally excreted. Erlotinib is unlikely to interfere with this elimination pathway.

Description:

See summary

No Interaction Expected

Erlotinib

Eprosartan

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Eprosartan is largely excreted in bile and urine as unchanged drug. Erlotinib is unlikely to interfere with this elimination pathway.

Description:

See summary

No Interaction Expected

Erlotinib

Ertapenem

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ertapenem is mainly eliminated through the kidneys by glomerular filtration with tubular secretion playing a minor role. Erlotinib is unlikely to interfere with this elimination pathway.

Description:

See summary

Potential Interaction

Erlotinib

Erythromycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Erythromycin is a substrate of CYP3A4 and P-gp. Concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on erythromycin exposure is expected. Erythromycin is also an inhibitor of CYP3A4 (moderate) and P-gp. Erlotinib is metabolised by CYP3A4 (~70%) and concentrations may increase due to inhibition by erythromycin. After coadministration with ketoconazole, a strong CYP3A4 inhibitor, erlotinib exposure increased by 86%. A similar effect may occur after coadministration with erythromycin. Erlotinib is dosed at/near the maximum tolerated dose (MTD) and thus, any increase in erlotinib exposure may lead to toxicity. Coadministration should be approached with caution. If coadministration is unavoidable, reduce erlotinib dose by 50mg decrements. Monitor closely for erlotinib toxicity and, if available, erlotinib plasma concentrations.

Description:

See summary

No Interaction Expected

Erlotinib

Escitalopram

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Escitalopram is metabolised by CYPs 2C19 (37%), 2D6 (28%) and 3A4 (35%) to form N-desmethylescitalopram. Concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on escitalopram exposure is expected.

Description:

See summary

Potential Weak Interaction

Erlotinib

Esomeprazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Esomeprazole is metabolised by CYP2C19 and CYP3A4. Concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on esomeprazole exposure is expected. Esomeprazole is also an inhibitor of CYP2C19. Erlotinib is not metabolised by CYP2C19. Moreover, the bioavailability of erlotinib is pH-dependent and, thus, an increase in gastric pH by esomeprazole reduces its bioavailability. Results on whether this decrease in exposure will lead to a decreased efficacy of erlotinib are conflicting. If coadministration is clinically necessary, erlotinib should be administered at the moment at which acid secretion is less inhibited, and that is just before a new dose of esomeprazole. Furthermore, erlotinib may be administered concomitantly with an acidic beverage like cola, to overcome decreased bioavailability.

Description:

See summary

No Interaction Expected

Erlotinib

Estazolam

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Estazolam is metabolised to its major metabolite 4-hydroxyestazolam via CYP3A4 and concentrations may increase due to moderate inhibition by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on estazolam exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Estradiol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Estradiol is metabolised by CYP3A4, CYP1A2 and is glucuronidated. Concentrations may increase due to inhibition of CYP3A4 (moderate) and UGT1A1 by erlotinib. However, since CYP3A4 represents a minor pathway and UGT1A1 inhibition by erlotinib is only established in vitro, no clinically relevant effect on estradiol exposure is expected. Erlotinib does not inhibit or induce CYP1A2.

Description:

See summary

No Interaction Expected

Erlotinib

Ethambutol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ethambutol is partly metabolised by alcohol dehydrogenase (20%) and partly eliminated unchanged in the faeces (20%) and urine (50%). Erlotinib is unlikely to interfere with this metabolic or elimination pathway.

Description:

See summary

No Interaction Expected

Erlotinib

Ethinylestradiol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ethinylestradiol undergoes oxidation (CYP3A4>CYP2C9), sulfation and glucuronidation (UGT1A1). Concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Concentrations may also increase due to inhibition of UGT1A1 by erlotinib, but this effect is only established in vitro. Therefore, no clinically relevant effect on ethinylestradiol exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Ethionamide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ethionamide is extensively metabolised in the liver; animal studies suggest involvement of flavin-containing monooxygenases. Erlotinib does not interact with this metabolic pathway.

Description:

See summary

No Interaction Expected

Erlotinib

Etonogestrel

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Etonogestrel is metabolised by CYP3A4 and concentrations may increase due to moderate inhibition by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on etonogestrel exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Everolimus (Immunosuppressant)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Everolimus is mainly metabolised by CYP3A4 and is a substrate of P-gp. Concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on everolimus exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Exenatide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Exenatide is cleared mainly by glomerular filtration. Erlotinib is unlikely to interfere with this elimination pathway. Exenatide delays gastric emptying and could possibly decrease the absorption rate of concomitantly administered oral drugs. The clinical relevance of delayed absorption is considered to be limited.

Description:

See summary

No Interaction Expected

Erlotinib

Ezetimibe

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ezetimibe is glucuronidated by UGTs 1A1 and 1A3 and to a lesser extent by UGTs 2B15 and 2B7. Concentrations may increase due to inhibition of UGT1A1 by erlotinib, but this effect is only established in vitro. Therefore, no clinically relevant effect on ezetimibe exposure is expected.

Description:

See summary

Potential Weak Interaction

Erlotinib

Famotidine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Famotidine is excreted via OAT1/OAT3. Erlotinib does not inhibit or induce OATs. However, the bioavailability of erlotinib is pH-dependent and, thus, an increase in gastric pH by famotidine reduces its bioavailability. Results whether this decrease in exposure will lead to a decreased efficacy of erlotinib are conflicting. If coadministration is clinically necessary, erlotinib should be administered at the moment at which acid secretion is less inhibited, and that is just before a new dose of famotidine. Furthermore, erlotinib may be administered concomitantly with an acidic beverage like cola, to overcome decreased bioavailability.

Description:

See summary

No Interaction Expected

Erlotinib

Felodipine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Felodipine is metabolised by CYP3A4 and concentrations may increase due to moderate inhibition by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on felodipine exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Fenofibrate

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fenofibrate is hydrolysed to an active metabolite, fenofibric acid. In vitro data suggest that fenofibric acid inhibits OAT3. Erlotinib does not interact with this metabolic pathway.

Description:

See summary

No Interaction Expected

Erlotinib

Fentanyl

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fentanyl undergoes extensive CYP3A4 metabolism and concentrations may increase due to moderate inhibition of by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on fentanyl exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Fexofenadine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fexofenadine is a substrate of P-gp. Erlotinib does not inhibit or induce P-gp.

Description:

See summary

No Interaction Expected

Erlotinib

Finasteride

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Finasteride is metabolised by CYP3A4 and concentrations may increase due to moderate inhibition by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on finasteride exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Fish oils

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely.

Description:

See summary

No Interaction Expected

Erlotinib

Flecainide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Flecainide is metabolised mainly via CYP2D6, with a proportion (approximately 30%) of the parent drug also eliminated unchanged renally. Erlotinib does not inhibit or induce CYP2D6 and is unlikely to interfere with this elimination pathway.

Description:

See summary

Potential Weak Interaction

Erlotinib

Flucloxacillin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Flucloxacillin is mainly renally eliminated partly by glomerular filtration and partly by active secretion via OAT1. Flucloxacillin is described as a CYP3A4 inducer. The mechanism and clinical relevance of this interaction is unknown. However, erlotinib concentrations may decrease due to CYP3A4 induction by flucloxacillin. Monitor erlotinib plasma concentrations, if available.

Description:

See summary

Potential Interaction

Erlotinib

Fluconazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Fluconazole is cleared primarily by renal excretion and is also an inhibitor of CYPs 3A4 (moderate), 2C9 (moderate) and 2C19 (strong). Erlotinib is metabolised by CYP3A4 (~70%) and concentrations may increase due to inhibition by fluconazole. After coadministration with ketoconazole, a strong CYP3A4 inhibitor, erlotinib exposure increased by 86%. A similar effect may occur after coadministration with fluconazole. Erlotinib is dosed at/near the maximum tolerated dose (MTD) and thus, any increase in erlotinib exposure may lead to toxicity. Coadministration should be approached with caution. If coadministration is unavoidable, reduce erlotinib dose by 50mg decrements. Monitor closely for erlotinib toxicity and, if available, erlotinib plasma concentrations.

Description:

See summary

No Interaction Expected

Erlotinib

Flucytosine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Flucytosine is metabolised to 5-fluorouracil (5-FU). 5-FU is further metabolised by dihydropyrimidine dehydrogenase (DPD) to an inactive metabolite. Erlotinib does not interact with this metabolic pathway.

Description:

See summary

No Interaction Expected

Erlotinib

Fludrocortisone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fludrocortisone is metabolised in the liver to inactive metabolites, possibly via CYP3A. Concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on fludrocortisone exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Flunitrazepam

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Flunitrazepam is metabolised mainly via CYP3A4 and CYP2C19. Concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on flunitrazepam exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Fluoxetine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fluoxetine is mainly metabolised by CYP2D6 and CYP2C9 and to a lesser extent by CYP2C19 and CYP3A4 to form norfluoxetine. Concentrations of fluoxetine may alter due to moderate inhibition of CYP3A4 by erlotinib. However, since CYP3A4 represents a minor pathway no clinically relevant effect on fluoxetine exposure is expected. Erlotinib does not inhibit or induce CYPs 2D6, 2C9 or 2C19. Fluoxetine is also a strong inhibitor of CYP2D6 and CYP2C19, which does not affect erlotinib.

Description:

See summary

No Interaction Expected

Erlotinib

Fluphenazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fluphenazine is metabolised by CYP2D6. Erlotinib does not inhibit or induce CYP2D6.

Description:

See summary

No Interaction Expected

Erlotinib

Flurazepam

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. The metabolism of flurazepam is most likely CYP-mediated. Concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on flurazepam exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Fluticasone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fluticasone is metabolised by CYP3A4 and concentrations may increase due to moderate inhibition by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on fluticasone exposure is expected. Note: A clinically significant interaction is also unlikely with the topical use of fluticasone.

Description:

See summary

No Interaction Expected

Erlotinib

Fluvastatin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fluvastatin is mainly metabolised by CYP2C9 (75%) and to a lesser extent by CYP3A4 (20%) and CYP2C8 (5%). Concentrations of fluvastatin may alter due to moderate inhibition of CYP3A4 and CYP2C8 by erlotinib. However, since both represent minor pathways no clinically relevant effect on fluvastatin exposure is expected. Erlotinib does not inhibit or induce CYP2C9. Fluvastatin also potentially inhibits CYP2C9. Erlotinib is not metabolised by CYP2C9.

Description:

See summary

Potential Interaction

Erlotinib

Fluvoxamine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Fluvoxamine is metabolised mainly by CYP2D6 and to a lesser extent by CYP1A2. Erlotinib does not inhibit or induce CYP2D6 or CYP1A2. Fluvoxamine is also an inhibitor of CYPs 1A2 (strong), 2C19 (strong), 3A4 (moderate), 2C9 (weak-moderate) and CYP2D6 (weak). Erlotinib is metabolised by CYP3A4 (~70%) and concentrations may increase due to inhibition by fluvoxamine. After coadministration with ketoconazole, a strong CYP3A4 inhibitor, erlotinib exposure increased by 86%. A similar effect may occur after coadministration with fluvoxamine. Erlotinib is dosed at/near the maximum tolerated dose (MTD) and thus, any increase in erlotinib exposure may lead to toxicity. Coadministration should be approached with caution. If coadministration is unavoidable, reduce erlotinib dose by 50mg decrements. Monitor closely for erlotinib toxicity and, if available, erlotinib plasma concentrations.

Description:

See summary

No Interaction Expected

Erlotinib

Fondaparinux

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fondaparinux does not undergo cytochrome metabolism but is eliminated predominantly renally. Erlotinib is unlikely to interfere with this elimination pathway.

Description:

See summary

No Interaction Expected

Erlotinib

Formoterol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Formoterol is eliminated primarily by direct glucuronidation, with O-demethylation (by CYPs 2D6, 2C19, 2C9, and 2A6) followed by further glucuronidation. As multiple CYP450 and UGT enzymes catalyse the transformation the potential for a pharmacokinetic interaction is low.

Description:

See summary

Potential Interaction

Erlotinib

Fosaprepitant

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Fosaprepitant is rapidly, almost completely, converted to the active metabolite aprepitant. Erlotinib does not interact with this metabolic pathway. Aprepitant is mainly metabolized by CYP3A4 and to a lesser extent by CYP1A2 and CYP2C19. Concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on aprepitant exposure is expected. During treatment aprepitant is a moderate inhibitor of CYP3A4. Moreover, after treatment aprepitant is a weak inducer of CYP3A4, CYP2C9 and UGT. Erlotinib is metabolised by CYP3A4 (~70%) and concentrations may increase due to inhibition by aprepitant during treatment. After coadministration with ketoconazole, a strong CYP3A4 inhibitor, erlotinib exposure increased by 86%. A similar effect may occur after coadministration with aprepitant. Erlotinib is dosed at/near the maximum tolerated dose (MTD) and thus, any increase in erlotinib exposure may lead to toxicity. Coadministration should be approached with caution. If coadministration is unavoidable, reduce erlotinib dose by 50mg decrements. Monitor closely for erlotinib toxicity and, if available, erlotinib plasma concentrations.

Description:

See summary

Do Not Coadminister

Erlotinib

Fosphenytoin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is contraindicated. Fosphenytoin is rapidly converted to the active metabolite phenytoin. Phenytoin is mainly metabolized by CYP2C9 and to a lesser extent by CYP2C19. Erlotinib does not inhibit or induce CYP2C9 or CYP2C19. Phenytoin is also a potent inducer of CYP3A4, UGT and P-gp. Erlotinib is metabolised by CYP3A4 (~70%) and concentrations may decrease due to induction by fosphenytoin. After coadministration with rifampicin, a strong CYP3A4 inducer, erlotinib exposure decreased by 69%. A similar effect may occur after coadministration with fosphenytoin, although the magnitude and relevancy of the effect are unknown. Avoid concomitant use. If coadministration is unavoidable, increase erlotinib dosage by 50mg at 2-week intervals to a maximum of 450mg as tolerated. Monitor erlotinib plasma concentrations, if available.

Description:

See summary

No Interaction Expected

Erlotinib

Furosemide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Furosemide is glucuronidated mainly in the kidney (UGT1A9) and to a lesser extent in the liver (UGT1A1). Concentrations may increase due to inhibition of UGT1A1 by erlotinib, but this effect is only established in vitro. Therefore, no clinically relevant effect on furosemide exposure is expected. A large proportion of furosemide is also eliminated unchanged renally (via OATs). OAT1/3 are the major transporters of loop and thiazide diuretics. Secretion of these diuretics into the urinary tract by transporters in the proximal tubular cells is necessary for the diuretic effect in later tubule segments. In vitro data indicate that furosemide is also an inhibitor of the renal transporters OAT1/OAT3. Erlotinib is unlikely to interfere with this metabolic or elimination pathway.

Description:

See summary

No Interaction Expected

Erlotinib

Gabapentin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Gabapentin is cleared mainly by glomerular filtration. Erlotinib is unlikely to interfere with this elimination pathway.

Description:

See summary

No Interaction Expected

Erlotinib

Gemfibrozil

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Gemfibrozil is metabolised by UGT2B7. Gemfibrozil is also an inhibitor of CYP2C8 (strong), OATP1B1 and OAT3. In vitro data indicate gemfibrozil to be a strong inhibitor of CYP2C9 but in vivo data showed no relevant effect on CYP2C9. Erlotinib does not interact with this metabolic pathway.

Description:

See summary

No Interaction Expected

Erlotinib

Gentamicin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Gentamicin is eliminated unchanged predominantly via glomerular filtration. Erlotinib is unlikely to interfere with this elimination pathway.

Description:

See summary

No Interaction Expected

Erlotinib

Gestodene

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Gestodene is metabolised by CYP3A4 and to a lesser extent by CYP2C9 and CYP2C19. Concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on gestodene exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Glibenclamide (Glyburide)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Glibenclamide is mainly metabolised by CYP3A4 and to a lesser extent by CYP2C9. Concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on glibenclamide exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Gliclazide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Gliclazide is metabolised mainly by CYP2C9 and to a lesser extent by CYP2C19. Erlotinib does not inhibit or induce CYP2C9 or CYP2C19.

Description:

See summary

No Interaction Expected

Erlotinib

Glimepiride

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Glimepiride is mainly metabolised by CYP2C9. Erlotinib does not inhibit or induce CYP2C9.

Description:

See summary

No Interaction Expected

Erlotinib

Glipizide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Glipizide is mainly metabolised by CYP2C9. Erlotinib does not inhibit or induce CYP2C9.

Description:

See summary

No Interaction Expected

Erlotinib

Granisetron

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Granisetron is metabolised by CYP3A4 and is a substrate of P-gp. Concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on granisetron exposure is expected.

Description:

See summary

Do Not Coadminister

Erlotinib

Grapefruit juice

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is contraindicated. Grapefruit juice is known to inhibit CYP3A4 enzymes. Erlotinib is metabolised by CYP3A4 (~70%) and concentrations may increase due to inhibition by grapefruit juice. After coadministration with ketoconazole, a strong CYP3A4 inhibitor, erlotinib exposure increased by 86%. A similar effect may occur after coadministration with grapefruit juice. Erlotinib is dosed at/near the maximum tolerated dose (MTD) and thus, any increase in erlotinib exposure may lead to toxicity. Therefore, co-administration should be avoided.

Description:

See summary

No Interaction Expected

Erlotinib

Green tea

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely.

Description:

See summary

Potential Interaction

Erlotinib

Griseofulvin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Less than 1% of a griseofulvin dose is excreted unchanged via the kidneys. Griseofulvin is also a liver microsomal enzyme inducer and may lower plasma levels, and therefore reduce the efficacy of concomitantly administered medicinal products that are metabolised by CYPs, such as erlotinib. If coadministration is unavoidable, increase erlotinib dosage by 50mg at 2-week intervals to a maximum of 450mg as tolerated. Monitor erlotinib plasma concentrations, if available.

Description:

See summary

No Interaction Expected

Erlotinib

Haloperidol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Haloperidol has a complex metabolism as it undergoes glucuronidation (UGTs 2B7>1A4, 1A9), carbonyl reduction as well as oxidative metabolism (CYP3A4 and CYP2D6). Concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on haloperidol exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Heparin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Heparin is thought to be eliminated via the reticuloendothelial system. Erlotinib is unlikely to interfere with this elimination pathway.

Description:

See summary

Potential Interaction

Erlotinib

Hydralazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Hydralazine is metabolised via primary oxidative metabolism and acetylation. Erlotinib does not interact with this metabolic pathway. In vitro studies have suggested that hydralazine is a mixed enzyme inhibitor, which may weakly inhibit CYP3A4 and CYP2D6. Erlotinib is metabolised by CYP3A4 (~70%) and concentrations may increase due to inhibition by hydralazine. After coadministration with ketoconazole, a strong CYP3A4 inhibitor, erlotinib exposure increased by 86%. A similar effect may occur after coadministration with hydralazine. Erlotinib is dosed at/near the maximum tolerated dose (MTD) and thus, any increase in erlotinib exposure may lead to toxicity. Coadministration should be approached with caution. If coadministration is unavoidable, reduce erlotinib dose by 50mg decrements. Monitor closely for erlotinib toxicity and, if available, erlotinib plasma concentrations.

Description:

See summary

No Interaction Expected

Erlotinib

Hydrochlorothiazide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Hydrochlorothiazide is not metabolised and is cleared by the kidneys via OAT1. OAT1/3 are the major transporters of loop and thiazide diuretics. Secretion of these diuretics into the urinary tract by transporters in the proximal tubular cells is necessary for the diuretic effect in later tubule segments. Erlotinib does not inhibit or induce OATs.

Description:

See summary

No Interaction Expected

Erlotinib

Hydrocodone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Hydrocodone is metabolised by CYP2D6 to hydromorphone and by CYP3A4 to norhydrocodone, both of which have analgesic effects. Concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on hydrocodone exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Hydrocortisone (oral)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Hydrocortisone is metabolised by CYP3A4 and concentrations may increase due to moderate inhibition by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on hydrocortisone (oral) exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Hydrocortisone (topical)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely with the topical use of hydrocortisone.

Description:

See summary

No Interaction Expected

Erlotinib

Hydromorphone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Hydromorphone is eliminated via glucuronidation, mainly by UGT2B7. Erlotinib does not inhibit or induce UGT2B7.

Description:

See summary

No Interaction Expected

Erlotinib

Hydroxyurea (Hydroxycarbamide)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Hydroxyurea is metabolised in the liver and cleared via the lungs and kidneys. Erlotinib is unlikely to interfere with this metabolic or elimination pathway.

Description:

See summary

No Interaction Expected

Erlotinib

Hydroxyzine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Hydroxyzine is partly metabolised by alcohol dehydrogenase and partly by CYP3A4. Concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on hydroxyzine exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Ibandronic acid

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ibandronic acid is not metabolised and is cleared from the plasma by uptake into bone and elimination via renal excretion. Although no pharmacokinetic interaction is expected, ibandronic acid should be taken after an overnight fast (at least 6 hours) and before the first food or drink of the day. Medicinal products and supplements should be similarly avoided prior to taking ibandronic acid. Fasting should be continued for at least 30 minutes after taking ibandronic acid.

Description:

See summary

No Interaction Expected

Erlotinib

Ibuprofen

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ibuprofen is metabolised mainly by CYP2C9 and to a lesser extent by CYP2C8 and direct glucuronidation. Concentrations may increase due to moderate inhibition of CYP2C8 by erlotinib, but this effect is only established in vitro. Moreover, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on ibuprofen exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Iloperidone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Iloperidone is metabolised by CYP3A4 and CYP2D6. Concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on iloperidone exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Imipenem/Cilastatin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Imipenem/cilastatin are eliminated by glomerular filtration and to a lesser extent by active tubular secretion. Erlotinib is unlikely to interfere with this elimination pathway.

Description:

See summary

No Interaction Expected

Erlotinib

Imipramine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Imipramine is metabolised by CYPs 3A4, 2C19 and 1A2 to desipramine. Concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on imipramine exposure is expected. Imipramine and desipramine are both metabolised by CYP2D6. Erlotinib does not inhibit or induce CYP2D6.

Description:

See summary

No Interaction Expected

Erlotinib

Indapamide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Indapamide is extensively metabolised by CYP450s. Concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on indapamide exposure is expected. OAT1/3 are the major transporters of loop and thiazide diuretics, which are not affected by erlotinib. Secretion of these diuretics into the urinary tract by transporters in the proximal tubular cells is necessary for the diuretic effect in later tubule segments. Erlotinib does not inhibit or induce OATs.

Description:

See summary

No Interaction Expected

Erlotinib

Insulin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely.

Description:

See summary

No Interaction Expected

Erlotinib

Interferon alpha

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely.

Description:

See summary

No Interaction Expected

Erlotinib

Interleukin 2 (Aldesleukin)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Interleukin-2 is mainly eliminated by glomerular filtration. Erlotinib is unlikely to interfere with this elimination pathway.

Description:

See summary

No Interaction Expected

Erlotinib

Ipratropium bromide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. A small proportion of an inhaled ipratropium dose is systemically absorbed (6.9%). Metabolism is via ester hydrolysis and conjugation. Erlotinib does not interact with this metabolic pathway.

Description:

See summary

No Interaction Expected

Erlotinib

Irbesartan

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Irbesartan is metabolised by glucuronidation and oxidation (mainly CYP2C9). Erlotinib does not interact with this metabolic pathway.

Description:

See summary

No Interaction Expected

Erlotinib

Iron supplements

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely.

Description:

See summary

No Interaction Expected

Erlotinib

Isoniazid

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Isoniazid is acetylated in the liver to form acetylisoniazid which is then hydrolysed to isonicotinic acid and acetylhydrazine. Erlotinib does not interact with this metabolic pathway.

Description:

See summary

No Interaction Expected

Erlotinib

Isosorbide dinitrate

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. In vitro studies suggest that CYP3A4 has a role in nitric oxide formation from isosorbide dinitrate and concentrations may increase due to moderate inhibition of by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on isosorbide dinitrate exposure is expected.

Description:

See summary

Potential Interaction

Erlotinib

Itraconazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Itraconazole is primarily metabolised by CYP3A4 and is also an inhibitor of CYP3A4 (strong), CYP2C9 (weak), P-gp and BCRP. Concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on itraconazole exposure is expected. Moreover, erlotinib is metabolised by CYP3A4 (~70%) and concentrations may increase due to inhibition by itraconazole. After coadministration with ketoconazole, a strong CYP3A4 inhibitor, erlotinib exposure increased by 86%. A similar effect may occur after coadministration with itraconazole. Erlotinib is dosed at/near the maximum tolerated dose (MTD) and thus, any increase in erlotinib exposure may lead to toxicity. Coadministration should be approached with caution. If coadministration is unavoidable, reduce erlotinib dose by 50mg decrements. Monitor closely for erlotinib toxicity and plasma concentrations, if available

Description:

See summary

No Interaction Expected

Erlotinib

Ivabradine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ivabradine is metabolised by CYP3A4 and concentrations may increase due to moderate inhibition by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on ivabradine exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Kanamycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Kanamycin is eliminated unchanged predominantly via glomerular filtration. Erlotinib is unlikely to interfere with this elimination pathway.

Description:

See summary

Potential Interaction

Erlotinib

Ketoconazole

Quality of Evidence: Low

Summary:

Coadministration has been studied and should be approached with caution. Ketoconazole is a substrate of CYP3A4 and concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on ketoconazole exposure is expected. Moreover, ketoconazole is an inhibitor of CYP3A4 (strong) and P-gp. Erlotinib is metabolised by CYP3A4 (~70%) and concentrations will increase due to inhibition by ketoconazole. In healthy subjects (n=12), coadministration of erlotinib (100 mg single dose) and ketoconazole (200 mg twice daily for 5 days) increased erlotinib exposure by 86%, relative to erlotinib only. Erlotinib is dosed at/near the maximum tolerated dose (MTD) and thus, any increase in erlotinib exposure may lead to toxicity. Coadministration should be approached with caution. If coadministration is unavoidable, reduce erlotinib dose by 50mg decrements. Monitor closely for erlotinib toxicity and, if available, erlotinib plasma concentrations.

Description:

See summary

No Interaction Expected

Erlotinib

Labetalol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Labetalol is mainly glucuronidated (via UGT1A1 and UGT2B7). Concentrations may increase due to inhibition of UGT1A1 by erlotinib, but this effect is only established in vitro. Therefore, no clinically relevant effect on labetalol exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Lacidipine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lacidipine is metabolised by CYP3A4 and concentrations may increase due to moderate inhibition by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on lacidipine exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Lactulose

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metabolism of lactulose to lactic acid occurs via gastro-intestinal microbial flora only. Erlotinib does not interact with this metabolic pathway.

Description:

See summary

Potential Weak Interaction

Erlotinib

Lansoprazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Lansoprazole is mainly metabolised by CYP2C19 and to a lesser extent by CYP3A4. Concentrations of lansoprazole may alter due to moderate inhibition of CYP3A4 by erlotinib. However, since CYP3A4 represents a minor pathway no clinically relevant effect on lansoprazole exposure is expected. Erlotinib does not inhibit or induce CYP2C19. Moreover, the bioavailability of erlotinib is pH-dependent and, thus, an increase in gastric pH by lansoprazole reduces its bioavailability. Results on whether this decrease in exposure will lead to a decreased efficacy of erlotinib are conflicting. If coadministration is clinically necessary, erlotinib should be administered at the moment at which acid secretion is less inhibited, and that is just before a new dose of lansoprazole. Furthermore, erlotinib may be administered concomitantly with an acidic beverage like cola, to overcome decreased bioavailability.

Description:

See summary

No Interaction Expected

Erlotinib

Lercanidipine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lercanidipine is mainly metabolised by CYP3A4 and concentrations may increase due to moderate inhibition by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on lercanidipine exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Levocetirizine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Less than 14% of a dose of levocetirizine is metabolised. Levocetirizine is mainly eliminated unchanged in the urine through both glomerular filtration and tubular secretion. Erlotinib is unlikely to interfere with this elimination pathway.

Description:

See summary

No Interaction Expected

Erlotinib

Levofloxacin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Levofloxacin is renally eliminated mainly by glomerular filtration and active secretion (possibly OCT2). Erlotinib is unlikely to interfere with this elimination pathway and does not inhibit or induce OCT2.

Description:

See summary

No Interaction Expected

Erlotinib

Levomepromazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Levomepromazine is metabolised by CYP2D6. Erlotinib does not inhibit or induce CYP2D6.

Description:

See summary

No Interaction Expected

Erlotinib

Levonorgestrel

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Levonorgestrel mainly is metabolised by CYP3A4 and is glucuronidated to a minor extent. Concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on levonorgestrel exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Levonorgestrel (Emergency Contraception)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Levonorgestrel is mainly metabolised by CYP3A4 and is glucuronidated to a minor extent. Concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on levonorgestrel exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Levothyroxine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Levothyroxine is metabolised by deiodination (by enzymes of deiodinase family) and glucuronidation. Erlotinib does not interact with this metabolic pathway.

Description:

See summary

No Interaction Expected

Erlotinib

Lidocaine (Lignocaine)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. CYP1A2 is the predominant enzyme involved in lidocaine metabolism in the range of therapeutic concentrations with a minor contribution from CYP3A4. Concentrations of lidocaine may alter due to moderate inhibition of CYP3A4 by erlotinib. However, since CYP3A4 represents a minor pathway no clinically relevant effect on lidocaine exposure is expected. Erlotinib does not inhibit or induce CYP1A2.

Description:

See summary

Potential Interaction

Erlotinib

Linagliptin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Linagliptin is mainly eliminated as parent compound in faeces with metabolism by CYP3A4 representing a minor elimination pathway. Concentrations of linagliptin may alter due to moderate inhibition of CYP3A4 by erlotinib. However, since CYP3A4 represents a minor pathway no clinically relevant effect on linagliptin exposure is expected. Linagliptin is also a substrate of P-gp and is a weak inhibitor of CYP3A4. Erlotinib is metabolised by CYP3A4 (~70%) and concentrations may increase due to inhibition by linagliptin. After coadministration with ketoconazole, a strong CYP3A4 inhibitor, erlotinib exposure increased by 86%. A similar effect may occur after coadministration with linagliptin. Erlotinib is dosed at/near the maximum tolerated dose (MTD) and thus, any increase in erlotinib exposure may lead to toxicity. Coadministration should be approached with caution. If coadministration is unavoidable, reduce erlotinib dose by 50mg decrements. Monitor closely for erlotinib toxicity and, if available, erlotinib plasma concentrations.

Description:

See summary

No Interaction Expected

Erlotinib

Linezolid

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Linezolid undergoes non-CYP mediated metabolism. Erlotinib is unlikely to interfere with this unspecified metabolic pathway.

Description:

See summary

No Interaction Expected

Erlotinib

Liraglutide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Liraglutide is degraded by endogenous endopeptidases. Erlotinib does not interact with this metabolic pathway.

Description:

See summary

No Interaction Expected

Erlotinib

Lisinopril

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lisinopril is eliminated unchanged renally via glomerular filtration. Erlotinib is unlikely to interfere with this elimination pathway.

Description:

See summary

No Interaction Expected

Erlotinib

Lithium

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lithium is mainly eliminated unchanged through the kidneys. Lithium is freely filtered at a rate that is dependent upon the glomerular filtration rate therefore no pharmacokinetic interaction is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Live vaccines

Quality of Evidence: Very Low

Summary:

Coadministration of live vaccines (such as BCG vaccine; measles, mumps and rubella vaccines; varicella vaccines; typhoid vaccines; rotavirus vaccines; yellow fever vaccines; oral polio vaccine) has not been studied. In patients, who are receiving cytotoxics or other immunosuppressant drugs, use of live vaccines for immunisation is contraindicated. However, since erlotinib is not an immunosuppressant drug, no additional unwanted effects are expected.

Description:

See summary

No Interaction Expected

Erlotinib

Loperamide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Loperamide is mainly metabolised by CYP3A4 and CYP2C8, and is a substrate of P-gp. Concentrations may increase due to inhibition of CYP3A4 (moderate, in vivo) and CYP2C8 (moderate, in vitro) by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on loperamide exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Loratadine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Loratadine is metabolised mainly by CYP3A4 and to a lesser extent by CYP2D6. Concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on loratadine exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Lorazepam

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lorazepam undergoes non-CYP-mediated elimination. Erlotinib is unlikely to interfere with this elimination pathway.

Description:

See summary

No Interaction Expected

Erlotinib

Lormetazepam

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lormetazepam is mainly glucuronidated and concentrations may increase due to inhibition of UGT1A1 by erlotinib, but this effect is only established in vitro. Therefore, no relevant effect on lormetazepam exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Losartan

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Losartan is converted to its active metabolite mainly by CYP2C9 in the range of clinical concentrations. Erlotinib does not inhibit or induce CYP2C9.

Description:

See summary

No Interaction Expected

Erlotinib

Lovastatin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lovastatin is metabolised by CYP3A4 and concentrations may increase due to moderate inhibition by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on lovastatin exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Macitentan

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Macitentan is metabolised mainly by CYP3A4 and to a lesser extent by CYPs 2C19, 2C9 and 2C8. Concentrations may increase due to moderate inhibition of CYP3A4 and CYP2C8 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on macitentan exposure is expected.

Description:

See summary

Potential Weak Interaction

Erlotinib

Magnesium

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Magnesium is eliminated in the kidney, mainly by glomerular filtration. Erlotinib is unlikely to interfere with this elimination pathway. However, the bioavailability of erlotinib is pH-dependent and, thus, an increase in gastric pH by magnesium reduces its bioavailability. Results on whether this decrease in exposure will lead to a decreased efficacy of erlotinib are conflicting. If coadministration is clinically necessary, erlotinib should be administered at the moment at which antacid action is unlikely, and that is just before a new dose of magnesium.

Description:

See summary

No Interaction Expected

Erlotinib

Maprotiline

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Maprotiline is mainly metabolised by CYP2D6. Erlotinib does not inhibit or induce CYP2D6.

Description:

See summary

No Interaction Expected

Erlotinib

Medroxyprogesterone (depot)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Medroxyprogesterone is metabolised by CYP3A4 and concentrations may increase due to moderate inhibition by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on medroxyprogesterone exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Medroxyprogesterone (non-depot)

Quality of Evidence: Very Low

Summary:

Description:

See summary

No Interaction Expected

Erlotinib

Mefenamic acid

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Mefenamic acid is metabolised by CYP2C9 and glucuronidated by UGT2B7 and UGT1A9. Erlotinib does not inhibit or induce CYP2C9, UGT2B7 or UGT1A9.

Description:

See summary

No Interaction Expected

Erlotinib

Megestrol acetate

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Megestrol acetate is mainly eliminated in the urine. Erlotinib is unlikely to interfere with this elimination pathway.

Description:

See summary

No Interaction Expected

Erlotinib

Meropenem

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Meropenem is primarily eliminated by the kidney with in vitro data suggesting it is a substrate of the renal transporters OAT3>OAT1. Erlotinib is unlikely to interfere with this elimination pathway and does not inhibit or induce OATs.

Description:

See summary

No Interaction Expected

Erlotinib

Mesalazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Mesalazine is metabolised to N-acetyl-mesalazine by N-acetyltransferase. Erlotinib does not interact with this metabolic pathway.

Description:

See summary

Do Not Coadminister

Erlotinib

Metamizole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is contraindicated. Metamizole is metabolised by hydrolysis to the active metabolite MAA in the gastrointestinal tract. Erlotinib does not interact with this metabolic pathway. Metamizole is metabolised in serum and excreted via urine (90%) and faeces (10%). Metamizole is an inducer of CYP3A4. Erlotinib is metabolised by CYP3A4 (~70%) and concentrations may decrease due to induction by metamizole. After coadministration with rifampicin, a strong CYP3A4 inducer, erlotinib exposure decreased by 69%. A similar effect may occur after coadministration with metamizole, although the magnitude and relevancy of the effect are unknown. Avoid concomitant use. If coadministration is unavoidable, increase erlotinib dosage by 50mg at 2-week intervals to a maximum of 450mg as tolerated. Monitor erlotinib plasma concentrations, if available.

Description:

See summary

No Interaction Expected

Erlotinib

Metformin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metformin is mainly eliminated unchanged in the urine and is substrate of OCT1, OCT2, OCT3, MATE1 and MATE2K. Erlotinib is unlikely to interfere with this elimination pathway and does not inhibit or induce OCTs or MATEs.

Description:

See summary

No Interaction Expected

Erlotinib

Methadone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Methadone is demethylated by CYP3A4 and concentrations may increase due to moderate inhibition by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on methadone exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Methyldopa

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Methyldopa is excreted in urine largely by glomerular filtration, primarily unchanged and as the mono-O-sulfate conjugate. Erlotinib is unlikely to interfere with this elimination pathway.

Description:

See summary

No Interaction Expected

Erlotinib

Methylphenidate

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Methylphenidate is not metabolised by CYP450s to a relevant extent and does not inhibit or induce CYP450s. Therefore, there is little potential for methylphenidate to affect disposition of erlotinib, or to be affected if co-administered with erlotinib.

Description:

See summary

No Interaction Expected

Erlotinib

Methylprednisolone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Methylprednisolone is metabolised by CYP3A4 and concentrations may increase due to moderate inhibition by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on methylprednisolone exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Metoclopramide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metoclopramide is partially metabolised by CYP450 system (mainly CYP2D6). Erlotinib does not inhibit or induce CYP2D6.

Description:

See summary

No Interaction Expected

Erlotinib

Metolazone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metolazone is largely excreted unchanged in the urine. OAT1/3 are the major transporters of loop and thiazide diuretics, which are not affected by erlotinib. Secretion of these diuretics into the urinary tract by transporters in the proximal tubular cells is necessary for the diuretic effect in later tubule segments. Erlotinib is unlikely to interfere with this elimination pathway and does not inhibit or induce OATs.

Description:

See summary

No Interaction Expected

Erlotinib

Metoprolol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metoprolol is mainly metabolised by CYP2D6. Erlotinib does not inhibit or induce CYP2D6.

Description:

See summary

No Interaction Expected

Erlotinib

Metronidazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metronidazole is eliminated via glomerular filtration. Erlotinib is unlikely to interfere with this elimination pathway. Elevated plasma concentrations have been reported for some CYP3A substrates (e.g. tacrolimus, ciclosporin) with metronidazole. Erlotinib is metabolised by CYP3A4. However, metronidazole did not increase concentrations of several CYP3A probe drugs (e.g. midazolam, alprazolam). Therefore, no clinically relevant effect on erlotinib exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Mexiletine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Mexiletine is metabolised mainly by CYP2D6 and to a lesser extent CYP1A2. Erlotinib does not inhibit or induce CYP2D6 or CYP1A2.

Description:

See summary

No Interaction Expected

Erlotinib

Mianserin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Mianserin is metabolised by CYPs 2D6 and 1A2, and to a lesser extent by CYP3A4. Concentrations of mianserin may alter due to moderate inhibition of CYP3A4 by erlotinib. However, since CYP3A4 represents a minor pathway no clinically relevant effect on mianserin exposure is expected. Erlotinib does not inhibit or induce CYP2D6 or CYP1A2.

Description:

See summary

Potential Interaction

Erlotinib

Miconazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Miconazole is extensively metabolized by the liver. Miconazole is also an inhibitor of CYP2C9 (moderate) and CYP3A4 (strong). Erlotinib is metabolised by CYP3A4 (~70%) and concentrations may increase due to inhibition by miconazole. After coadministration with ketoconazole, a strong CYP3A4 inhibitor, erlotinib exposure increased by 86%. A similar effect may occur after coadministration with miconazole. Erlotinib is dosed at/near the maximum tolerated dose (MTD) and thus, any increase in erlotinib exposure may lead to toxicity. Coadministration should be approached with caution. If coadministration is unavoidable, reduce erlotinib dose by 50mg decrements. Monitor closely for erlotinib toxicity and, if available, erlotinib plasma concentrations. Note: after dermal application miconazole is only minimally absorbed. Therefore, no clinical relevant interaction is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Midazolam (oral)

Quality of Evidence: Low

Summary:

Coadministration has been studied and a clinically significant interaction is unlikely. Midazolam is metabolised by CYP3A4 and concentrations will alter due to moderate inhibition by erlotinib. After coadministration with midazolam, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on midazolam exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Midazolam (parenteral)

Quality of Evidence: Low

Summary:

Coadministration has been studied and a clinically significant interaction is unlikely. Midazolam is metabolised by CYP3A4 and concentrations may increase due to moderate inhibition by erlotinib. After coadministration with midazolam, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on midazolam exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Milnacipran

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Milnacipran is mainly eliminated unchanged (50%), and as glucuronides (30%) and oxidative metabolites (20%). Erlotinib is unlikely to interfere with this elimination pathway.

Description:

See summary

No Interaction Expected

Erlotinib

Mirtazapine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Mirtazapine is metabolised to 8-hydroxymirtazapine by CYP2D6 and CYP1A2, and to N-desmethylmirtazapine mainly by CYP3A4. Concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on mirtazapine exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Mometasone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Mometasone is metabolised by CYP3A4 and concentrations may increase due to moderate inhibition by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on mometasone exposure is expected. Note: No relevant interaction are expected with the topical use of mometasone.

Description:

See summary

No Interaction Expected

Erlotinib

Montelukast

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Montelukast is mainly metabolised by CYP2C8 and to a lesser extent by CYPs 3A4 and 2C9. Concentrations may increase due to moderate inhibition of CYP3A4 and CYP2C8 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Moreover, inhibition of CYP2C8 by erlotinib is only established in vitro. No clinically relevant effect on montelukast exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Morphine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Morphine is mainly glucuronidated to morphine-3-glucuronide (UGT2B7>UGT1A1) and, to a lesser extent, to the pharmacologically active morphine-6-glucuronide (UGT2B7>UGT1A1). Concentrations may increase due to inhibition of UGT1A1 by erlotinib, but this effect is only established in vitro. Therefore, no clinically relevant effect on morphine exposure is expected. Additionally, morphine is a substrate of P-gp. Erlotinib does not inhibit or induce P-gp.

Description:

See summary

No Interaction Expected

Erlotinib

Moxifloxacin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Moxifloxacin is predominantly glucuronidated by UGT1A1 and concentrations may increase due to inhibition of by erlotinib, but this effect is only established in vitro. Therefore, no clinically relevant effect on moxifloxacin exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Mycophenolate

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Mycophenolate is mainly glucuronidated by UGT1A9 and UGT2B7. The active metabolite of mycophenolate, mycophenolic acid, is an inhibitor of OAT1/OAT3. Erlotinib does not interact with this metabolic pathway.

Description:

See summary

No Interaction Expected

Erlotinib

Nadroparin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nadroparin is excreted renally by a nonsaturable mechanism. Erlotinib is unlikely to interfere with this elimination pathway.

Description:

See summary

No Interaction Expected

Erlotinib

Nandrolone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nandrolone is metabolised in the liver by alpha-reductase. Erlotinib does not interact with this metabolic pathway.

Description:

See summary

No Interaction Expected

Erlotinib

Naproxen

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Naproxen is mainly glucuronidated by UGT2B7 (major) and demethylated to desmethylnaproxen by CYP2C9 (major) and CYP1A2. Erlotinib does not inhibit or induce UGT2B7, CYP2C9 or CYP1A2.

Description:

See summary

No Interaction Expected

Erlotinib

Nateglinide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nateglinide is mainly metabolised by CYP2C9 (70%) and to a lesser extent by CYP3A4 (30%). Concentrations of nateglinide may alter due to moderate inhibition of CYP3A4 by erlotinib. However, since CYP3A4 represents a minor pathway no clinically relevant effect on nateglinide exposure is expected. Erlotinib does not inhibit or induce CYP2C9.

Description:

See summary

No Interaction Expected

Erlotinib

Nebivolol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nebivolol metabolism involves CYP2D6. Erlotinib does not inhibit or induce CYP2D6.

Description:

See summary

Potential Interaction

Erlotinib

Nefazodone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Nefazodone is metabolised mainly by CYP3A4 and is also a strong inhibitor of CYP3A4. Nefazodone concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on nefazodone exposure is expected. Moreover, erlotinib is metabolised by CYP3A4 (~70%) and concentrations may increase due to inhibition by nefazodone. After coadministration with ketoconazole, a strong CYP3A4 inhibitor, erlotinib exposure increased by 86%. A similar effect may occur after coadministration with nefazodone. Erlotinib is dosed at/near the maximum tolerated dose (MTD) and thus, any increase in erlotinib exposure may lead to toxicity. Coadministration should be approached with caution. If coadministration is unavoidable, reduce erlotinib dose by 50mg decrements. Monitor closely for erlotinib toxicity and, if available, erlotinib plasma concentrations.

Description:

See summary

Potential Interaction

Erlotinib

Nicardipine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Nicardipine is metabolised mainly by CYP3A4 and to a lesser extent by CYP2D6 and CYP2C8. Concentrations may increase due to moderate inhibition of CYP3A4 and CYP2C8 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on nicardipine exposure is expected. Moreover, nicardipine is a weak inhibitor of CYP3A4. Erlotinib is metabolised by CYP3A4 (~70%) and concentrations may increase due to inhibition by nicardipine. After coadministration with ketoconazole, a strong CYP3A4 inhibitor, erlotinib exposure increased by 86%. A similar effect may occur after coadministration with nicardipine. Erlotinib is dosed at/near the maximum tolerated dose (MTD) and thus, any increase in erlotinib exposure may lead to toxicity. Coadministration should be approached with caution. If coadministration is unavoidable, reduce erlotinib dose by 50mg decrements. Monitor closely for erlotinib toxicity and, if available, erlotinib plasma concentrations.

Description:

See summary

No Interaction Expected

Erlotinib

Nicotinamide (Niacinamide)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nicotinamide is converted to N-methylnicotinamide by nicotinamide methyltransferase which in turn is metabolised by xanthine oxidase and aldehyde oxidase. Erlotinib does not interact with this metabolic pathway.

Description:

See summary

No Interaction Expected

Erlotinib

Nifedipine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nifedipine is metabolised mainly by CYP3A4 and concentrations may increase due to moderate inhibition by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on nifedipine exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Nimesulide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nimesulide is extensively metabolised in the liver following multiple pathways including CYP2C9. Erlotinib does not inhibit or induce CYP2C9.

Description:

See summary

No Interaction Expected

Erlotinib

Nisoldipine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nisoldipine is metabolised by CYP3A4 and concentrations may increase due to moderate inhibition by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on nisoldipine exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Nitrendipine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nitrendipine is extensively metabolised mainly by CYP3A4 and concentrations may increase due to moderate inhibition by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on nitrendipine exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Nitrofurantoin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nitrofurantoin is partly metabolised in the liver via glucuronidation and N-acetylation and partly eliminated in the urine as unchanged drug (30-40%). Erlotinib is unlikely to interfere with this metabolic or elimination pathway.

Description:

See summary

No Interaction Expected

Erlotinib

Norelgestromin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Norelgestromin is metabolised to norgestrel (possibly by CYP3A4). Concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on norelgestromin exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Norethisterone (Norethindrone)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Norethindrone is extensively biotransformed, first by reduction and then by sulphate and glucuronide conjugation. Erlotinib is unlikely to interact with this metabolic pathway.

Description:

See summary

No Interaction Expected

Erlotinib

Norgestimate

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Norgestimate is rapidly deacetylated to the active metabolite which is further metabolised via CYP450. Concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on norgestimate exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Norgestrel

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Norgestrel is a racemic mixture with levonorgestrel being biologically active. Levonorgestrel is mainly metabolized by CYP3A4 and is glucuronidated to a minor extent. Concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on norgestrel exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Nortriptyline

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nortriptyline is metabolised mainly by CYP2D6. Erlotinib does not inhibit or induce CYP2D6.

Description:

See summary

No Interaction Expected

Erlotinib

Nystatin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Systemic absorption of nystatin from oral or topical dosage forms is not significant, therefore no drug interactions are expected.

Description:

See summary

No Interaction Expected

Erlotinib

Ofloxacin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ofloxacin is renally eliminated unchanged by glomerular filtration and active tubular secretion via both cationic and anionic transport systems. Erlotinib is unlikely to interfere with this elimination pathway.

Description:

See summary

No Interaction Expected

Erlotinib

Olanzapine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Olanzapine is metabolised mainly by CYP1A2 (major) and CYP2D6, but also by glucuronidation (UGT1A4). Erlotinib does not inhibit or induce CYP1A2, CYP2D6 or UGT1A4.

Description:

See summary

No Interaction Expected

Erlotinib

Olmesartan

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Olmesartan medoxomil is de-esterified to the active metabolite olmesartan which is eliminated in the faeces and urine. Erlotinib is unlikely to interfere with this elimination pathway.

Description:

See summary

Potential Weak Interaction

Erlotinib

Omeprazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Omeprazole is mainly metabolised by CYP2C19 and to a lesser extent by CYP3A4. Concentrations of omeprazole may alter due to moderate inhibition of CYP3A4 by erlotinib. However, since CYP3A4 represents a minor pathway no clinically relevant effect on omeprazole exposure is expected. Erlotinib does not inhibit or induce CYP2C19. Omeprazole is also an inducer of CYP1A2 and an inhibitor of CYP2C19. Erlotinib is not metabolised by CYP1A2 or CYP2C19. Moreover, the bioavailability of erlotinib is pH-dependent and, thus, an increase in gastric pH by omeprazole reduces its bioavailability. Results on whether this decrease in exposure will lead to a decreased efficacy of erlotinib are conflicting. If coadministration is clinically necessary, erlotinib should be administered at the moment at which acid secretion is less inhibited, and that is just before a new dose of omeprazole. Furthermore, erlotinib may be administered concomitantly with an acidic beverage like cola, to overcome decreased bioavailability.

Description:

See summary

No Interaction Expected

Erlotinib

Ondansetron

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ondansetron is metabolised mainly by CYP1A2 and CYP3A4 and to a lesser extent by CYP2D6. Concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on ondansetron exposure is expected. Additionally, ondansetron is a substrate of P-gp. Erlotinib does not inhibit or induce P-gp.

Description:

See summary

No Interaction Expected

Erlotinib

Oxazepam

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Oxazepam is mainly glucuronidated. Concentrations may increase due to inhibition of UGT1A1 by erlotinib, but this effect is only established in vitro. Therefore, no clinically relevant effect on oxazepam exposure is expected.

Description:

See summary

Do Not Coadminister

Erlotinib

Oxcarbazepine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is contraindicated. Oxcarbazepine is extensively metabolized to the active metabolite monohydroxyderivate (MHD) through cytosolic enzymes. Erlotinib does not interact with this metabolic pathway. Both oxcarbazepine and MHD are inducers of CYP3A4 (moderate) and CYP3A5 and are inhibitors of CYP2C19. Erlotinib is metabolised by CYP3A4 (~70%) and concentrations may decrease due to induction by oxcarbazepine. After coadministration with rifampicin, a strong CYP3A4 inducer, erlotinib exposure decreased by 69%. A similar effect may occur after coadministration with oxcarbazepine, although the magnitude and relevancy of the effect are unknown. Avoid concomitant use. If coadministration is unavoidable, increase erlotinib dosage by 50mg at 2-week intervals to a maximum of 450mg as tolerated. Monitor erlotinib plasma concentrations, if available.

Description:

See summary

No Interaction Expected

Erlotinib

Oxprenolol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Oxprenolol is largely metabolised via glucuronidation. Concentrations may increase due to inhibition of UGT1A1 by erlotinib, but this effect is only established in vitro. Therefore, no clinically relevant effect on oxprenolol exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Oxycodone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Oxycodone is metabolised principally to noroxycodone via CYP3A and oxymorphone via CYP2D6. Concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on oxycodone exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Paliperidone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Paliperidone is primarily eliminated renally (possibly via OCT) with minimal metabolism occurring via CYP2D6 and CYP3A4. Concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on paliperidone exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Palonosetron

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Palonosetron is metabolised mainly by CYP3A4 and to a lesser extent by CYP2D6 and CYP1A2. Concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on palonsetron exposure is expected. Additionally, palonosetron is a substrate of P-gp. Erlotinib does not inhibit or induce P-gp.

Description:

See summary

No Interaction Expected

Erlotinib

Pamidronic acid

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pamidronic acid is not metabolised and is cleared from the plasma by uptake into bone and elimination via renal excretion. Erlotinib is unlikely to interfere with this elimination pathway.

Description:

See summary

Potential Weak Interaction

Erlotinib

Pantoprazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Pantoprazole is mainly metabolised by CYP2C19 and to a lesser extent by CYPs 3A4, 2D6 and 2C9. Concentrations of pantoprazole may alter due to moderate inhibition of CYP3A4 by erlotinib. However, since CYP3A4 represents a minor pathway no clinically relevant effect on pantoprazole exposure is expected. Erlotinib does not inhibit or induce CYPs 2C19, 2D6 or 2C9. Moreover, the bioavailability of erlotinib is pH-dependent and, thus, an increase in gastric pH by pantoprazole reduces its bioavailability. Results on whether this decrease in exposure will lead to a decreased efficacy of erlotinib are conflicting. If coadministration is clinically necessary, erlotinib should be administered at the moment at which acid secretion is less inhibited, and that is just before a new dose of pantoprazole. Furthermore, erlotinib may be administered concomitantly with an acidic beverage like cola, to overcome decreased bioavailability.

Description:

See summary

No Interaction Expected

Erlotinib

Para-aminosalicylic acid

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Para-aminosalicylic acid and its acetylated metabolite are mainly excreted in the urine by glomerular filtration and tubular secretion. Erlotinib is unlikely to interfere with this elimination pathway.

Description:

See summary

No Interaction Expected

Erlotinib

Paracetamol (Acetaminophen)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Paracetamol is mainly metabolised by glucuronidation (via UGTs 1A9 (major), 1A6, 1A1, and 2B15) and sulfation and, to a lesser extent, by oxidation (CYPs 2E1 (major), 1A2, 3A4 and 2D6). Acetaminophen concentrations may increase due to inhibition of UGT1A1 by erlotinib, but this effect is only established in vitro. Therefore, no clinically relevant effect on acetaminophen exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Paroxetine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Paroxetine is mainly metabolised by CYP2D6. Paroxetine is also an inhibitor of CYP2D6 (strong) and CYP2C9. Erlotinib does not interact with this metabolic pathway.

Description:

See summary

No Interaction Expected

Erlotinib

Peginterferon alfa-2a

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely.

Description:

See summary

No Interaction Expected

Erlotinib

Penicillins

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Penicillins are mainly eliminated in the urine (20% by glomerular filtration and 80% by tubular secretion via OAT). Erlotinib is unlikely to interfere with this elimination pathway and does not inhibit or induce OATs.

Description:

See summary

No Interaction Expected

Erlotinib

Perazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Perazine is mainly metabolised by CYPs 1A2, 3A4 and 2C19, and to a lesser extent by CYPs 2C9, 2D6 and 2E1, with oxidation via FMO3. Concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on perazine exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Periciazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. The metabolism of periciazine has not been well characterized but is likely to involve CYP2D6. Erlotinib does not inhibit or induce CYP2D6.

Description:

See summary

No Interaction Expected

Erlotinib

Perindopril

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Perindopril is hydrolysed to the active metabolite perindoprilat and is metabolised to other inactive metabolites. Elimination occurs predominantly via the urine. Erlotinib is unlikely to interfere with this elimination or metabolic pathway.

Description:

See summary

No Interaction Expected

Erlotinib

Perphenazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Perphenazine is metabolised by CYP2D6. Erlotinib does not inhibit or induce CYP2D6.

Description:

See summary

No Interaction Expected

Erlotinib

Pethidine (Meperidine)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pethidine is metabolised mainly by CYP2B6 and to a lesser extent by CYP3A4. Concentrations of pethidine may alter due to moderate inhibition of CYP3A4 by erlotinib. However, since CYP3A4 represents a minor pathway no clinically relevant effect on pethidine exposure is expected. Erlotinib does not inhibit or induce CYP2B6.

Description:

See summary

No Interaction Expected

Erlotinib

Phenelzine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Phenelzine is primarily metabolised by oxidation via monoamine oxidase and to a lesser extent acetylation. Erlotinib does not interact with this metabolic pathway.

Description:

See summary

Do Not Coadminister

Erlotinib

Phenobarbital (Phenobarbitone)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is contraindicated. Phenobarbital is metabolized by CYP2C19 and CYP2C9 (major pathway) and to a lesser extent by CYP2E1. Erlotinib does not inhibit or induce CYPs 2C19, 2C9 or 2E1. Phenobarbital is also a strong inducer of CYP3A4, CYP2C9, CYP2C8 and UGTs. Erlotinib is metabolised by CYP3A4 (~70%) and concentrations may decrease due to induction by phenobarbital. After coadministration with rifampicin, a strong CYP3A4 inducer, erlotinib exposure decreased by 69%. A similar effect may occur after coadministration with phenobarbital, although the magnitude and relevancy of the effect are unknown. Avoid concomitant use. If coadministration is unavoidable, increase erlotinib dosage by 50mg at 2-week intervals to a maximum of 450mg as tolerated. Monitor erlotinib plasma concentrations, if available.

Description:

See summary

Potential Interaction

Erlotinib

Phenprocoumon

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Phenprocoumon is mainly metabolised by CYP2C9 and CYP3A4. Concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on phenprocoumon exposure is expected. However, interaction of erlotinib with coumarin-derived anticoagulants leads to an increased International Normalized Ratio (INR) and increased bleeding adverse events. If coadministration is unavoidable, monitor closely for INR or prothrombin time changes.

Description:

See summary

Do Not Coadminister

Erlotinib

Phenytoin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is contraindicated. Phenytoin is mainly metabolized by CYP2C9 and to a lesser extent by CYP2C19. Erlotinib does not inhibit or induce CYP2C9 or CYP2C19. Phenytoin is a strong inducer of CYP3A4, UGT and P-gp. Erlotinib is metabolised by CYP3A4 (~70%) and concentrations may decrease due to induction by phenytoin. After coadministration with rifampicin, a strong CYP3A4 inducer, erlotinib exposure decreased by 69%. A similar effect may occur after coadministration with phenytoin, although the magnitude and relevancy of the effect are unknown. Avoid concomitant use. If coadministration is unavoidable, increase erlotinib dosage by 50mg at 2-week intervals to a maximum of 450mg as tolerated. Monitor erlotinib plasma concentrations, if available.

Description:

See summary

No Interaction Expected

Erlotinib

Phytomenadione (Vitamin K)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. An in vitro study found that the only CYP450 enzyme involved in phytomenadione metabolism was CYP4F2. Erlotinib does not inhibit or induce CYP4F2.

Description:

See summary

No Interaction Expected

Erlotinib

Pimozide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pimozide is mainly metabolised by CYP3A4 and CYP2D6 and to a lesser extent by CYP1A2. Concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on pimozide exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Pindolol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pindolol is partly metabolised to hydroxymetabolites (possibly via CYP2D6) and partly eliminated unchanged in the urine. Erlotinib is unlikely to interfere with this metabolic or elimination pathway.

Description:

See summary

No Interaction Expected

Erlotinib

Pioglitazone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pioglitazone is metabolised mainly by CYP2C8 and to a lesser extent by CYPs 3A4, 1A2 and 2C9. Concentrations may increase due to moderate inhibition of CYP3A4 and CYP2C8 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Moreover, inhibition of CYP2C8 by erlotinib is only established in vitro. No clinically relevant effect on pioglitazone exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Pipotiazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. The metabolism of pipotiazine has not been well described but may involve CYP2D6. Erlotinib does not inhibit or induce CYP2D6.

Description:

See summary

No Interaction Expected

Erlotinib

Piroxicam

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Piroxicam is primarily metabolised by CYP2C9. Erlotinib does not inhibit or induce CYP2C9.

Description:

See summary

No Interaction Expected

Erlotinib

Pitavastatin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pitavastatin is metabolised by UGTs 1A3 and 2B7 with minimal metabolism by CYPs 2C9 and 2C8. Concentrations may increase due to moderate inhibition of CYP2C8 by erlotinib, but this effect is only established in vitro. Coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on pitavastatin exposure is expected. Pitavastatin is also a substrate of OATP1B1. Erlotinib does not inhibit or induce OATP1B1.

Description:

See summary

Potential Interaction

Erlotinib

Posaconazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Posaconazole is primarily metabolised by UGTs and is a substrate of P-gp. Moreover, posaconazole is a strong inhibitor of CYP3A4. Erlotinib is metabolised by CYP3A4 (~70%) and concentrations may increase due to inhibition by posaconazole. After coadministration with ketoconazole, a strong CYP3A4 inhibitor, erlotinib exposure increased by 86%. A similar effect may occur after coadministration with posaconazole. Erlotinib is dosed at/near the maximum tolerated dose (MTD) and thus, any increase in erlotinib exposure may lead to toxicity. Coadministration should be approached with caution. If coadministration is unavoidable, reduce erlotinib dose by 50mg decrements. Monitor closely for erlotinib toxicity and, if available, erlotinib plasma concentrations.

Description:

See summary

No Interaction Expected

Erlotinib

Potassium

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on limited data available an interaction appears unlikely. Potassium is eliminated renally. Erlotinib is unlikely to interfere with this elimination pathway.

Description:

See summary

No Interaction Expected

Erlotinib

Prasugrel

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Prasugrel is a prodrug and is converted to its active metabolite mainly by CYP3A4 and CYP2B6 and to a lesser extent by CYP2C9 and CYP2C19. Concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on prasugrel exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Pravastatin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pravastatin is minimally metabolised via CYP enzymes and is substrate of OATP1B1. Erlotinib does not inhibit or induce OATP1B1.

Description:

See summary

No Interaction Expected

Erlotinib

Prazosin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Prazosin is extensively metabolised, primarily by demethylation and conjugation. Erlotinib does not interact with this metabolic pathway.

Description:

See summary

No Interaction Expected

Erlotinib

Prednisolone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Prednisolone undergoes hepatic metabolism via CYP3A4 and concentrations may increase due to moderate inhibition by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on prednisolone exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Prednisone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Prednisone is converted to the active metabolite prednisolone by 11-B-hydroxydehydrogenase. Erlotinib does not interact with this metabolic pathway. Prednisolone is then metabolised by CYP3A4 and concentrations may increase due to moderate inhibition by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on prednisone exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Pregabalin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pregabalin is cleared mainly by glomerular filtration (90% as unchanged drug). Erlotinib is unlikely to interfere with this elimination pathway.

Description:

See summary

No Interaction Expected

Erlotinib

Prochlorperazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Prochlorperazine is metabolised by CYP2D6 and CYP2C19. Erlotinib does not inhibit or induce CYP2D6 or CYP2C19.

Description:

See summary

No Interaction Expected

Erlotinib

Promethazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Promethazine is metabolised by CYP2D6. Erlotinib does not inhibit or induce CYP2D6.

Description:

See summary

No Interaction Expected

Erlotinib

Propafenone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Propafenone is metabolised mainly by CYP2D6 and to a lesser extent by CYP1A2 and CYP3A4. Concentrations of propafenone may alter due to moderate inhibition of CYP3A4 by erlotinib. However, since CYP3A4 represents a minor pathway no clinically relevant effect on propafenone exposure is expected. Erlotinib does not inhibit or induce CYP2D6 or CYP1A2.

Description:

See summary

No Interaction Expected

Erlotinib

Propranolol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Propranolol is metabolised by 3 routes (aromatic hydroxylation by CYP2D6, N-dealkylation followed by side chain hydroxylation via CYPs 1A2, 2C19, 2D6, and direct glucuronidation). Erlotinib is unlikely to interact with this metabolic pathway.

Description:

See summary

No Interaction Expected

Erlotinib

Prucalopride

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Prucalopride is minimally metabolised and mainly eliminated renally, partly by active secretion by renal transporters. Prucalopride is also a substrate of P-gp. Erlotinib is unlikely to interact with this metabolic or elimination pathway.

Description:

See summary

No Interaction Expected

Erlotinib

Pyrazinamide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pyrazinamide is mainly metabolised by xanthine oxidase. Erlotinib does not interact with this metabolic pathway.

Description:

See summary

No Interaction Expected

Erlotinib

Pyridoxine (Vitamin B6)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely.

Description:

See summary

No Interaction Expected

Erlotinib

Quetiapine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Quetiapine is primarily metabolised by CYP3A4 and concentrations may increase due to moderate inhibition of by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on quetiapine exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Quinapril

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Quinapril is de-esterified to the active metabolite quinaprilat which is eliminated primarily by renal excretion via OAT3. Erlotinib is unlikely to interfere with this elimination pathway and does not inhibit or induce OATs.

Description:

See summary

Potential Interaction

Erlotinib

Quinidine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Quinidine is mainly metabolised by CYP3A4 and to a lesser extent by CYP2C9 and CYP2E1. Concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on quinidine exposure is expected. Quinidine is a substrate of P-gp. Erlotinib does not inhibit or induce P-gp. Quinidine is also an inhibitor of CYP2D6 (strong), CYP3A4 (weak) and P-gp (moderate). Erlotinib is metabolised by CYP3A4 (~70%) and concentrations may increase due to inhibition by quinidine. After coadministration with ketoconazole, a strong CYP3A4 inhibitor, erlotinib exposure increased by 86%. A similar effect may occur after coadministration with quinidine. Erlotinib is dosed at/near the maximum tolerated dose (MTD) and thus, any increase in erlotinib exposure may lead to toxicity. Co-administration should be approached with caution. If coadministration is unavoidable, reduce erlotinib dose by 50mg decrements. Monitor closely for erlotinib toxicity and, if available, erlotinib plasma concentrations.

Description:

See summary

Potential Weak Interaction

Erlotinib

Rabeprazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Rabeprazole is mainly metabolised via non-enzymatic reduction and to a lesser extent by CYP2C19 and CYP3A4. Concentrations of rabeprazole may alter due to moderate inhibition of CYP3A4 by erlotinib. However, since CYP3A4 represents a minor pathway no clinically relevant effect on rabeprazole exposure is expected. Erlotinib does not inhibit or induce CYP2C19. Moreover, the bioavailability of erlotinib is pH-dependent and, thus, an increase in gastric pH by rabeprazole reduces its bioavailability. Results on whether this decrease in exposure will lead to a decreased efficacy of erlotinib are conflicting. If coadministration is clinically necessary, erlotinib should be administered at the moment at which acid secretion is less inhibited, and that is just before a new dose of rabeprazole. Furthermore, erlotinib may be administered concomitantly with an acidic beverage like cola, to overcome decreased bioavailability.

Description:

See summary

No Interaction Expected

Erlotinib

Ramipril

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ramipril is hydrolysed to the active metabolite ramiprilat, and is metabolised to the diketopiperazine ester, diketopiperazine acid and the glucuronides of ramipril and ramiprilat. Erlotinib does not interact with this metabolic pathway.

Description:

See summary

Potential Weak Interaction

Erlotinib

Ranitidine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ranitidine is excreted via OAT1/OAT3. Erlotinib does not inhibit or induce OATs. However, the bioavailability of erlotinib is pH-dependent and, thus, an increase in gastric pH by ranitidine reduces its bioavailability. Results on whether this decrease in exposure will lead to a decreased efficacy of erlotinib are conflicting. If coadministration is clinically necessary, erlotinib should be administered at the moment at which acid secretion is less inhibited, and that is just before a new dose of ranitidine. Furthermore, erlotinib may be administered concomitantly with an acidic beverage like cola, to overcome decreased bioavailability.

Description:

See summary

Potential Interaction

Erlotinib

Ranolazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Ranolazine is primarily metabolized by CYP3A4 and to a lesser extent by CYP2D6. Concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on ranolazine exposure is expected. Ranolazine is also a substrate of P-gp. Erlotinib does not inhibit or induce P-gp. Moreover, ranolazine is a weak inhibitor of P-gp, CYP3A4 and CYP2D6. Erlotinib is metabolised by CYP3A4 (~70%) and concentrations may increase due to inhibition by ranolazine. After coadministration with ketoconazole, a strong CYP3A4 inhibitor, erlotinib exposure increased by 86%. A similar effect may occur after coadministration with ranolazine. Erlotinib is dosed at/near the maximum tolerated dose (MTD) and thus, any increase in erlotinib exposure may lead to toxicity. Coadministration should be approached with caution. If coadministration is unavoidable, reduce erlotinib dose by 50mg decrements. Monitor closely for erlotinib toxicity and, if available, erlotinib plasma concentrations.

Description:

See summary

No Interaction Expected

Erlotinib

Reboxetine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Reboxetine is metabolised by CYP3A4 and concentrations may increase due to moderate inhibition by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on reboxetine exposure is expected. Additionally, in vitro data indicate reboxetine to be a weak inhibitor of CYP3A4 but in vivo data showed no inhibitory effect on CYP3A4.

Description:

See summary

No Interaction Expected

Erlotinib

Repaglinide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Repaglinide is metabolised by CYP2C8 and CYP3A4, with clinical data indicating it is a substrate of the hepatic transporter OATP1B1. Concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Moreover, inhibition of CYP2C8 by erlotinib is only established in vitro. No clinically relevant effect on repaglinide exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Retinol (Vitamin A)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Vitamin A esters are hydrolysed by pancreatic enzymes to retinol, which is then absorbed and re-esterified. Some retinol is stored in the liver but retinol not stored in the liver undergoes glucuronide conjugation and subsequent oxidation to retinal and retinoic acid. Erlotinib does not interact with this metabolic pathway.

Description:

See summary

No Interaction Expected

Erlotinib

Riboflavin (Vitamin B2)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely.

Description:

See summary

Do Not Coadminister

Erlotinib

Rifabutin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is contraindicated. Rifabutin is metabolised by CYP3A4 and via deacetylation. Concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on rifabutin exposure is expected. Rifabutin is also a strong CYP3A4 and P-gp inducer. Erlotinib is metabolised by CYP3A4 (~70%) and concentrations may decrease due to induction by rifabutin. After coadministration with rifampicin, a strong CYP3A4 inducer, erlotinib exposure decreased by 69%. A similar effect may occur after coadministration with rifabutin, although the magnitude and relevancy of the effect are unknown. Avoid concomitant use. If coadministration is unavoidable, increase erlotinib dosage by 50mg at 2-week intervals to a maximum of 450mg as tolerated. Monitor erlotinib plasma concentrations, if available.

Description:

See summary

Do Not Coadminister

Erlotinib

Rifampicin

Quality of Evidence: Low

Summary:

Coadministration has been studied and is contraindicated. Rifampicin is metabolised via deacetylation and is also a strong CYP3A4 and P-gp inducer. Erlotinib is metabolised by CYP3A4 (~70%) and concentrations will decrease due to induction by rifampicin. After coadministration with rifampicin, erlotinib exposure decreased by 69%. Avoid concomitant use. If coadministration is unavoidable, increase erlotinib dosage by 50mg at 2-week intervals to a maximum of 450mg as tolerated. Monitor erlotinib plasma concentrations, if available.

Description:

See summary

Do Not Coadminister

Erlotinib

Rifapentine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is contraindicated. Rifapentine is metabolised via deacetylation and is also a strong CYP3A4, CYP2C8 and P-gp inducer. Erlotinib is metabolised by CYP3A4 (~70%) and concentrations may decrease due to induction by rifapentine. After coadministration with rifampicin, a strong CYP3A4 inducer, erlotinib exposure decreased by 69%. A similar effect may occur after coadministration with rifapentine, although the magnitude and relevancy of the effect are unknown. Avoid concomitant use. If coadministration is unavoidable, increase erlotinib dosage by 50mg at 2-week intervals to a maximum of 450mg as tolerated. Monitor erlotinib plasma concentrations, if available.

Description:

See summary

No Interaction Expected

Erlotinib

Rifaximin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Rifaximin is mainly excreted in faeces, almost entirely as unchanged drug. Erlotinib is unlikely to interfere with this elimination pathway.

Description:

See summary

No Interaction Expected

Erlotinib

Risperidone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Risperidone is metabolised by CYP2D6 and to a lesser extent by CYP3A4. Risperidone is also a substrate of P-gp. Concentrations of risperidone may alter due to moderate inhibition of CYP3A4 by erlotinib. However, since CYP3A4 represents a minor pathway no clinically relevant effect on risperidone exposure is expected. Erlotinib does not inhibit or induce CYP2D6 or P-gp.

Description:

See summary

No Interaction Expected

Erlotinib

Rivaroxaban

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Rivaroxaban is partly metabolised in the liver (by CYP3A4, CYP2J2 and hydrolytic enzymes) and partly eliminated unchanged in urine. Concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on rivaroxaban exposure is expected. Rivaroxaban is also a substrate of P-gp and BCRP. Erlotinib does not inhibit or induce P-gp or BCRP.

Description:

See summary

No Interaction Expected

Erlotinib

Rosiglitazone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Rosiglitazone is metabolised mainly by CYP2C8 and to a lesser extent by CYP2C9. Concentrations may increase due to moderate inhibition of CYP2C8 by erlotinib, but this effect is only established in vitro. After coadministration with paclitaxel, a CYP3A4/2C8 substrate, erlotinib did not change paclitaxel exposure. Therefore, no clinically relevant effect on rosiglitazone exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Rosuvastatin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Rosuvastatin is largely excreted unchanged via the faeces via OATP1B1 and is substrate of BCRP. Erlotinib does not inhibit or induce OATP1B1 or BCRP.

Description:

See summary

No Interaction Expected

Erlotinib

Salbutamol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Salbutamol is metabolised to the inactive salbutamol-4’-O-sulphate. Erlotinib does not interact with this metabolic pathway.

Description:

See summary

No Interaction Expected

Erlotinib

Salmeterol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Salmeterol is metabolised by CYP3A4. The systemic exposure of salmeterol is low. Concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on salmeterol exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Saxagliptin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Saxagliptin is mainly metabolised by CYP3A4 and is a substrate of P-gp. Concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on saxagliptin exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Senna

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Senna glycosides are hydrolysed by colonic bacteria in the intestinal tract and the active anthraquinones liberated into the colon. Excretion occurs in the urine and the faeces and also in other secretions. No clinically significant interactions are known.

Description:

See summary

No Interaction Expected

Erlotinib

Sertindole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Sertindole is metabolised by CYP2D6 and CYP3A4. Concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on sertindole exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Sertraline

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Sertraline is mainly metabolised by CYP2B6 and to a lesser extent by CYPs 2C9, 2C19, 2D6 and 3A4. Concentrations of sertraline may alter due to moderate inhibition of CYP3A4 by erlotinib. However, since CYP3A4 represents a minor pathway no clinically relevant effect on sertraline exposure is expected. Erlotinib does not inhibit or induce CYPs 2B6, 2C9, 2C19 or 2D6.

Description:

See summary

No Interaction Expected

Erlotinib

Sildenafil (Pulmonary Arterial Hypertension)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Sildenafil is metabolised mainly by CYP3A4 and to a lesser extent by CYP2C9. Concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on sildenafil exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Simvastatin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Simvastatin is metabolised by CYP3A4 and concentrations may increase due to moderate inhibition by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on simvastatin exposure is expected. Simvastatin is also a substrate of BCRP and the active metabolite is a substrate of OATP1B1. Erlotinib does not inhibit or induce BCRP or OATP1B1.

Description:

See summary

No Interaction Expected

Erlotinib

Sirolimus

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Sirolimus is metabolised by CYP3A4 and is substrate of P-gp. Concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on sirolimus exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Sitagliptin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Sitagliptin is primarily eliminated in urine as unchanged drug (active secretion by OAT3, OATP4C1, and P-gp) and metabolism by CYP3A4 represents a minor metabolic pathway. Concentrations of sitagliptin may alter due to moderate inhibition of CYP3A4 by erlotinib. However, since CYP3A4 represents a minor pathway no clinically relevant effect on sitagliptin exposure is expected. Erlotinib does not inhibit or induce OATs or P-gp.

Description:

See summary

No Interaction Expected

Erlotinib

Sodium nitroprusside

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Sodium nitroprusside is rapidly metabolised, likely by interaction with sulfhydryl groups in the erythrocytes and tissues. Cyanogen (cyanide radical) is produced which is converted to thiocyanate in the liver by the enzyme thiosulfate sulfurtransferase. Erlotinib does not interact with this metabolic pathway.

Description:

See summary

No Interaction Expected

Erlotinib

Sotalol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Sotalol is excreted unchanged via renal elimination. Erlotinib is unlikely to interfere with this elimination pathway.

Description:

See summary

No Interaction Expected

Erlotinib

Spectinomycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Spectinomycin is predominantly eliminated unchanged in the kidneys via glomerular filtration. Erlotinib is unlikely to interfere with this elimination pathway.

Description:

See summary

No Interaction Expected

Erlotinib

Spironolactone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Spironolactone is partly metabolised by the flavin containing monooxygenases. Erlotinib does not interact with this metabolic pathway.

Description:

See summary

No Interaction Expected

Erlotinib

Stanozolol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Stanozolol undergoes hepatic metabolism. Erlotinib does not interact with this metabolic pathway.

Description:

See summary

Do Not Coadminister

Erlotinib

St John's Wort

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is contraindicated. St John’s wort is a P-gp and CYP3A4 inducer. Erlotinib is metabolised by CYP3A4 (~70%) and concentrations may decrease due to induction by St John’s Wort. After coadministration with rifampicin, a strong CYP3A4 inducer, erlotinib exposure decreased by 69%. A similar effect may occur after coadministration with St John’s Wort, although the magnitude and relevancy of the effect are unknown. Coadministration should be avoided.

Description:

See summary

No Interaction Expected

Erlotinib

Streptokinase

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Like other proteins, streptokinase is metabolised proteolytically in the liver and eliminated via the kidneys. Erlotinib is unlikely to interfere with this metabolic or elimination pathway.

Description:

See summary

No Interaction Expected

Erlotinib

Streptomycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Streptomycin is eliminated by glomerular filtration. Erlotinib is unlikely to interfere with this elimination pathway.

Description:

See summary

No Interaction Expected

Erlotinib

Sulfadiazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. In vitro studies suggest a role of CYP2C9 in sulfadiazine metabolism. Erlotinib does not inhibit or induce CYP2C9.

Description:

See summary

No Interaction Expected

Erlotinib

Sulpiride

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Sulpiride is mainly excreted in the urine and faeces as unchanged drug. Erlotinib is unlikely to interfere with this elimination pathway.

Description:

See summary

Potential Interaction

Erlotinib

Tacrolimus

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Tacrolimus is metabolised mainly by CYP3A4 and concentrations may increase due to moderate inhibition by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on tacrolimus exposure is expected. Tacrolimus is also an inhibitor of CYP3A4 and OATP1B1 in vitro but produced modest inhibition of CYP3A4 and OATP1B1 in the range of clinical concentrations. Erlotinib is metabolised by CYP3A4 (~70%) and concentrations may increase due to inhibition by tacrolimus. After coadministration with ketoconazole, a strong CYP3A4 inhibitor, erlotinib exposure increased by 86%. Erlotinib is dosed at/near the maximum tolerated dose (MTD) and thus, any increase in erlotinib exposure may lead to toxicity. Coadministration should be approached with caution. If coadministration is unavoidable, reduce erlotinib dose by 50mg decrements. Monitor closely for erlotinib toxicity and, if available, erlotinib plasma concentrations.

Description:

See summary

No Interaction Expected

Erlotinib

Tadalafil (Pulmonary Arterial Hypertension)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tadalafil is metabolised by CYP3A4 and concentrations may increase due to moderate inhibition by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on tadalafil exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Tamsulosin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tamsulosin is metabolised mainly by CYP3A4 and to a lesser extent by CYP2D6. Concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on tamsulosin exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Tazobactam

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tazobactam is excreted as unchanged drug (approximately 80%) and inactive metabolite (approximately 20%) in the urine. Erlotinib is unlikely to interfere with this elimination pathway.

Description:

See summary

Potential Interaction

Erlotinib

Telithromycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Telithromycin is metabolised by CYP3A4 (50%) with the remaining 50% metabolised via non-CYP mediated pathways. Concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on telithromycin exposure is expected. Telithromycin is also an inhibitor of CYP3A4 (strong) and P-gp. The clinical relevance of P-gp inhibition is unknown. Erlotinib is metabolised by CYP3A4 (~70%) and concentrations may increase due to inhibition by telithromycin. After coadministration with ketoconazole, a strong CYP3A4 inhibitor, erlotinib exposure increased by 86%. A similar effect may occur after coadministration with telithromycin. Erlotinib is dosed at/near the maximum tolerated dose (MTD) and thus, any increase in erlotinib exposure may lead to toxicity. Coadministration should be approached with caution. If coadministration is unavoidable, reduce erlotinib dose by 50mg decrements. Monitor closely for erlotinib toxicity and, if available, erlotinib plasma concentrations.

Description:

See summary

No Interaction Expected

Erlotinib

Telmisartan

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Telmisartan is mainly glucuronidated by UGT1A3. Erlotinib does not inhibit or induce UGT1A3.

Description:

See summary

No Interaction Expected

Erlotinib

Temazepam

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Temazepam is mainly glucuronidated. Concentrations may increase due to inhibition of UGT1A1 by erlotinib, but this effect is only established in vitro. Therefore, no clinically relevant effect on temazepam exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Terbinafine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Terbinafine is metabolised by CYPs 1A2, 2C9, 3A4 and to a lesser extent CYP2C8 and CYP2C19. Concentrations may increase due to moderate inhibition of CYP3A4 and CYP2C8 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on terbinafine exposure is expected. Terbinafine is also a moderate-strong inhibitor of CYP2D6. Erlotinib is not metabolised by CYP2D6.

Description:

See summary

No Interaction Expected

Erlotinib

Testosterone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Testosterone is metabolised by CYP3A4 and concentrations may increase due to moderate inhibition by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on testosterone exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Tetracycline

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tetracycline is eliminated unchanged primarily by glomerular filtration. Erlotinib is unlikely to interfere with this elimination pathway.

Description:

See summary

No Interaction Expected

Erlotinib

Theophylline

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Theophylline is mainly metabolised by CYP1A2. Erlotinib does not inhibit or induce CYP1A2.

Description:

See summary

No Interaction Expected

Erlotinib

Thiamine (Vitamin B1)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely.

Description:

See summary

No Interaction Expected

Erlotinib

Thioridazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Thioridazine is metabolised by CYP2D6 and to a lesser extent by CYP3A4. Concentrations of thioridazine may alter due to moderate inhibition of CYP3A4 by erlotinib. However, since CYP3A4 represents a minor pathway no clinically relevant effect on thioridazine exposure is expected. Erlotinib does not inhibit or induce CYP2D6.

Description:

See summary

No Interaction Expected

Erlotinib

Tiapride

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tiapride is excreted largely unchanged in urine. Erlotinib is unlikely to interfere with this elimination pathway.

Description:

See summary

Potential Interaction

Erlotinib

Ticagrelor

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Ticagrelor is a substrate of CYP3A4 and P-gp. Concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on ticagrelor exposure is expected. Ticagrelor is also a weak inhibitor of CYP3A4. Erlotinib is metabolised by CYP3A4 (~70%) and concentrations may increase due to inhibition by ticagrelor. After coadministration with ketoconazole, a strong CYP3A4 inhibitor, erlotinib exposure increased by 86%. A similar effect may occur after coadministration with ticagrelor. Erlotinib is dosed at/near the maximum tolerated dose (MTD) and thus, any increase in erlotinib exposure may lead to toxicity. Coadministration should be approached with caution. If coadministration is unavoidable, reduce erlotinib dose by 50mg decrements. Monitor closely for erlotinib toxicity and, if available, erlotinib plasma concentrations.

Description:

See summary

No Interaction Expected

Erlotinib

Timolol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Timolol is predominantly metabolised in the liver by CYP2D6. Erlotinib does not inhibit or induce CYP2D6. Note: the systemic absorption of timolol after ocular administration is low. Therefore, a relevant interaction via CYP2D6 is unlikely.

Description:

See summary

No Interaction Expected

Erlotinib

Tinzaparin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tinzaparin is renally excreted as unchanged or almost unchanged drug. Erlotinib is unlikely to interfere with this elimination pathway.

Description:

See summary

No Interaction Expected

Erlotinib

Tolbutamide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tolbutamide is mainly metabolised by CYP2C9 and to a lesser extent by CYPs 2C8 and 2C19. Concentrations may increase due to moderate inhibition of CYP2C8 by erlotinib, but this effect is only established in vitro. After coadministration with paclitaxel, a CYP3A4/2C8 substrate, erlotinib did not change paclitaxel exposure. Therefore, no clinically relevant effect on tolbutamide exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Tolterodine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tolterodine is primarily metabolised by CYP2D6 with CYP3A4 playing a minor role. Concentrations of tolterodine may alter due to moderate inhibition of CYP3A4 by erlotinib. However, since CYP3A4 represents a minor pathway no clinically relevant effect on tolterodine exposure is expected. Erlotinib does not inhibit or induce CYP2D6.

Description:

See summary

No Interaction Expected

Erlotinib

Torasemide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Torasemide is metabolised mainly by CYP2C9. Furthermore, OAT1/3 are the major transporters of loop and thiazide diuretics. Secretion of these diuretics into the urinary tract by transporters in the proximal tubular cells is necessary for the diuretic effect in later tubule segments. Erlotinib does not inhibit or induce CYP2C9 or OATs.

Description:

See summary

No Interaction Expected

Erlotinib

Tramadol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tramadol is metabolised by CYPs 3A4, 2B6, and 2D6. Concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on tramadol exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Trandolapril

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Trandolapril is hydrolysed to trandolaprilat. Erlotinib does not interact with this metabolic pathway.

Description:

See summary

No Interaction Expected

Erlotinib

Tranexamic acid

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tranexamic acid is mainly cleared by glomerular filtration. Erlotinib is unlikely to interfere with this elimination pathway.

Description:

See summary

No Interaction Expected

Erlotinib

Tranylcypromine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tranylcypromine is hydroxylated and acetylated. Erlotinib does not interact with this metabolic pathway.

Description:

See summary

No Interaction Expected

Erlotinib

Trazodone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Trazodone is primarily metabolised by CYP3A4 and concentrations may increase due to moderate inhibition by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on trazodone exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Triamcinolone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Triamcinolone is metabolised by CYP3A4 and concentrations may increase due to moderate inhibition by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on triamcinolone exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Triazolam

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Triazolam is metabolised by CYP3A4 and concentrations may increase due to moderate inhibition by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on triazolam exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Trimethoprim/Sulfamethoxazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Trimethoprim is primarily eliminated by the kidneys through glomerular filtration and tubular secretion. Erlotinib is unlikely to interfere with this elimination pathway. To a lesser extent (approximately 30%) trimethoprim is metabolised by CYP enzymes (in vitro data suggest CYP3A4, CYP1A2 and CYP2C9). Concentrations may increase due to moderate CYP3A4 inhibition by erlotinib. However, since CYP3A4 represents a minor pathway no clinically relevant effect on trimethoprim exposure is expected. Sulfamethoxazole is metabolised by CYP2C9. Erlotinib does not inhibit or induce CYP2C9. Trimethoprim is also a weak CYP2C8 inhibitor and in vitro data also suggest that trimethoprim is an inhibitor of OCT2 and MATE1. Sulfamethoxazole is a weak inhibitor of CYP2C9. Erlotinib is not metabolised by CYP2C8 or CYP2C9 and is not a substrate of OCT2 or MATE1.

Description:

See summary

No Interaction Expected

Erlotinib

Trimipramine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Trimipramine is metabolised mainly by CYP2D6. Erlotinib does not inhibit or induce CYP2D6.

Description:

See summary

No Interaction Expected

Erlotinib

Tropisetron

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tropisetron is metabolised mainly by CYP2D6. Tropisetron is also a substrate of P-gp. Erlotinib does not inhibit or induce CYP2D6 or P-gp.

Description:

See summary

No Interaction Expected

Erlotinib

Ulipristal

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ulipristal is mainly metabolised by CYP3A4 and to a lesser extent CYP1A2 and CYP2D6. Concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on ulipristal exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Valproic acid (Valproate)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Valproic acid is primarily metabolized by glucuronidation (50%) and mitochondrial beta-oxidation (30-40%). To a lesser extent (10%) valproic acid is metabolized by CYP2C9 and CYP2C19. Valproic acid is also an inhibitor of CYP2C9. Erlotinib does not interact with this metabolic pathway.

Description:

See summary

No Interaction Expected

Erlotinib

Valsartan

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Valsartan is eliminated unchanged mostly through biliary excretion. Erlotinib is unlikely to interfere with this elimination pathway.

Description:

See summary

No Interaction Expected

Erlotinib

Vancomycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Vancomycin is excreted unchanged via glomerular filtration. Erlotinib is unlikely to interfere with this elimination pathway.

Description:

See summary

No Interaction Expected

Erlotinib

Venlafaxine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Venlafaxine is mainly metabolised by CYP2D6 and to a lesser extent by CYPs 3A4, 2C19 and 2C9. Concentrations of venlafaxine may alter due to moderate inhibition of CYP3A4 by erlotinib. However, since CYP3A4 represents a minor pathway no clinically relevant effect on venlafaxine exposure is expected. Erlotinib does not inhibit or induce CYPs 2D6, 2C19 or 2C9.

Description:

See summary

Potential Interaction

Erlotinib

Verapamil

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Verapamil is metabolised mainly by CYP3A4 and to a lesser extent by CYPs 1A2, 2C8 and 2C9. Concentrations may increase due to moderate inhibition of CYP3A4 and CYP2C8 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on verapamil exposure is expected. Verapamil is also an inhibitor of CYP3A4 (moderate) and P-gp (strong). Erlotinib is metabolised by CYP3A4 (~70%) and concentrations may increase due to inhibition by verapamil. After coadministration with ketoconazole, a strong CYP3A4 inhibitor, erlotinib exposure increased by 86%. A similar effect may occur after coadministration with verapamil. Erlotinib is dosed at/near the maximum tolerated dose (MTD) and thus, any increase in erlotinib exposure may lead to toxicity. Coadministration should be approached with caution. If coadministration is unavoidable, reduce erlotinib dose by 50mg decrements. Monitor closely for erlotinib toxicity and, if available, erlotinib plasma concentrations.

Description:

See summary

No Interaction Expected

Erlotinib

Vildagliptin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Vildagliptin is inactivated via non-CYP mediated hydrolysis and is a substrate of P-gp. Erlotinib does not interact with this metabolic pathway.

Description:

See summary

No Interaction Expected

Erlotinib

Vitamin E

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely.

Description:

See summary

Potential Interaction

Erlotinib

Voriconazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Voriconazole is metabolised by CYP2C19 (major pathway) and to a lesser extent by CYP3A4 and CYP2C9. Concentrations of voriconazole may alter due to moderate inhibition of CYP3A4 by erlotinib. However, since CYP3A4 represents a minor pathway no clinically relevant effect on voriconazole exposure is expected. Erlotinib does not inhibit or induce CYP2C19 or CYP2C9. Voriconazole is also a strong inhibitor of CYP3A4 and a weak inhibitor of CYPs 2C9, 2C19 and 2B6. Erlotinib is metabolised by CYP3A4 (~70%) and concentrations may increase due to inhibition by voriconazole. After coadministration with ketoconazole, a strong CYP3A4 inhibitor, erlotinib exposure increased by 86%. A similar effect may occur after coadministration with voriconazole. Erlotinib is dosed at/near the maximum tolerated dose (MTD) and thus, any increase in erlotinib exposure may lead to toxicity. Coadministration should be approached with caution. If coadministration is unavoidable, reduce erlotinib dose by 50mg decrements. Monitor closely for erlotinib toxicity and, if available, erlotinib plasma concentrations.

Description:

See summary

Potential Interaction

Erlotinib

Warfarin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Warfarin is a mixture of enantiomers which are metabolised by different cytochromes. R-warfarin is primarily metabolised by CYP1A2 and CYP3A4. Concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on warfarin exposure is expected. S-warfarin (more potent) is metabolised by CYP2C9. Erlotinib does not inhibit or induce CYP2C9. However, interaction of erlotinib with coumarin-derived anticoagulants leads to an increased International Normalized Ratio (INR) and increased bleeding adverse events. A case report described an increased INR of 9.1 from a previous stable range of 2.1-3.2 in a 47-year-old male non-small-cell lung cancer patient after concomitant treatment of warfarin (2.5 mg daily) and erlotinib (150 mg daily). 1 day after discontinuation of erlotinib the patients INR fell to 2.4. If coadministration is unavoidable, monitor closely for INR or prothrombin time changes.

Description:

See summary

No Interaction Expected

Erlotinib

Xipamide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Approximately 90% of xipamide is excreted in the urine, mainly as unchanged drug (~50%) and glucuronides (30%). OAT1/3 are the major transporters of loop and thiazide diuretics. Secretion of these diuretics into the urinary tract by transporters in the proximal tubular cells is necessary for the diuretic effect in later tubule segments. Erlotinib is unlikely to interfere with this elimination pathway and does not inhibit or induce OATs.

Description:

See summary

No Interaction Expected

Erlotinib

Zaleplon

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Zaleplon is mainly metabolised by aldehyde oxidase and to a lesser extent CYP3A4. Concentrations of zaleplon may alter due to moderate inhibition of CYP3A4 by erlotinib. However, since CYP3A4 represents a minor pathway no clinically relevant effect on zaleplon exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Ziprasidone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Approximately two thirds of ziprasidone metabolic clearance is by reduction, with less than one third by CYP enzymes (mainly CYP3A4). Concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on ziprasidone exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Zoledronic acid

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Zoledronic acid is not metabolised and is cleared from the plasma by uptake into bone and elimination via renal excretion. Erlotinib is unlikely to interfere with this elimination pathway.

Description:

See summary

No Interaction Expected

Erlotinib

Zolpidem

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Zolpidem is metabolised mainly by CYP3A4 and to a lesser extent by CYP2C9, CYP2C19, CYP2D6 and CYP1A2. Concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on zolpidem exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Zopiclone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Zopiclone is metabolised mainly by CYP3A4 and to a lesser extent by CYP2C8. Concentrations may increase due to moderate inhibition of CYP3A4 and CYP2C8 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on zopiclone exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Zotepine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Zotepine is mainly metabolised by CYP3A4 and to a lesser extent by CYP1A2 and CYP2D6. Concentrations may increase due to inhibition of UGT1A1 by erlotinib, but this effect is only established in vitro. No relevant effect on zotepine exposure is expected. Furthermore, concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on zotepine exposure is expected.

Description:

See summary

No Interaction Expected

Erlotinib

Zuclopenthixol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Zuclopenthixol is metabolised by sulphoxidation, N-dealkylation (via CYP2D6 and CYP3A4) and glucuronidation. Concentrations may increase due to moderate inhibition of CYP3A4 by erlotinib. After coadministration with midazolam, a CYP3A4 substrate, erlotinib decreased oral midazolam exposure by up to 24%. However, coadministration with paclitaxel, a CYP3A4/2C8 substrate, did not change paclitaxel exposure. Therefore, no clinically relevant effect on zuclopenthixol exposure is expected.

Description:

See summary