Cancer Drug Interactions from Radboud UMC and University of Liverpool

No Interaction Expected

Gefitinib

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. Gefitinib does not interact with this metabolic pathway.

Description:

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Potential Interaction

Gefitinib

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. Gefitinib does not inhibit or induce CYPs 2C9, 1A2 or 2C19. However, after coadministration of gefitinib with acenocoumarol, increased INR values have been reported. If coadministration is unavoidable, closely monitor INR/PT and signs of bleeding.

Description:

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No Interaction Expected

Gefitinib

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). Gefitinib does not inhibit or induce UGTs.

Description:

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No Interaction Expected

Gefitinib

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%). Gefitinib does not inhibit or induce CYPs 1A2, 2C9 or 2C19.

Description:

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No Interaction Expected

Gefitinib

Alendronic acid

Quality of Evidence: Very Low

Summary:

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

Gefitinib

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. Gefitinib does not inhibit or induce CYP3A4.

Description:

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No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYP3A.

Description:

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No Interaction Expected

Gefitinib

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. Additionally, aliskiren is a substrate of P-gp. Gefitinib is unlikely to interfere with this elimination pathway and does not inhibit or induce P-gp.

Description:

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No Interaction Expected

Gefitinib

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. Gefitinib does not interact with this metabolic pathway.

Description:

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No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce these CYPs.

Description:

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No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYP3A4.

Description:

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Do Not Coadminister

Gefitinib

Aluminium hydroxide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be avoided. Aluminium hydroxide is not metabolised. Aluminium hydroxide may decrease gefitinib plasma concentrations due to elevation in gastric pH. After coadministration with ranitidine, a histamine H2-receptor antagonist, gefitinib exposure decreased by approximately 47%. A similar effect may occur after coadministration with aluminium hydroxide. Therefore, coadministration should be avoided. If coadministration is unavoidable, gefitinib should be administered at the moment at which the gastric pH is as low as possible and that is just before a new dose of aluminium hydroxide. Closely monitor gefitinib efficacy and, if available, gefitinib plasma concentrations.

Description:

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No Interaction Expected

Gefitinib

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 a substrate of P-gp. Gefitinib does not inhibit or induce UGTs, CYP3A4, CYP2C19 or P-gp.

Description:

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No Interaction Expected

Gefitinib

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. Gefitinib is unlikely to interfere with this elimination pathway.

Description:

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No Interaction Expected

Gefitinib

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. Gefitinib is unlikely to interfere with this elimination pathway and does not inhibit or induce OCT2.

Description:

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Potential Weak Interaction

Gefitinib

Amiodarone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Amiodarone is metabolised by CYP3A4 and CYP2C8. Gefitinib does not inhibit or induce CYP3A4 or CYP2C8. Moreover, the major metabolite of amiodarone, desethylamiodarone, is an inhibitor of CYPs 3A4 (weak), 2C9 (moderate), 2D6 (moderate), 2C19 (weak), 1A1 (strong), 2B6 (moderate) and P-gp (strong). Gefitinib concentrations may increase due to inhibition of CYP3A4, CYP2D6 and P-gp by desethylamiodarone. As the clinical relevance of these interactions is unknown, monitoring for gefitinib toxicity and, if available, gefitinib plasma concentrations may be required. 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

Gefitinib

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). Gefitinib is unlikely to interfere with this elimination pathway and does not inhibit or induce OCTs.

Description:

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Potential Interaction

Gefitinib

Amitriptyline

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Amitriptyline is metabolised predominantly by CYP2D6 and CYP2C19, with a small proportion metabolised by CYPs 3A4, 1A2 and 2C9. Gefitinib is a weak inhibitor of CYP2D6 and may increase amitriptyline concentrations. After coadministration of gefitinib with metoprolol, a sensitive CYP2D6 substrate, metoprolol exposure was increased by 35%. A similar effect may occur after coadministration with amitriptyline. If coadministration is unavoidable, monitor closely for amitriptyline toxicity. A dose reduction for amitriptyline may be required.

Description:

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No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYP3A4.

Description:

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No Interaction Expected

Gefitinib

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. Gefitinib is unlikely to interfere with this elimination pathway and does not inhibit or induce OATs.

Description:

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Potential Weak Interaction

Gefitinib

Amphotericin B

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Amphotericin B is not appreciably metabolised and is eliminated to a large extent in the bile. Gefitinib does not interfere with this metabolic or elimination pathway. However, the European SPC for amphotericin states that concomitant use of amphotericin B and antineoplastic agents can increase the risk of renal toxicity, bronchospasm and hypotension and so monitoring may be required.

Description:

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No Interaction Expected

Gefitinib

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 60-78% is excreted in the urine within 6 hours. Gefitinib is unlikely to interfere with this elimination pathway.

Description:

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No Interaction Expected

Gefitinib

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. Gefitinib does not interact with this metabolic pathway.

Description:

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Do Not Coadminister

Gefitinib

Antacids

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be avoided. Antacids are not metabolised by CYPs. Antacids may decrease gefitinib plasma concentrations due to elevation in gastric pH. After coadministration with ranitidine, a histamin H2-receptor antagonist, gefitinib exposure decreased by approximately 47%. A similar effect may occur after coadministration with antacids. Therefore, coadministration should be avoided. If coadministration is unavoidable, gefitinib should be administered at the moment at which the gastric pH is as low as possible and that is just before a new dose of antacids. Closely monitor gefitinib efficacy and, if available, gefitinib plasma concentrations.

Description:

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Potential Weak Interaction

Gefitinib

Apixaban

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. 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. Apixaban concentrations may increase due to in vitro BCRP inhibition by gefitinib. As the clinical relevance of this interaction is unknown, monitoring for apixaban toxicity and anti-Xa levels may be required.

Description:

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Potential Weak Interaction

Gefitinib

Aprepitant

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Aprepitant is mainly metabolized by CYP3A4 and to a lesser extent by CYP1A2 and CYP2C19. Gefitinib does not inhibit or induce CYPs 3A4, 1A2 or 2C19. During treatment aprepitant is a moderate inhibitor of CYP3A4. Gefitinib is metabolised by CYP3A4 and concentrations may increase due to inhibition by aprepitant. As the clinical relevance of this interaction is unknown monitoring for gefitinib toxicity and, if available, gefitinib plasma concentrations may be required. Moreover, after treatment aprepitant is a weak inducer of CYP3A4, CYP2C9 and UGT. Gefitinib concentrations may decrease due to CYP3A4 induction, however no clinically relevant effect on gefitinib exposure is expected.

Description:

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Potential Interaction

Gefitinib

Aripiprazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Aripiprazole is metabolised by CYP3A4 and CYP2D6. Gefitinib is a weak inhibitor of CYP2D6 and may increase concentrations of aripiprazole. After coadministration of gefitinib with metoprolol, a sensitive CYP2D6 substrate, metoprolol exposure was increased by 35%. A similar effect may occur after coadministration with aripiprazole. If coadministration is unavoidable, monitor closely for aripiprazole toxicity. A dose reduction for aripiprazole may be required.

Description:

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No Interaction Expected

Gefitinib

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)). Gefitinib is a weak inhibitor of CYP2D6 and may increase concentrations of asenapine. However, since CYP2D6 is a minor metabolic pathway, no clinically relevant effect on asenapine exposure is expected. Gefitinib does not inhibit or induce UGTs, CYP1A2 or CYP3A4.

Description:

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Potential Weak Interaction

Gefitinib

Astemizole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Astemizole is metabolised by CYPs 2D6, 2J2 and 3A4. Gefitinib is a weak inhibitor of CYP2D6 and may increase concentrations of astemizole. After coadministration of gefitinib with metoprolol, a sensitive CYP2D6 substrate, metoprolol exposure was increased by 35%. A similar effect may occur after coadministration with astemizole. As the clinical relevance of this interaction is unknown, monitoring for astemizole toxicity may be required.

Description:

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No Interaction Expected

Gefitinib

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. Gefitinib is unlikely to interfere with this elimination pathway.

Description:

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No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYP3A4, P-gp or OATP1B1.

Description:

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No Interaction Expected

Gefitinib

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. Gefitinib does not interact with this metabolic pathway.

Description:

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Potential Weak Interaction

Gefitinib

Azithromycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Azithromycin is mainly eliminated via biliary excretion; animal data suggest this may occur via P-gp and MRP2. Gefitinib does not inhibit or induce P-gp or MRP2. Azithromycin is also an inhibitor of P-gp. Gefitinib concentrations may increase due to P-gp inhibition by azithromycin. As the clinical relevance of this interaction is unknown, monitoring for gefitinib toxicity and, if available, gefitinib plasma concentrations may be required.

Description:

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No Interaction Expected

Gefitinib

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. Gefitinib does not interact with this metabolic pathway.

Description:

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No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYP3A4.

Description:

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No Interaction Expected

Gefitinib

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. Gefitinib is unlikely to interfere with this metabolic or elimination pathway.

Description:

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Potential Interaction

Gefitinib

Bepridil

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Bepridil is metabolised by CYP2D6 (major) and CYP3A4. Gefitinib does not inhibit or induce CYP3A4. Gefitinib is a weak inhibitor of CYP2D6 and may increase concentrations of bepridil. After coadministration of gefitinib with metoprolol, a sensitive CYP2D6 substrate, metoprolol exposure was increased by 35%. A similar effect may occur after coadministration with bepridil. If coadministration is unavoidable, monitor closely for bepridil toxicity. A dose reduction for bepridil may be required.

Description:

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No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYP3A4.

Description:

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No Interaction Expected

Gefitinib

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. Gefitinib is unlikely to interfere with bezafibrate metabolic or elimination pathway.

Description:

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No Interaction Expected

Gefitinib

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. Gefitinib is unlikely to interfere with this metabolic or elimination pathway.

Description:

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Potential Weak Interaction

Gefitinib

Bisoprolol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Bisoprolol is partly metabolised by CYP3A4 and CYP2D6, and partly eliminated unchanged in the urine. Gefitinib is a weak inhibitor of CYP2D6 and may increase concentrations of bisoprolol. After coadministration of gefitinib with metoprolol, a sensitive CYP2D6 substrate, metoprolol exposure was increased by 35%. A similar effect may occur after coadministration with bisoprolol. As the clinical relevance of this interaction is unknown, monitoring for bisoprolol toxicity and blood pressure may be required.

Description:

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Potential Interaction

Gefitinib

Bosentan

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Bosentan is a substrate and weak inducer of CYP3A4 and CYP2C9. Gefitinib does not inhibit or induce CYP3A4 or CYP2C9. Gefitinib is metabolised by CYP3A4 and concentrations may decrease due to induction by bosentan. Imatinib concentrations, on average, decreased by 33% in the presence of bosentan in a phase III clinical study. A similar effect may occur after coadministration with gefitinib. If coadministration is unavoidable, closely monitor gefitinib efficacy and, if available, gefitinib concentrations.

Description:

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No Interaction Expected

Gefitinib

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. Gefitinib is a weak inhibitor of CYP2D6 and may increase bromazepam concentrations. However, since bromazepam has a broad therapeutic window, no clinically relevant effect on bromazepam exposure is expected.

Description:

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No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYP3A4.

Description:

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No Interaction Expected

Gefitinib

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). Gefitinib does not inhibit or induce CYP3A4 or UGTs.

Description:

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Potential Interaction

Gefitinib

Bupropion

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Bupropion is primarily metabolised by CYP2B6 and is a strong inhibitor of CYP2D6. Gefitinib does not inhibit or induce CYP2B6. Gefitinib concentrations may increase due to CYP2D6 inhibition by bupropion. The clinical relevance of this interaction is unknown. However, gefitinib exposure increased 2-fold when administered to CYP2D6 poor metabolisers compared to CYP2D6 extensive metabolisers. A similar affect may occur after coadministration with bupropion. If coadministration is unavoidable, monitor closely for gefitinib toxicity and, if available, gefitinib plasma concentrations. No a priori dose adjustment is necessary for gefitinib.

Description:

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No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYP3A4.

Description:

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No Interaction Expected

Gefitinib

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. Gefitinib is unlikely to interfere with this elimination pathway.

Description:

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No Interaction Expected

Gefitinib

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. Gefitinib is unlikely to interfere with this elimination pathway.

Description:

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No Interaction Expected

Gefitinib

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. Gefitinib is unlikely to interfere with this elimination pathway.

Description:

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No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce OATs.

Description:

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Do Not Coadminister

Gefitinib

Carbamazepine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be avoided. Carbamazepine is primarily metabolized by CYP3A4 and to a lesser extent by CYP2C8. Gefitinib does not inhibit or induce CYP3A4 or CYP2C8. Moreover, carbamazepine is an inducer of CYP2C8 (strong), CYP2C9 (strong), CYP3A4 (strong), CYP1A2 (weak), CYP2B6, UGT1A1 and P-gp (moderate). Gefitinib is an in vitro substrate of P-gp and concentrations may decrease due to induction by carbamazepine, however, the clinical relevance of this interaction is unknown. Gefitinib is metabolised by CYP3A4 and concentrations may decrease due to induction by carbamazepine. After coadministration with rifampicin, a strong CYP3A4 inducer, gefitinib exposure decreased by 83%. A similar effect may occur after coadministration with carbamazepine. Therefore, coadministration should be avoided since a decrease in exposure can lead to decreased efficacy. If coadministration is unavoidable, a dose increase to 500 mg gefitinib once daily is recommended by the FDA product label. Closely monitor gefitinib efficacy and, if available, gefitinib plasma concentrations. Resume the 250 mg gefitinib dose taken prior to initiating carbamazepine 7 days after discontinuation of carbamazepine.

Description:

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Potential Weak Interaction

Gefitinib

Carvedilol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Carvedilol undergoes glucuronidation via UGTs 1A1, 2B4 and 2B7, and additionally metabolism via CYP2D6 and to a lesser extent CYPs 2C9 and 1A2. Gefitinib is a weak inhibitor of CYP2D6 and may increase concentrations of carvedilol. After coadministration of gefitinib with metoprolol, a sensitive CYP2D6 substrate, metoprolol exposure was increased by 35%. A similar effect may occur after coadministration with carvedilol. As the clinical relevance of this interaction is unknown, monitoring for carvedilol toxicity and blood pressure may be required. Carvedilol is also an inhibitor of P-gp and may increase gefitinib concentrations. As the clinical relevance of this interaction is unknown, monitoring for gefitinib toxicity and, if available, gefitinib plasma concentrations may be required.

Description:

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No Interaction Expected

Gefitinib

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. Gefitinib is unlikely to interact with this unspecified metabolic pathway.

Description:

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No Interaction Expected

Gefitinib

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. Gefitinib is unlikely to interfere with this elimination pathway and does not inhibit or induce OATs or MATEs.

Description:

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No Interaction Expected

Gefitinib

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. Gefitinib is unlikely to interfere with this elimination pathway and does not inhibit or induce OATs.

Description:

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No Interaction Expected

Gefitinib

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. Gefitinib is unlikely to interfere with this elimination pathway.

Description:

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No Interaction Expected

Gefitinib

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. Gefitinib is unlikely to interfere with this elimination pathway and does not inhibit or induce OATs.

Description:

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No Interaction Expected

Gefitinib

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. Gefitinib is unlikely to interfere with this elimination pathway.

Description:

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No Interaction Expected

Gefitinib

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. Gefitinib is unlikely to interfere with this elimination pathway.

Description:

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No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYP2C9.

Description:

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No Interaction Expected

Gefitinib

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. Gefitinib is unlikely to interfere with this metabolic or elimination pathway.

Description:

See Summary

Potential Interaction

Gefitinib

Chloramphenicol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Chloramphenicol is predominantly glucuronidated. Gefitinib does not inhibit or induce UGTs. In vitro studies have shown that chloramphenicol can inhibit metabolism mediated by CYP3A4 (strong), CYP2C19 (strong) and CYP2D6 (weak). Gefitinib is metabolised by both CYP3A4 (major) and CYP2D6 (minor) and concentrations may increase due to inhibition by chloramphenicol. The clinical relevance of CYP2D6 inhibition by is unknown. However, after coadministration with itraconazole, a strong CYP3A4 inhibitor, gefitinib exposure increased by 78%. A similar effect may occur after coadministration with chloramphenicol. The increase may even be higher in patients with CYP2D6 (minor pathway) poor metaboliser genotype. Therefore, coadministration should be approached with caution. If coadministration is unavoidable, monitor closely for gefitinib toxicity and, if available, gefitinib plasma concentrations. No a priori dose adjustment is necessary. 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

Gefitinib

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. Gefitinib does not inhibit or induce CYP3A4.

Description:

See Summary

Potential Weak Interaction

Gefitinib

Chlorphenamine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Chlorphenamine is predominantly metabolised in the liver via CYP2D6. Gefitinib is a weak inhibitor of CYP2D6 and may increase concentrations of chlorphenamine. After coadministration of gefitinib with metoprolol, a sensitive CYP2D6 substrate, metoprolol exposure was increased by 35%. A similar effect may occur after coadministration with chlorphenamine. As the clinical relevance of this interaction is unknown, monitoring for chlorphenamine toxicity may be required.

Description:

See Summary

Potential Weak Interaction

Gefitinib

Chlorpromazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Chlorpromazine is metabolised mainly by CYP2D6, but also by CYP1A2. Gefitinib is a weak inhibitor of CYP2D6 and may increase concentrations of chlorpromazine. After coadministration of gefitinib with metoprolol, a sensitive CYP2D6 substrate, metoprolol exposure was increased by 35%. A similar effect may occur after coadministration with chlorpromazine. As the clinical relevance of this interaction is unknown, monitoring for chlorpromazine toxicity may be required.

Description:

See Summary

No Interaction Expected

Gefitinib

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. 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. Gefitinib is unlikely to interfere with this elimination pathway and does not inhibit or induce OATs.

Description:

See Summary

Potential Weak Interaction

Gefitinib

Ciclosporin (Cyclosporine)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Ciclosporin is a substrate of CYP3A4 and P-gp. Gefitinib does not inhibit or induce CYP3A4 or P-gp. Ciclosporin is also an inhibitor of CYP3A4 and OATP1B1. Gefitinib is metabolised by CYP3A4 and concentrations may increase due to inhibition by ciclosporin. However, the clinical relevance of this interaction is unknown. Monitoring for gefitinib toxicity and, if available, gefitinib plasma concentrations may be required.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib is unlikely to interfere with this elimination pathway.

Description:

See Summary

Do Not Coadminister

Gefitinib

Cimetidine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be avoided. Cimetidine is metabolised by CYP450 enzymes. Gefitinib is a weak inhibitor of CYP2D6 and may increase concentrations of cimetidine. However, since multiple pathways are involved in the metabolism of cimetidine, no clinically relevant effect on cimetidine exposure is expected. In vitro data indicate that cimetidine inhibits OAT1 and OCT2 but at concentrations much higher than the observed clinical concentrations. Cimetidine is also a weak inhibitor of CYPs 3A4, 1A2, 2D6 and 2C19. Gefitinib is metabolised by both CYP3A4 (major) and CYP2D6 (minor) and concentrations may increase due to inhibition by cimetidine. As the clinical relevance of this interaction is unknown, monitoring for gefitinib toxicity and, if available, gefitinib plasma concentrations may be required. Furthermore, cimetidine may decrease gefitinib plasma concentrations due to elevation in gastric pH. After coadministration with ranitidine, a histamine H2-receptor antagonist, gefitinib exposure decreased by approximately 47%. A similar effect may occur after coadministration with cimetidine. Therefore, coadministration should be avoided. If coadministration is unavoidable, gefitinib should be administered at the moment at which acid secretion is inhibited the least and that is just before a new dose of cimetidine. Closely monitor gefitinib efficacy and, if available, gefitinib plasma concentrations.

Description:

See Summary

Potential Weak Interaction

Gefitinib

Ciprofloxacin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. 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. Gefitinib is unlikely to interfere with this metabolic or elimination pathway. Ciprofloxacin is also a weak to moderate inhibitor of CYP3A4 and a strong inhibitor of CYP1A2. Gefitinib is metabolised by CYP3A4 and concentrations may increase due to inhibition by ciprofloxacin. As the clinical relevance of this interaction is unknown, monitoring for gefitinib toxicity and, if available, gefitinib plasma concentrations may be required.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYP3A4.

Description:

See Summary

Potential Interaction

Gefitinib

Citalopram

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Citalopram is metabolised by CYPs 2C19 (38%), 2D6 (31%) and 3A4 (31%). Gefitinib is a weak inhibitor of CYP2D6 and may increase citalopram concentrations. After coadministration of gefitinib with metoprolol, a sensitive CYP2D6 substrate, metoprolol exposure was increased by 35%. A similar effect may occur after coadministration with citalopram. If coadministration is unavoidable, monitor closely for citalopram toxicity. A dose reduction for citalopram may be required.

Description:

See Summary

Potential Interaction

Gefitinib

Clarithromycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Clarithromycin is metabolised by CYP3A4. Gefitinib does not inhibit or induce CYP3A4. Clarithromycin is also an inhibitor of CYP3A4 (strong) and P-gp. Gefitinib concentrations may increase due to CYP3A4 and P-gp inhibition by clarithromycin. After coadministration with itraconazole, a strong CYP3A4 inhibitor, gefitinib exposure increased by 78%. A similar effect may occur after coadministration with clarithromycin. The increase in gefitinib exposure may be higher in patients with the CYP2D6 (minor pathway) poor metaboliser genotype. If coadministration is unavoidable, monitor closely for gefitinib toxicity and, if available, gefitinib plasma concentrations. No a priori dose adjustment is necessary for gefitinib.

Description:

See Summary

No Interaction Expected

Gefitinib

Clavulanic acid

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

Potential Weak Interaction

Gefitinib

Clemastine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Clemastine is predominantly metabolised in the liver via CYP2D6. Gefitinib is a weak inhibitor of CYP2D6 and may increase concentrations of clemastine. After coadministration of gefitinib with metoprolol, a sensitive CYP2D6 substrate, metoprolol exposure was increased by 35%. A similar effect may occur after coadministration with clemastine. As the clinical relevance of this interaction is unknown, monitoring for clemastine toxicity may be required.

Description:

See Summary

Potential Weak Interaction

Gefitinib

Clindamycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Clindamycin is metabolised by CYP3A4 and in vitro data suggest that it is a CYP3A4 inhibitor. Gefitinib does not inhibit or induce CYP3A4. Gefitinib is metabolised by CYP3A4 and concentrations may increase due to in vitro inhibition by clindamycin. As the clinical relevance of this interaction is unknown, monitoring for gefitinib toxicity and, if available, gefitinib plasma concentrations may be required.

Description:

See Summary

No Interaction Expected

Gefitinib

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 Weak Interaction

Gefitinib

Clofazimine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Clofazimine is largely excreted unchanged in the faeces. Gefitinib is unlikely to interfere with this elimination pathway. In vitro data suggest that clofazimine is a CYP3A4 inhibitor. Gefitinib is metabolised by CYP3A4 and concentrations may increase due to in vitro inhibition by clofazimine. As the clinical relevance of this interaction is unknown, monitoring for gefitinib toxicity and, if available, gefitinib plasma concentrations may be required.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce OATs.

Description:

See Summary

Potential Weak Interaction

Gefitinib

Clomipramine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Clomipramine is metabolised by CYPs 3A4, 1A2 and 2C19 to desmethylclomipramine, an active metabolite which has a higher activity than the parent drug. In addition, clomipramine and desmethylclomipramine are metabolised by CYP2D6. Gefitinib is a weak inhibitor of CYP2D6 and may increase clomipramine and desmethylclomipramine concentrations. After coadministration of gefitinib with metoprolol, a sensitive CYP2D6 substrate, metoprolol exposure was increased by 35%. A similar effect may occur after coadministration with clomipramine. The clinical relevance of this interaction is unknown. Monitoring for clomipramine toxicity may be required.

Description:

See Summary

No Interaction Expected

Gefitinib

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 the form of the unchanged parent drug (40-60% of the dose). Clonidine is also a weak inhibitor of OCT2. Gefitinib is unlikely to interfere with this metabolic or elimination pathway.

Description:

See Summary

No Interaction Expected

Gefitinib

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 CYP3A4, 2B6 and 1A2 playing a minor role. Moreover, clopidogrel is an inhibitor of CYP2C8 (strong), CYP2B6 (weak) and in vitro of CYP2C9 at high concentrations. The clinical relevance of CYP2C9 inhibition is unknown. Gefitinib does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYP3A4 or UGTs.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib is a weak inhibitor of CYP2D6 and may increase concentrations of clozapine. However, since CYP2D6 is a minor pathway, no clinically relevant effect on clozapine exposure is expected. Gefitinib does not inhibit or induce CYPs 1A2, 3A4 or 2C19.

Description:

See Summary

Potential Weak Interaction

Gefitinib

Codeine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Codeine is converted via CYP2D6 to morphine, an active metabolite with analgesic and opioid properties. 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. Additionally, the metabolite morphine is a substrate of P-gp. Gefitinib does not inhibit or induce CYP3A4 or P-gp. Gefitinib is a weak inhibitor of CYP2D6 and may increase morphine concentrations. After coadministration of gefitinib with metoprolol, a sensitive CYP2D6 substrate, metoprolol exposure was increased by 35%. A similar effect may occur after coadministration with codeine. As the clinical relevance of this interaction is unknown, monitoring for codeine toxicity may be required.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYP3A4 or P-gp.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce P-gp.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib is a weak inhibitor of CYP2D6 and may increase concentrations of dapsone. However, since multiple CYP450 enzymes are involved, no clinically relevant effect on dapsone exposure is expected.

Description:

See Summary

Potential Weak Interaction

Gefitinib

Desipramine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Desipramine is metabolised by CYP2D6. Gefitinib is weak inhibitor of CYP2D6 and may increase concentrations of desipramine. After coadministration of gefitinib with metoprolol, a sensitive CYP2D6 substrate, metoprolol exposure was increased by 35%. A similar effect may occur after coadministration with desipramine. As the clinical relevance of this interaction is unknown, monitoring for desipramine toxicity may be required.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYPs 2C9, 2C19 or 3A4.

Description:

See Summary

Potential Weak Interaction

Gefitinib

Dexamethasone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Dexamethasone is a substrate of CYP3A4. Gefitinib does not inhibit or induce CYP3A4. Dexamethasone has also been described as a weak inducer of CYP3A4. Gefitinib is metabolised by CYP3A4 and concentrations may decrease due to induction by dexamethasone. However, the clinical relevance of this interaction is unknown as the induction of CYP3A4 by dexamethasone has not yet been established. Monitoring of gefitinib efficacy and, if available, gefitinib plasma concentrations may be required.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYP3A4.

Description:

See Summary

No Interaction Expected

Gefitinib

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). Additionally, morphine is a substrate of P-gp. Gefitinib does not inhibit or induce UGTs or P-gp.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYP3A4, CYP2C19 or UGTs.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYP2C9 or UGTs.

Description:

See Summary

No Interaction Expected

Gefitinib

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 OATP4C1 and P-gp. Gefitinib does not inhibit or induce OATP4C1 or P-gp.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYP3A4 or UGTs.

Description:

See Summary

Potential Weak Interaction

Gefitinib

Diltiazem

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Diltiazem is metabolised by CYP3A4 and CYP2D6. Gefitinib is a weak inhibitor of CYP2D6 and may increase diltiazem concentrations. After coadministration of gefitinib with metoprolol, a sensitive CYP2D6 substrate, metoprolol exposure was increased by 35%. A similar effect may occur after coadministration with diltiazem. As the clinical relevance of this interaction is unknown, monitoring for diltiazem toxicity and blood pressure may be required. Diltiazem is also an inhibitor of CYP3A4 (moderate) and P-gp. Gefitinib concentrations may increase due to CYP3A4 and P-gp inhibition by diltiazem. As the clinical relevance of this interaction is unknown, monitoring for gefitinib toxicity and, if available, gefitinib plasma concentrations may be required.

Description:

See Summary

Potential Weak Interaction

Gefitinib

Diphenhydramine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Diphenhydramine is mainly metabolised by CYP2D6 and to a lesser extent by CYPs 1A2, 2C9 and 2C19. Gefitinib is a weak inhibitor of CYP2D6 and may increase concentrations of diphenhydramine. After coadministration of gefitinib with metoprolol, a sensitive CYP2D6 substrate, metoprolol exposure was increased by 35%. A similar effect may occur after coadministration with diphenhydramine. As the clinical relevance of this interaction is unknown, monitoring for diphenhydramine toxicity may be required. Additionally, diphenhydramine is a weak inhibitor of CYP2D6. Gefitinib concentrations may increase due to CYP2D6 inhibition by diphenhydramine. As the clinical relevance of this interaction is also unknown, monitoring for gefitinib toxicity and, if available, gefitinib plasma concentrations may be required.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce UGTs.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYP3A4 and is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Gefitinib

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%). Gefitinib is a weak inhibitor of CYP2D6 and may increase dolasetron concentrations. However, since CYP2D6 is a minor pathway, no clinically relevant effect on dolasetron exposure is expected.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYP3A4.

Description:

See Summary

No Interaction Expected

Gefitinib

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 gefitinib, or to be affected if coadministered with gefitinib.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYP3A4.

Description:

See Summary

Potential Interaction

Gefitinib

Doxepin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. 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. Gefitinib is a weak inhibitor of CYP2D6 and may increase concentrations of doxepin and nordoxepin. After coadministration of gefitinib with metoprolol, a sensitive CYP2D6 substrate, metoprolol exposure was increased by 35%. A similar effect may occur after coadministration with doxepin. If coadministration is unavoidable, monitor closely for doxepin toxicity. A dose reduction for doxepin may be required.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Between 40-60% of an administered dose can be accounted for in the urine. Gefitinib is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYP2C9 or CYP3A4.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYP3A4.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib 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

Potential Weak Interaction

Gefitinib

Duloxetine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Duloxetine is metabolised by CYP2D6 and CYP1A2. Gefitinib is a weak inhibitor of CYP2D6 and may increase duloxetine concentrations. After coadministration of gefitinib with metoprolol, a sensitive CYP2D6 substrate, metoprolol exposure was increased by 35%. A similar effect may occur after coadministration with duloxetine. As the clinical relevance of this reaction is unknown, monitoring for duloxetine toxicity may be required.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYP3A4.

Description:

See Summary

No Interaction Expected

Gefitinib

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). Gefitinib does not inhibit or induce CYP3A4.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYP3A4 or P-gp.

Description:

See Summary

No Interaction Expected

Gefitinib

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). Gefitinib does not inhibit or induce CYP1A2 or CYP2C8 or UGTs.

Description:

See Summary

No Interaction Expected

Gefitinib

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). Gefitinib is unlikely to interfere with this elimination pathway and does not inhibit or induce OATs.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib is unlikely to interfere with this elimination pathway.

Description:

See Summary

Potential Weak Interaction

Gefitinib

Erythromycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Erythromycin is a substrate of CYP3A4 and P-gp. Gefitinib does not inhibit or induce CYP3A4 or P-gp. Furthermore, erythromycin is an inhibitor of CYP3A4 (moderate) and P-gp. Gefitinib is metabolised by CYP3A4 and is an in vitro substrate of P-gp and concentrations may increase due to inhibition by erythromycin. As the clinical relevance of these interactions is unknown, monitoring for gefitinib toxicity and, if available, gefitinib plasma concentrations may be required.

Description:

See Summary

Potential Interaction

Gefitinib

Escitalopram

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Escitalopram is metabolised by CYPs 2C19 (37%), 2D6 (28%) and 3A4 (35%) to form N-desmethylescitalopram. Gefitinib is a weak inhibitor of CYP2D6 and may increase concentrations of escitalopram. After coadministration of gefitinib with metoprolol, a sensitive CYP2D6 substrate, metoprolol exposure was increased by 35%. A similar effect may occur after coadministration with escitalopram. If coadministration is unavoidable, monitor closely for escitalopram toxicity. A dose reduction for escitalopram may be required.

Description:

See Summary

Do Not Coadminister

Gefitinib

Esomeprazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be avoided. Esomeprazole is metabolised by CYP2C19 and CYP3A4. Esomeprazole is also an inhibitor of CYP2C19. Gefitinib does not interact with this metabolic pathway. However, esomeprazole may decrease gefitinib plasma concentrations due to elevation in gastric pH. After coadministration with ranitidine, a histamine H2-receptor antagonist, gefitinib exposure decreased by approximately 47%. A similar effect may occur after coadministration with esomeprazole. Therefore, coadministration should be avoided. If coadministration is unavoidable, gefitinib should be administered at the moment at which acid secretion is inhibited the least and that is just before a new dose of esomeprazole. Closely monitor gefitinib efficacy and, if available, gefitinib plasma concentrations.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYP3A4.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYP3A4, CYP1A2 or UGTs.

Description:

See Summary

No Interaction Expected

Gefitinib

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%). Gefitinib is unlikely to interfere with this metabolic or elimination pathway.

Description:

See Summary

No Interaction Expected

Gefitinib

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). Gefitinib does not inhibit or induce CYP3A4, CYP2C9 or UGTs.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYP3A4.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYP3A4 or P-gp.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib 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

Gefitinib

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 UGT1A1 and UGT1A3 and to a lesser extent by UGT2B15 and UGT2B7. Gefitinib does not inhibit or induce UGTs.

Description:

See Summary

Do Not Coadminister

Gefitinib

Famotidine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be avoided. Famotidine is excreted via OAT1/OAT3. Gefitinib does not inhibit or induce OATs. However, famotidine may decrease gefitinib plasma concentrations due to elevation in gastric pH. After coadministration with ranitidine, a histamine H2-receptor antagonist, gefitinib exposure decreased by approximately 47%. A similar effect may occur after coadministration with famotidine. Therefore, coadministration should be avoided. If coadministration is unavoidable, gefitinib should be administered at the moment at which acid secretion is inhibited the least and that is just before a new dose of famotidine. Closely monitor gefitinib efficacy and, if available, gefitinib plasma concentrations.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYP3A4.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYP3A4.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce P-gp.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYP3A4.

Description:

See Summary

No Interaction Expected

Gefitinib

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

Potential Interaction

Gefitinib

Flecainide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Flecainide is metabolised mainly via CYP2D6, with a proportion (approximately 30%) of the parent drug also eliminated unchanged renally. Gefitinib is unlikely to interfere with this elimination pathway. Gefitinib is a weak inhibitor of CYP2D6 and may increase concentrations of flecainide. After coadministration of gefitinib with metoprolol, a sensitive CYP2D6 substrate, metoprolol exposure was increased by 35%. A similar effect may occur after coadministration with flecainide. If coadministration is unavoidable, monitor closely for flecainide toxicity. A dose reduction for flecainide may be required.

Description:

See Summary

Potential Weak Interaction

Gefitinib

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. Gefitinib is unlikely to interfere with this elimination pathway and does not inhibit or induce OATs. Flucloxacillin is also described as a CYP3A4 inducer. Gefitinib is metabolised by CYP3A4 and concentrations may decrease due to induction by flucloxacillin. As the clinical relevance of this interaction is unknown, monitoring for gefitinib toxicity and, if available, gefitinib plasma concentrations may be required.

Description:

See Summary

Potential Weak Interaction

Gefitinib

Fluconazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Fluconazole is cleared primarily by renal excretion. Gefitinib is unlikely to interfere with this elimination pathway. Fluconaozle is also an inhibitor of CYPs 3A4 (moderate), 2C9 (moderate) and 2C19 (strong). Gefitinib is metabolised by CYP3A4 and concentrations may increase due to inhibition by fluconazole. As the clinical relevance of this interaction is unknown, monitoring for gefitinib toxicity and, if available, gefitinib plasma concentrations may be required.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYP3A.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYP3A4 or CYP2C19.

Description:

See Summary

Potential Interaction

Gefitinib

Fluoxetine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Fluoxetine is mainly metabolised by CYP2D6 and CYP2C9 and to a lesser extent by CYP2C19 and CYP3A4 to form norfluoxetine. Gefitinib is a weak inhibitor of CYP2D6 and may increase concentrations of fluoxetine. After coadministration of gefitinib with metoprolol, a sensitive CYP2D6 substrate, metoprolol exposure was increased by 35%. A similar effect may occur after coadministration with fluoxetine. If coadministration is unavoidable, monitor closely for fluoxetine toxicity. A dose reduction for fluoxetine may be required. Additionally, fluoxetine is a strong inhibitor of CYP2D6 and CYP2C19. Gefitinib concentrations may increase due to CYP2D6 inhibition by fluoxetine. The clinical relevance of this interaction is unknown. However, gefitinib exposure increased 2-fold when administered to CYP2D6 poor metabolisers compared to CYP2D6 extensive metabolisers. A similar affect may occur after coadministration with fluoxetine. If coadministration is unavoidable, monitor closely for gefitinib toxicity and, if available, gefitinib plasma concentrations. No a priori dose adjustment is necessary for gefitinib.

Description:

See Summary

Potential Weak Interaction

Gefitinib

Fluphenazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Fluphenazine is metabolised by CYP2D6. Gefitinib is a weak inhibitor of CYP2D6 and may increase concentrations of fluphenazine. After coadministration of gefitinib with metoprolol, a sensitive CYP2D6 substrate, metoprolol exposure was increased by 35%. A similar effect may occur after coadministration with fluphenazine. As the clinical relevance of this interaction is unknown, monitoring for fluphenazine toxicity may be required.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib is a weak inhibitor of CYP2D6 and may increase flurazepam concentrations. However, since flurazepam has a broad therapeutic window, no clinically relevant effect on flurazepam exposure is expected.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYP3A4.

Description:

See Summary

No Interaction Expected

Gefitinib

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%). Fluvastatin also potentially inhibits CYP2C9. However, the clinical relevance of CYP2C9 inhibition is unknown. Gefitinib does not interact with this metabolic pathway.

Description:

See Summary

Potential Weak Interaction

Gefitinib

Fluvoxamine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Fluvoxamine is metabolised mainly by CYP2D6 and to a lesser extent by CYP1A2. Gefitinib is a weak inhibitor of CYP2D6 and may increase concentrations of fluvoxamine. As the clinical relevance of this interaction is unknown, monitoring for fluvoxamine toxicity may be required. Fluvoxamine is also an inhibitor of CYPs 1A2 (strong), 2C19 (strong), 3A4 (moderate), 2C9 (weak-moderate) and CYP2D6 (weak). Gefitinib concentrations may increase due to CYP3A4 and CYP2D6 inhibition by fluvoxamine. As the clinical relevance of these interactions are also unknown, monitoring for gefitinib toxicity and, if available, gefitinib plasma concentrations may be required.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib is a weak inhibitor of CYP2D6 and may increase concentrations of formoterol. However, as multiple CYP450 and UGT enzymes are involved in formoterol metabolism, no clinically relevant effect on formoterol exposure is expected. Gefitinib does not inhibit or induce UGTs or CYP 2C19, 2C9 or 2A6.

Description:

See Summary

Potential Weak Interaction

Gefitinib

Fosaprepitant

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Fosaprepitant is rapidly, almost completely, converted to the active metabolite aprepitant. Gefitinib does not interact with this metabolic pathway. Aprepitant is mainly metabolized by CYP3A4 and to a lesser extent by CYP1A2 and CYP2C19. Gefitinib does not inhibit or induce CYP 3A4, 1A2 or 2C19. During treatment aprepitant is a moderate inhibitor of CYP3A4. Gefitinib is metabolised by CYP3A4 and concentrations may increase due to inhibition by aprepitant. As the clinical relevance of this interaction is unknown monitoring for gefitinib toxicity and, if available, gefitinib plasma concentrations may be required. Moreover, after treatment aprepitant is a weak inducer of CYP3A4, CYP2C9 and UGT. Gefitinib concentrations may decrease due to CYP3A4 induction, however no clinically relevant effect on gefitinib exposure is expected.

Description:

See Summary

Do Not Coadminister

Gefitinib

Fosphenytoin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be avoided. Fosphenytoin is rapidly converted to the active metabolite phenytoin. Gefitinib does not interact with this metabolic pathway. Phenytoin is mainly metabolized by CYP2C9 and to a lesser extent by CYP2C19. Gefitinib does not inhibit or induce CYP2C9 or CYP2C19. Phenytoin is a potent inducer of CYP3A4, UGT and P-gp. Gefitinib is metabolised by CYP3A4 and is an in vitro substrate of P-gp and concentrations may decrease due to induction by phenytoin. The clinical relevance of P-gp induction by phenytoin is unknown. However, after coadministration with rifampicin, a strong CYP3A4 inducer, gefitinib exposure decreased by 83%. A similar effect may occur after coadministration with fosphenytoin. Therefore, coadministration should be avoided since a decrease in exposure can lead to decreased efficacy. If coadministration is unavoidable, a dose increase to 500 mg gefitinib once daily is recommended by the FDA product label. Closely monitor gefitinib efficacy and, if available, gefitinib plasma concentrations. Resume the 250 mg gefitinib dose taken prior to initiating fosphenytoin 7 days after discontinuation of fosphenytoin.

Description:

See Summary

No Interaction Expected

Gefitinib

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). 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. Gefitinib is unlikely to interfere with this metabolic or elimination pathway.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Gefitinib

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 clinically relevant effect on CYP2C9. Gefitinib does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYPs 3A4, 2C9 or 2C19.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYP3A4 or CYP2C9.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYP2C9 or CYP2C19.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYP2C9.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYP2C9.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYP3A4 or P-gp.

Description:

See Summary

Do Not Coadminister

Gefitinib

Grapefruit juice

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is contraindicated. Grapefruit juice is known to inhibit CYP3A4 enzymes. Gefitinib is metabolised by CYP3A4 and concentrations may increase due to inhibition by grapefruit juice. After coadministration with itraconazole, a strong CYP3A4 inhibitor, gefitinib exposure increased by 78%. A similar effect may occur after coadministration with grapefruit juice. Therefore, coadministration is contraindicated.

Description:

See Summary

No Interaction Expected

Gefitinib

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

Gefitinib

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. Gefitinib is unlikely to interfere with this elimination pathway. 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 gefitinib. The clinical relevance of this interaction is unknown. If coadministration is unavoidable, closely monitor gefitinib efficacy and, if available, gefitinib concentrations.

Description:

See Summary

Potential Weak Interaction

Gefitinib

Haloperidol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Haloperidol has a complex metabolism as it undergoes glucuronidation (UGTs 2B7>1A4, 1A9), carbonyl reduction as well as oxidative metabolism (CYP3A4 and CYP2D6). Gefitinib is a weak inhibitor of CYP2D6 and may increase concentrations of haloperidol. After coadministration of gefitinib with metoprolol, a sensitive CYP2D6 substrate, metoprolol exposure was increased by 35%. A similar effect may occur after coadministration with haloperidol. As the clinical relevance of this interaction is unknown, monitoring for haloperidol toxicity may be required.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not interact with this metabolic pathway.

Description:

See Summary

Potential Weak Interaction

Gefitinib

Hydralazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Hydralazine is metabolised via primary oxidative metabolism and acetylation. Gefitinib 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 and may. Gefitinib is metabolised by CYP3A4 and concentrations may increase due to inhibition by hydralazine. However, the clinical relevance of this interaction is unknown. Monitoring for gefitinib toxicity and, if available, gefitinib plasma concentrations may be required.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib is unlikely to interfere with this elimination pathway and does not inhibit or induce OATs.

Description:

See Summary

Potential Weak Interaction

Gefitinib

Hydrocodone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Hydrocodone is metabolised by CYP2D6 to hydromorphone and by CYP3A4 to norhydrocodone, both of which have analgesic effects. Gefitinib does not inhibit or induce CYP3A4. Gefitinib is a weak inhibitor of CYP2D6 and may increase hydrocodone concentrations. After coadministration of gefitinib with metoprolol, a sensitive CYP2D6 substrate, metoprolol exposure was increased by 35%. A similar effect may occur after coadministration with hydrocodone. As the clinical relevance of this interaction is unknown, monitoring for hydrocodone toxicity may be required.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYP3A4.

Description:

See Summary

No Interaction Expected

Gefitinib

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

Gefitinib

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. Gefitinib does not inhibit or induce UGTs.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib is unlikely to interfere with this metabolic or elimination pathway.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not interact with this metabolic pathway.

Description:

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No Interaction Expected

Gefitinib

Ibandronic acid

Quality of Evidence: Very Low

Summary:

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

Gefitinib

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. Gefitinib does not inhibit or induce CYP2C9, CYP2C8 or UGTs.

Description:

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Potential Interaction

Gefitinib

Iloperidone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Iloperidone is metabolised by CYP3A4 and CYP2D6. Gefitinib is a weak inhibitor of CYP2D6 and may increase concentrations of iloperidone. After coadministration of gefitinib with metoprolol, a sensitive CYP2D6 substrate, metoprolol exposure was increased by 35%. A similar effect may occur after coadministration with iloperidone. If coadministration is unavoidable, monitor closely for iloperidone toxicity. A dose reduction for iloperidone may be required.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib is unlikely to interfere with this elimination pathway.

Description:

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Potential Weak Interaction

Gefitinib

Imipramine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Imipramine is metabolised by CYPs 3A4, 2C19 and 1A2 to desipramine. Imipramine and desipramine are both metabolised by CYP2D6. Gefitinib is a weak inhibitor of CYP2D6 and may increase concentrations of imipramine and desipramine. After coadministration of gefitinib with metoprolol, a sensitive CYP2D6 substrate, metoprolol exposure was increased by 35%. A similar effect may occur after coadministration with imipramine. As the clinical relevance of this interaction is unknown monitoring for imipramine toxicity may be required.

Description:

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No Interaction Expected

Gefitinib

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. Gefitinib is a weak inhibitor of CYP2D6 and may increase concentrations of indapamide. However, since multiple CYPs are involved in indapamide metabolism no clinically relevant effect on gefitinib exposure is expected. 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. Gefitinib does not inhibit or induce OATs.

Description:

See Summary

No Interaction Expected

Gefitinib

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

Gefitinib

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:

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No Interaction Expected

Gefitinib

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. Gefitinib is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not interact with this metabolic pathway.

Description:

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No Interaction Expected

Gefitinib

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). Gefitinib does not inhibit or induce UGTs or CYP2C9.

Description:

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No Interaction Expected

Gefitinib

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

Gefitinib

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. Gefitinib does not interact with this metabolic pathway.

Description:

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No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYP3A4.

Description:

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Potential Interaction

Gefitinib

Itraconazole

Quality of Evidence: Low

Summary:

Coadministration has been studied and should be approached with caution. Itraconazole is primarily metabolised by CYP3A4. Gefitinib does not inhibit or induce CYP3A4. Itraconazole is also an inhibitor of CYP3A4 (strong), CYP2C9 (weak), P-gp and BCRP. Gefitinib is a substrate of BCRP and P-gp and concentrations may increase due to inhibition by itraconazole, however, the clinical relevance of these interactions is unknown. Gefitinib is metabolised by CYP3A4 and concentrations will increase due to inhibition by itraconazole. In healthy male volunteers (n=23), coadministration of gefitinib (250 mg single dose) and itraconazole (200 mg daily for 12 days) increased gefitinib exposure by 78%. The increase in gefitnib exposure may be higher in patients with the CYP2D6 (minor pathway) poor metaboliser genotype. If coadministration is unavoidable, monitor closely for gefitinib toxicity and, if available, gefitinib plasma concentrations. No a priori dose adjustment is necessary.

Description:

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No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYP3A4.

Description:

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No Interaction Expected

Gefitinib

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. Gefitinib is unlikely to interfere with this elimination pathway.

Description:

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Potential Interaction

Gefitinib

Ketoconazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Ketoconazole is a substrate of CYP3A4. Gefitinib does not inhibit or induce CYP3A4. Ketoconazole is also an inhibitor of CYP3A4 (strong) and P-gp. Gefitinib is a substrate of P-gp and concentrations may increase due to inhibition by ketoconazole, however, the clinical relevance of this interaction is unknown. Gefitinib is metabolised by CYP3A4 and concentrations may increase due to inhibition by ketoconazole. After coadministration with itraconazole, a strong CYP3A4 inhibitor, gefitinib exposure increased by 78%. A similar effect may occur after coadministration with ketoconazole. The increase in gefitinib exposure may be higher in patients with the CYP2D6 (minor pathway) poor metaboliser genotype. If coadministration is unavoidable, monitor closely for gefitinib toxicity and, if available, gefitinib plasma concentrations. No a priori dose adjustment is necessary.

Description:

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No Interaction Expected

Gefitinib

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). Gefitinib does not inhibit or induce UGTs.

Description:

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No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYP3A4.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not interact with this metabolic pathway.

Description:

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Do Not Coadminister

Gefitinib

Lansoprazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be avoided. Lansoprazole is mainly metabolised by CYP2C19 and to a lesser extent by CYP3A4. Gefitinib does not inhibit or induce CYP2C19 or CYP3A4. However, lansoprazole may decrease gefitinib plasma concentrations due to elevation in gastric pH. After coadministration with ranitidine, a histamine H2-receptor antagonist, gefitinib exposure decreased by approximately 47%. A similar effect may occur after coadministration with lansoprazole. Therefore, coadministration should be avoided. If coadministration is unavoidable, gefitinib should be administered at the moment at which acid secretion is inhibited the least and that is just before a new dose of lansoprazole. Closely monitor gefitinib efficacy and, if available, gefitinib plasma concentrations.

Description:

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No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYP3A4.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib is unlikely to interfere with this metabolic or elimination pathway.

Description:

See Summary

No Interaction Expected

Gefitinib

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). Gefitinib is unlikely to interfere with this elimination pathway and does not inhibit or induce OCTs.

Description:

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Potential Weak Interaction

Gefitinib

Levomepromazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Levomepromazine is metabolised by CYP2D6. Gefitinib is a weak inhibitor of CYP2D6 and may increase concentrations of levomepromazine. After coadministration of gefitinib with metoprolol, a sensitive CYP2D6 substrate, metoprolol exposure was increased by 35%. A similar effect may occur after coadministration with levomepromazine. As the clinical relevance of this interaction is unknown, monitoring for levomepromazine toxicity may be required.

Description:

See Summary

No Interaction Expected

Gefitinib

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 is mainly metabolised by CYP3A4 and is glucuronidated to a minor extent. Gefitinib does not inhibit or induce CYP3A4 or UGTs.

Description:

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No Interaction Expected

Gefitinib

Levonorgestrel (Emergency Contraception)

Quality of Evidence: Very Low

Summary:

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not interact with this metabolic pathway.

Description:

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No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYP1A2 or CYP3A4.

Description:

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Potential Weak Interaction

Gefitinib

Linagliptin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Linagliptin is mainly eliminated as parent compound in faeces with metabolism by CYP3A4 representing a minor elimination pathway. Linagliptin is also a substrate of P-gp. Gefitinib does not inhibit or induce CYP3A4 or P-gp. Linagliptin is also a weak inhibitor of CYP3A4. Gefitinib is metabolised by CYP3A4 and concentrations may increase due to inhibition by linagliptin. As the clinical relevance of this interaction is unknown, monitoring for gefitinib toxicity and, if available, gefitinib plasma concentrations may be required.

Description:

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No Interaction Expected

Gefitinib

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. Gefitinib is unlikely to interfere with this unspecified metabolic pathway.

Description:

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No Interaction Expected

Gefitinib

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. Gefitinib does not interact with this metabolic pathway.

Description:

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No Interaction Expected

Gefitinib

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. Gefitinib is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Gefitinib

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:

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No Interaction Expected

Gefitinib

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, gefitinib is not an immunosuppressant, immunomodulatory or bone marrow toxic drug. Therefore, no pharmacodynamic interaction is expected with live vaccines.

Description:

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No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYP3A4, CYP2C8 or P-gp.

Description:

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No Interaction Expected

Gefitinib

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. Gefitinib is a weak inhibitor of CYP2D6 and may increase concentrations of loratadine. However, since CYP2D6 is a minor metabolic pathway, no clinically relevant effect on loratadine exposure is expected.

Description:

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No Interaction Expected

Gefitinib

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. Gefitinib is unlikely to interfere with this unspecified metabolic pathway.

Description:

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No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce UGTs.

Description:

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No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYP2C9.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYP3A4.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYPs 3A4, 2C19, 2C9 or 2C8.

Description:

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No Interaction Expected

Gefitinib

Magnesium

Quality of Evidence: Very Low

Summary:

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

Description:

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Potential Weak Interaction

Gefitinib

Maprotiline

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Maprotiline is mainly metabolised by CYP2D6. Gefitinib is a weak inhibitor of CYP2D6 and may increase concentrations of maprotiline. After coadministration of gefitinib with metoprolol, a sensitive CYP2D6 substrate, metoprolol exposure was increased by 35%. A similar effect may occur after coadministration with maprotiline. As the clinical relevance of this interaction is unknown monitoring for maprotiline toxicity may be required.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYP3A4.

Description:

See Summary

No Interaction Expected

Gefitinib

Medroxyprogesterone (non-depot)

Quality of Evidence: Very Low

Summary:

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYP2C9 or UGTs.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib is unlikely to interfere with this elimination pathway and does not inhibit or induce OATs.

Description:

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No Interaction Expected

Gefitinib

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. Gefitinib does not interact with this metabolic pathway.

Description:

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Potential Interaction

Gefitinib

Metamizole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Metamizole is metabolised by hydrolysis to the active metabolite MAA in the gastrointestinal tract. Metamizole is metabolised in serum and excreted via urine (90%) and faeces (10%). Gefitinib is unlikely to interfere with this metabolic or elimination pathway. Metamizole is also an inducer of CYP3A4. Gefitinib is metabolised by CYP3A4 and concentrations may decrease due to induction by metamizole. The clinical relevance of this interaction is unknown. If coadministration is unavoidable, closely monitor gefitinib efficacy and, if available, gefitinib plasma concentrations.

Description:

See Summary

No Interaction Expected

Gefitinib

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 a substrate of OCT1, OCT2, OCT3, MATE1 and MATE2K. Gefitinib does not inhibit or induce OCTs or MATEs.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYP3A4.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Gefitinib

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 clinically relevant extent and does not inhibit or induce CYP450s. Therefore, there is little potential for methylfenidate to affect disposition of gefitinib, or to be affected if coadministered with gefitinib.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYP3A4.

Description:

See Summary

Potential Weak Interaction

Gefitinib

Metoclopramide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Metoclopramide is partially metabolised by the CYP450 system (mainly CYP2D6). Gefitinib is a weak inhibitor of CYP2D6 and may increase concentrations of metoclopramide. After coadministration of gefitinib with metoprolol, a sensitive CYP2D6 substrate, metoprolol exposure was increased by 35%. A similar effect may occur after coadministration with metoclopramide. Monitoring for metoclopramide toxicity may be required.

Description:

See Summary

No Interaction Expected

Gefitinib

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. 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. Gefitinib is unlikely to interfere with this elimination pathway and does not inhibit or induce OATs.

Description:

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Potential Interaction

Gefitinib

Metoprolol

Quality of Evidence: Low

Summary:

Coadministration has been studied and should be approached with caution. Metoprolol is mainly metabolised by CYP2D6. Gefitinib is a weak inhibitor of CYP2D6 and will increase concentrations of metoprolol. In cancer patients (n=15), coadministration of metoprolol (50 mg single dose) and gefitinib (500 mg daily for 28 days) increased metoprolol exposure by 35%. If coadministration is unavoidable, monitor closely for metoprolol toxicity. A dose reduction for metoprolol may be required.

Description:

See Summary

Potential Weak Interaction

Gefitinib

Metronidazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Metronidazole is eliminated via glomerular filtration. Gefitinib is unlikely to interfere with this elimination pathway. Elevated plasma concentrations have been reported for some CYP3A substrates (e.g. tacrolimus, ciclosporin) with metronidazole. However, metronidazole did not increase concentrations of several CYP3A probe drugs (e.g. midazolam, alprazolam). Gefitinib is metabolised by CYP3A4. Gefitinib is metabolised by CYP3A4 and concentrations may increase due to inhibition by metronidazole. As the clinical relevance of this interaction is unknown, monitoring for gefitinib toxicity and, if available, gefitinib plasma concentrations may be required.

Description:

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Potential Interaction

Gefitinib

Mexiletine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Mexiletine is metabolised mainly by CYP2D6 and to a lesser extent by CYP1A2. Gefitinib does not inhibit or induce CYP1A2. Gefitinib is a weak inhibitor of CYP2D6 and may increase concentrations of mexiletine. After coadministration of gefitinib with metoprolol, a sensitive CYP2D6 substrate, metoprolol exposure was increased by 35%. A similar effect may occur after coadministration with mexiletine. If coadministration is unavoidable, monitor closely for mexiletine toxicity. A dose reduction for mexiletine may be required.

Description:

See Summary

Potential Weak Interaction

Gefitinib

Mianserin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Mianserin is metabolised by CYPs 2D6 and 1A2, and to a lesser extent by CYP3A4. Gefitinib is a weak inhibitor of CYP2D6 and may increase concentrations of mianserin. After coadministration of gefitinib with metoprolol, a sensitive CYP2D6 substrate, metoprolol exposure was increased by 35%. A similar effect may occur after coadministration with mianserin. As the clinical relevance of this interaction is unknown, monitoring for mianserin toxicity may be required.

Description:

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Potential Interaction

Gefitinib

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. Gefitinib is unlikely to interfere with this unspecified metabolic pathway. Miconazole is also an inhibitor of CYP2C9 (moderate) and CYP3A4 (strong). Gefitinib is metabolised by CYP3A4 and concentrations may increase due to inhibition by miconazole. After coadministration with itraconazole, a strong CYP3A4 inhibitor, gefitinib exposure increased by 78%. A similar effect may occur after coadministration with miconazole. The increase in gefitinib exposure may be higher in patients with the CYP2D6 (minor pathway) poor metaboliser genotype. If coadministration is unavoidable, monitor closely for gefitinib toxicity and, if available, gefitinib plasma concentrations. No a priori dose adjustment is necessary. Note: after dermal application miconazole is only minimally absorbed. Therefore, no clinically relevant interaction is expected.

Description:

See Summary

No Interaction Expected

Gefitinib

Midazolam (oral)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Midazolam is metabolised by CYP3A4. Gefitinib does not inhibit or induce CYP3A4.

Description:

See Summary

No Interaction Expected

Gefitinib

Midazolam (parenteral)

Quality of Evidence: Very Low

Summary:

Description:

See Summary

No Interaction Expected

Gefitinib

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%). Gefitinib is unlikely to interfere with this metabolic or elimination pathway.

Description:

See Summary

Potential Weak Interaction

Gefitinib

Mirtazapine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Mirtazapine is metabolised to 8-hydroxymirtazapine by CYP2D6 and CYP1A2, and to N-desmethylmirtazapine mainly by CYP3A4. Gefitinib is a weak inhibitor of CYP2D6 and may increase concentrations of mirtazapine. After coadministration of gefitinib with metoprolol, a sensitive CYP2D6 substrate, metoprolol exposure was increased by 35%. A similar effect may occur after coadministration with mirtazapine. As the clinical relevance of this interaction is unknown, monitoring for mirtazapine toxicity may be required.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYP3A4.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYP 2C8, 3A4 or 2C9.

Description:

See Summary

No Interaction Expected

Gefitinib

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). Morphine is also a substrate of P-gp. Gefitinib does not inhibit or induce UGTs or P-gp.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce UGTs.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYP2C9, CYP1A2 or UGTs.

Description:

See Summary

No Interaction Expected

Gefitinib

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%). Gefitinib does not inhibit or induce CYP2C9 or CYP3A4.

Description:

See Summary

Potential Weak Interaction

Gefitinib

Nebivolol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Nebivolol metabolism involves CYP2D6. Gefitinib is a weak inhibitor of CYP2D6 and may increase concentrations of nebivolol. After coadministration of gefitinib with metoprolol, a sensitive CYP2D6 substrate, metoprolol exposure was increased by 35%. A similar effect may occur after coadministration with nebivolol. As the clinical relevance of this interaction is unknown, monitoring for nebivolol toxicity and blood pressure may be required.

Description:

See Summary

Potential Interaction

Gefitinib

Nefazodone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Nefazodone is metabolised mainly by CYP3A4. Gefitinib does not inhibit or induce CYP3A4. Nefazodone is also a strong inhibitor of CYP3A4. Gefitinib concentrations may increase due to CYP3A4 inhibition by nefazodone. After coadministration with itraconazole, a strong CYP3A4 inhibitor, gefitinib exposure increased by 78%. A similar effect may occur after coadministration with nefazodone. The increase in gefitinib exposure may be higher in patients with the CYP2D6 (minor pathway) poor metaboliser genotype. If coadministration is unavoidable, monitor closely for gefitinib toxicity and, if available, gefitinib plasma concentrations. No a priori dose adjustment is necessary.

Description:

See Summary

Potential Weak Interaction

Gefitinib

Nicardipine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Nicardipine is metabolised mainly by CYP3A4 and to a lesser extent by CYP2D6 and CYP2C8. Gefitinib is a weak inhibitor of CYP2D6 and may increase concentrations of nicardipine. However, since CYP2D6 is a minor metabolic pathway, no clinically relevant effect on nicardipine exposure is expected. Nicardipine is also a weak inhibitor of CYP3A4. Gefitinib concentrations may increase due to inhibition of CYP3A4 by nicardipine. As the clinical relevance of this interaction is unknown, monitoring for gefitinib toxicity and, if available, gefitinib plasma concentrations may be required.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYP3A4.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYP2C9.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYP3A4.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYP3A4.

Description:

See Summary

No Interaction Expected

Gefitinib

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%). Gefitinib does not inhibit or induce UGTs and is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Gefitinib

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). Gefitinib does not inhibit or induce CYP3A4.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Norethisterone is extensively biotransformed, first by reduction and then by sulfate and glucuronide conjugation. Gefitinib does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYP3A4 or UGTs.

Description:

See Summary

Potential Interaction

Gefitinib

Nortriptyline

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Nortriptyline is metabolised mainly by CYP2D6. Gefitinib is a weak inhibitor of CYP2D6 and may increase concentrations of nortriptyline. After coadministration of gefitinib with metoprolol, a sensitive CYP2D6 substrate, metoprolol exposure was increased by 35%. A similar effect may occur after coadministration with nortriptyline. If coadministration is unavoidable, monitor closely for nortriptyline toxicity. A dose reduction for nortriptyline may be required.

Description:

See Summary

No Interaction Expected

Gefitinib

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

Gefitinib

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. Gefitinib is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Gefitinib

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). Gefitinib is a weak inhibitor of CYP2D6 and may increase concentrations of olanzapine. However, since CYP2D6 is a minor metabolic pathway, no clinically relevant effect on olanzapine exposure is expected. Gefitinib does not inhibit or induce CYP1A2 or UGTs,

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib is unlikely to interfere with this metabolic or elimination pathway.

Description:

See Summary

Do Not Coadminister

Gefitinib

Omeprazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be avoided. Omeprazole is mainly metabolised by CYP2C19 and to a lesser extent by CYP3A4. Omeprazole is also an inducer of CYP1A2 and an inhibitor of CYP2C19. Gefitinib does not interact with this metabolic pathway. However, omeprazole may decrease gefitinib plasma concentrations due to elevation in gastric pH. After coadministration with ranitidine, a histamine H2-receptor antagonist, gefitinib exposure decreased by approximately 47%. A similar effect may occur after coadministration with omeprazole. Therefore, coadministration should be avoided. If coadministration is unavoidable, gefitinib should be administered at the moment at which acid secretion is inhibited the least and that is just before a new dose of omeprazole. Closely monitor gefitinib efficacy and, if available, gefitinib plasma concentrations.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Additionally, ondansetron is a substrate of P-gp. Gefitinib is a weak inhibitor of CYP2D6 and may increase concentrations of ondansetron. However, since CYP2D6 is a minor metabolic pathway, no clinically relevant effect on ondansetron exposure is expected.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce UGTs.

Description:

See Summary

Potential Interaction

Gefitinib

Oxcarbazepine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Oxcarbazepine is extensively metabolized to the active metabolite monohydroxyderivate (MHD) through cytosolic enzymes. Gefitinib does not interact with this metabolic pathway. Both oxcarbazepine and MHD are inducers of CYP3A4 (moderate) and CYP3A5 and are also inhibitors of CYP2C19. Gefitinib concentrations may decrease due to CYP3A4 induction. The clinical relevance of this interaction is unknown. If coadministration is unavoidable, closely monitor gefitinib efficacy and, if available, gefitinib concentrations.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce UGTs.

Description:

See Summary

Potential Weak Interaction

Gefitinib

Oxycodone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Oxycodone is metabolised principally to noroxycodone via CYP3A and oxymorphone via CYP2D6. Gefitinib does not inhibit or induce CYP3A. Gefitinib is a weak inhibitor of CYP2D6 and may increase concentrations of oxycodone and may decrease concentrations of oxymorphone. After coadministration of gefitinib with metoprolol, a sensitive CYP2D6 substrate, metoprolol exposure was increased by 35%. A similar effect may occur after coadministration with oxycodone. As the clinical relevance of this interaction is unknown, monitoring for oxycodone toxicity may be required.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib is a weak inhibitor of CYP2D6 and may increase concentrations of paliperidone. However, since CYP2D6 is a minor metabolic pathway, no clinically relevant effect on paliperidone exposure is expected. Gefitinib does not inhibit or induce OCTs or CYP3A4.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Additionally, palonosetron is a substrate of P-gp. Gefitinib is a weak inhibitor of CYP2D6 and may increase concentrations of palonosetron. However, since CYP2D6 is a minor metabolic pathway, no clinically relevant effect on palonosetron exposure is expected.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib is unlikely to interfere with this elimination pathway.

Description:

See Summary

Do Not Coadminister

Gefitinib

Pantoprazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be avoided. Pantoprazole is mainly metabolised by CYP2C19 and to a lesser extent by CYPs 3A4, 2D6 and 2C9. Gefitinib is a weak inhibitor of CYP2D6 and may increase concentrations of pantoprazole. Since CYP2D6 is a minor metabolic pathway, no clinically relevant effect on pantoprazole exposure is expected. However, pantoprazole may decrease gefitinib plasma concentrations due to elevation in gastric pH. After coadministration with ranitidine, a histamine H2-receptor antagonist, gefitinib exposure decreased by approximately 47%. A similar effect may occur after coadministration with pantoprazole. Therefore, coadministration should be avoided. If coadministration is unavoidable, gefitinib should be administered at the moment at which acid secretion is inhibited the least and that is just before a new dose of pantoprazole. Closely monitor gefitinib efficacy and, if available, gefitinib plasma concentrations.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Gefitinib

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). Gefitinib does not inhibit or induce UGTs or CYPs 2E1, 1A2 or 3A4. Gefitinib is a weak inhibitor of CYP2D6 and may increase paracetamol concentrations. However, since CYP2D6 is a minor pathway, no clinically relevant effect on paracetamol exposure is expected.

Description:

See Summary

Potential Interaction

Gefitinib

Paroxetine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Paroxetine is mainly metabolised by CYP2D6. Gefitinib is a weak inhibitor of CYP2D6 and may increase concentrations of paroxetine. After coadministration of gefitinib with metoprolol, a sensitive CYP2D6 substrate, metoprolol exposure was increased by 35%. A similar effect may occur after coadministration with paroxetine. If coadministration is unavoidable, monitor closely for paroxetine toxicity. Moreover, paroxetine is an inhibitor of CYP2D6 (strong) and CYP2C9. Gefitinib concentrations may increase due to CYP2D6 inhibition by paroxetine. The clinical relevance of this interaction is unknown. However, gefitinib exposure increased 2-fold when administered to CYP2D6 poor metabolisers compared to CYP2D6 extensive metabolisers. A similar affect may occur after coadministration with paroxetine. If coadministration is unavoidable, monitor closely for gefitinib toxicity and, if available, gefitinib plasma concentrations. No a priori dose adjustment is necessary for gefitinib.

Description:

See Summary

No Interaction Expected

Gefitinib

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

Gefitinib

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 78% by tubular secretion via OAT). Gefitinib is unlikely to interfere with this elimination pathway and does not inhibit or induce OATs.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib is a weak inhibitor of CYP2D6 and may increase concentrations of perazine. However, since CYP2D6 is a minor metabolic pathway, no clinically relevant effect on perazine exposure is expected. Gefitinib does not inhibit or induce FMO3 or CYPs 1A3, 3A4, 2C19, 2C9 or 2E1.

Description:

See Summary

Potential Weak Interaction

Gefitinib

Periciazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. The metabolism of periciazine has not been well characterized but is likely to involve CYP2D6. Gefitinib is a weak inhibitor of CYP2D6 and may increase concentrations of periciazine. After coadministration of gefitinib with metoprolol, a sensitive CYP2D6 substrate, metoprolol exposure was increased by 35%. A similar effect may occur after coadministration with periciazine. As the clinical relevance of this interaction is unknown, monitoring for periciazine toxicity may be required.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib is unlikely to interfere with this metabolic or elimination pathway.

Description:

See Summary

Potential Weak Interaction

Gefitinib

Perphenazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Perphenazine is metabolised by CYP2D6. Gefitinib is a weak inhibitor of CYP2D6 and may increase concentrations of perphenazine. After coadministration of gefitinib with metoprolol, a sensitive CYP2D6 substrate, metoprolol exposure was increased by 35%. A similar effect may occur after coadministration with perphenazine. As the clinical relevance of this interaction is unknown, monitoring for perphenazine toxicity may be required.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYP2B6 or CYP3A4.

Description:

See Summary

No Interaction Expected

Gefitinib

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 by acetylation. Gefitinib does not interact with this metabolic pathway.

Description:

See Summary

Do Not Coadminister

Gefitinib

Phenobarbital (Phenobarbitone)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be avoided. Phenobarbital is metabolized by CYP2C19 and CYP2C9 (major pathway) and to a lesser extent by CYP2E1. Gefitinib does not inhibit or induce CYP2C19, CYP2C9 or CYP2E1. Phenobarbital is a strong inducer of CYP3A4, CYP2C9, CYP2C8 and UGTs. Gefitinib is metabolised by CYP3A4 and concentrations may decrease due to induction by phenobarbital. After coadministration with rifampicin, a strong CYP3A4 inducer, gefitinib exposure decreased by 83%. A similar effect may occur after coadministration with phenobarbital. Therefore, coadministration should be avoided since a decrease in exposure can lead to decreased efficacy. If coadministration is unavoidable, a dose increase to 500 mg gefitinib once daily is recommended by the FDA product label. Closely monitor gefitinib efficacy and, if available, gefitinib plasma concentrations. Resume the 250 mg gefitinib dose taken prior to initiating phenobarbital 7 days after discontinuation of phenobarbital.

Description:

See Summary

Potential Interaction

Gefitinib

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. Gefitinib does not inhibit or induce these CYP2C9 or CYP3A4. However, after coadministration of gefitinib with warfarin or acenocoumarol elevated INR and/or bleeding events have been reported. A similar effect may occur after coadministration with phenprocoumon. If coadministration is unavoidable, closely monitor INR/PT and signs of bleeding.

Description:

See Summary

Do Not Coadminister

Gefitinib

Phenytoin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be avoided. Phenytoin is mainly metabolized by CYP2C9 and to a lesser extent by CYP2C19. Gefitinib does not inhibit or induce CYP2C9 or CYP2C19. Phenytoin is a potent inducer of CYP3A4, UGT and P-gp. Gefitinib is an in vitro substrate of P-gp and concentrations may decrease due to induction by phenytoin, however, the clinical relevance of this interaction is unknown. Gefitinib is metabolised by CYP3A4 and concentrations may decrease due to induction by phenytoin. After coadministration with rifampicin, a strong CYP3A4 inducer, gefitinib exposure decreased by 83%. A similar effect may occur after coadministration with phenytoin. Therefore, coadministration should be avoided since a decrease in exposure can lead to decreased efficacy. If coadministration is unavoidable, a dose increase to 500 mg gefitinib once daily is recommended by the FDA product label. Closely monitor gefitinib efficacy and, if available, gefitinib plasma concentrations. Resume the 250 mg gefitinib dose taken prior to initiating phenytoin 7 days after discontinuation of phenytoin.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYP4F2.

Description:

See Summary

Potential Weak Interaction

Gefitinib

Pimozide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Pimozide is mainly metabolised by CYP3A4 and CYP2D6 and to a lesser extent by CYP1A2. Gefitinib is a weak inhibitor of CYP2D6 and may increase concentrations of pimozide. After coadministration of gefitinib with metoprolol, a sensitive CYP2D6 substrate, metoprolol exposure was increased by 35%. A similar effect may occur after coadministration with pimozide. As the clinical relevance of this interaction is unknown, monitoring for pimozide toxicity may be required.

Description:

See Summary

Potential Weak Interaction

Gefitinib

Pindolol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Pindolol is partly metabolised to hydroxymetabolites (possibly via CYP2D6) and partly eliminated unchanged in the urine. Gefitinib is a weak inhibitor of CYP2D6 and may increase concentrations of pindolol. After coadministration of gefitinib with metoprolol, a sensitive CYP2D6 substrate, metoprolol exposure was increased by 35%. A similar effect may occur after coadministration with pindolol. As the clinical relevance of this interaction is unknown, monitoring for pindolol toxicity and blood pressure may be required.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYPs 2C8, 3A4, 1A2 or 2C9.

Description:

See Summary

Potential Weak Interaction

Gefitinib

Pipotiazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. The metabolism of pipotiazine has not been well described but may involve CYP2D6. Gefitinib is a weak inhibitor of CYP2D6 and may increase concentrations of pipotiazine. After coadministration of gefitinib with metoprolol, a sensitive CYP2D6 substrate, metoprolol exposure was increased by 35%. A similar effect may occur after coadministration with pipotiazine. As the clinical relevance of this interaction is unknown, monitoring for pipotiazine toxicity may be required.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYP2C9.

Description:

See Summary

No Interaction Expected

Gefitinib

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 UGT1A3 and UGT2B7, with minimal metabolism by CYP2C9 and CYP2C8. Pitavastatin is also a substrate of OATP1B1. Gefitinib does not inhibit or induce these UGTs, CYP2C9, CYP2C8 or OATP1B1.

Description:

See Summary

Potential Interaction

Gefitinib

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. Gefitinib does not inhibit or induce P-gp or UGTs. Posaconazole is also a strong inhibitor of CYP3A4. Gefitinib is metabolized by CYP3A4 and concentrations may increase due to inhibition by posaconazole. After coadministration with itraconazole, a strong CYP3A4 inhibitor, gefitinib exposure increased by 78%. A similar effect may occur after coadministration with posaconazole. The increase in gefitinib exposure may be higher in patients with the CYP2D6 (minor pathway) poor metaboliser genotype. If coadministration is unavoidable, monitor closely for gefitinib toxicity and, if available, gefitinib plasma concentrations. No a priori dose adjustment is necessary.

Description:

See Summary

No Interaction Expected

Gefitinib

Potassium

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Potassium is eliminated renally. Gefitinib is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYPs 3A4, 2B6, 2C9 or 2C19.

Description:

See Summary

No Interaction Expected

Gefitinib

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 a substrate of OATP1B1. Gefitinib does not inhibit or induce OATP1B1.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYP3A4.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Prednisolone is then metabolised by CYP3A4. Gefitinib does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Gefitinib

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). Gefitinib is unlikely to interfere with this elimination pathway.

Description:

See Summary

Potential Weak Interaction

Gefitinib

Prochlorperazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Prochlorperazine is metabolised by CYP2D6 and CYP2C19. Gefitinib is a weak inhibitor of CYP2D6 and may increase concentrations of prochlorperazine. After coadministration of gefitinib with metoprolol, a sensitive CYP2D6 substrate, metoprolol exposure was increased by 35%. A similar effect may occur after coadministration with prochloperazine. Monitoring for prochlorperazine toxicity may be required.

Description:

See Summary

Potential Weak Interaction

Gefitinib

Promethazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Promethazine is metabolised by CYP2D6. Gefitinib is a weak inhibitor of CYP2D6 and may increase concentrations of promethazine. After coadministration of gefitinib with metoprolol, a sensitive CYP2D6 substrate, metoprolol exposure was increased by 35%. A similar effect may occur after coadministration with promethazine. As the clinical relevance of this interaction is unknown, monitoring for promethazine toxicity may be required.

Description:

See Summary

Potential Interaction

Gefitinib

Propafenone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Propafenone is metabolised mainly by CYP2D6 and to a lesser extent by CYP1A2 and CYP3A4. Gefitinib does not inhibit or induce CYP1A2 or CYP3A4. Gefitinib is a weak inhibitor of CYP2D6 and may increase concentrations of propafenone. After coadministration of gefitinib with metoprolol, a sensitive CYP2D6 substrate, metoprolol exposure was increased by 35%. A similar effect may occur after coadministration with propafenone. If coadministration is unavoidable, monitor closely for propafenone toxicity. A dose reduction for propafenone may be required.

Description:

See Summary

Potential Weak Interaction

Gefitinib

Propranolol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. 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). Gefitinib is a weak inhibitor of CYP2D6 and may increase concentrations of propanolol. After coadministration of gefitinib with metoprolol, a sensitive CYP2D6 substrate, metoprolol exposure was increased by 35%. A similar effect may occur after coadministration with propanolol. As the clinical relevance of this interaction is unknown, monitoring for pindolol toxicity and blood pressure may be required.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Additionally, prucalopride is a substrate of P-gp. Gefitinib is unlikely to interfere with this elimination pathway and does not inhibit or induce P-gp.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Gefitinib

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

Gefitinib

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. Gefitinib does not inhibit or induce CYP3A4.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib is unlikely to interfere with this metabolic or elimination pathway.

Description:

See Summary

Potential Interaction

Gefitinib

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. Quinidine is a substrate of P-gp. Gefitinib does not inhibit or induce P-gp or CYPs 3A4, 2C9 or 2E1. Quinidine is an inhibitor of CYP2D6 (strong), CYP3A4 (weak) and P-gp (moderate). Gefitinib concentrations may increase due to CYP2D6, CYP3A4 and P-gp inhibition by quinidine. The clinical relevance of these interactions is unknown. However, gefitinib exposure increased by 2-fold when administered to CYP2D6 poor metabolisers compared to extensive metabolisers. Coadministration with quinidine may also result in 2-fold increased gefitinib exposure. If coadministration is unavoidable, monitor closely for gefitinib toxicity and, if available, gefitinib plasma concentrations. No a priori dose adjustment is necessary for gefitinib.

Description:

See Summary

Do Not Coadminister

Gefitinib

Rabeprazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be avoided. Rabeprazole is mainly metabolised via non-enzymatic reduction and to a lesser extent by CYP2C19 and CYP3A4. Gefitinib does not inhibit or induce CYP2C19 or CYP3A4. However, rabeprazole may decrease gefitinib plasma concentrations due to elevation in gastric pH. After coadministration with ranitidine, a histamine H2-receptor antagonist, gefitinib exposure decreased by approximately 47%. A similar effect may occur after coadministration with rabeprazole. Therefore, coadministration should be avoided. If coadministration is unavoidable, gefitinib should be administered at the moment at which acid secretion is inhibited the least and that is just before a new dose of rabeprazole. Closely monitor gefitinib efficacy and, if available, gefitinib plasma concentrations.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not interact with this metabolic pathway.

Description:

See Summary

Do Not Coadminister

Gefitinib

Ranitidine

Quality of Evidence: Low

Summary:

Coadministration has been studied and should be avoided. Ranitidine is excreted via OAT1/OAT3. Gefitinib does not inhibit or induce OATs. In healthy male volunteers (n=26), coadministration of gefitinib (250 mg single dose) and ranitidine (450 mg) decreased gefitinib exposure by 47%. Therefore, coadministration should be avoided. If coadministration is unavoidable, gefitinib should be administered at the moment at which acid secretion is inhibited the least and that is just before a new dose of ranitidine. Closely monitor gefitinib efficacy and, if available, gefitinib plasma concentrations.

Description:

See Summary

Potential Weak Interaction

Gefitinib

Ranolazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Ranolazine is primarily metabolized by CYP3A4 and to a lesser extent by CYP2D6. Ranolazine is also a substrate of P-gp. Gefitinib is a weak inhibitor of CYP2D6 and may increase concentrations of ranolazine. However, since CYP2D6 is a minor metabolic pathway, no clinically relevant effect on ranolazine exposure is expected. Ranolazine is also a weak inhibitor of P-gp, CYP3A4 and CYP2D6. Gefitinib is an in vitro substrate of P-gp and is metabolised by both CYP3A4 (major) and CYP2D6 (minor), and concentrations may increase due to inhibition by ranolazine. However, the clinical relevance of these interactions is unknown. Monitoring for gefitinib toxicity and, if available, gefitinib plasma concentrations may be required.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYP3A4. In vitro data indicate reboxetine to be a weak inhibitor of CYP3A4 but in vivo data showed no inhibitory effect on CYP3A4. Therefore, no clinically relevant effect on gefitinib exposure is expected.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYP2C8, CYP3A4 or OATP1B1.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Gefitinib

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

Gefitinib

Rifabutin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be avoided. Rifabutin is metabolised by CYP3A4 and via deacetylation. Gefitinib does not inhibit or induce CYP3A4. Rifabutin is also a strong CYP3A4 and P-gp inducer. Gefitinib is an in vitro substrate of P-gp and concentrations may decrease due to induction by rifabutin, however the clinical relevance of this interaction is unknown. Gefitinib is metabolised by CYP3A4 and concentrations may decrease due to induction by rifabutin. After coadministration with rifampicin, a strong CYP3A4 inducer, gefitinib exposure decreased by 83%. A similar effect may occur after coadministration with rifabutin. Therefore, coadministration should be avoided since a decrease in exposure can lead to decreased efficacy. If coadministration is unavoidable, a dose increase to 500 mg gefitinib once daily is recommended by the FDA product label. Closely monitor gefitinib efficacy and, if available, gefitinib plasma concentrations. Resume the 250 mg gefitinib dose taken prior to initiating rifapentine 7 days after discontinuation of rifapentine.

Description:

See Summary

Do Not Coadminister

Gefitinib

Rifampicin

Quality of Evidence: Moderate

Summary:

Coadministration has been studied and should be avoided. Rifampicin is metabolised via deacetylation. Gefitinib does not interact with this metabolic pathway. Rifampicin is also a strong CYP3A4 and P-gp inducer. Gefitinib is metabolised by CYP3A4 and concentrations will decrease due to induction by rifampicin. In healthy male volunteers (n=18), coadministration of gefitinib (500 mg single dose) and rifampicin (600 mg daily for 16 days) decreased gefitinib exposure by 83%. Therefore, coadministration should be avoided since a decrease in exposure can lead to decreased efficacy. If coadministration is unavoidable, a dose increase to 500 mg gefitinib once daily is recommended by the FDA product label. Closely monitor gefitinib efficacy and, if available, gefitinib plasma concentrations. Resume the 250 mg gefitinib dose taken prior to initiating rifapentine 7 days after discontinuation of rifapentine.

Description:

See Summary

Do Not Coadminister

Gefitinib

Rifapentine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be avoided. Rifapentine is metabolised via deacetylation. Gefitinib does not interact with this metabolic pathway. Rifapentine is also a strong CYP3A4, CYP2C8 and P-gp inducer. Gefitinib is metabolised by CYP3A4 and concentrations may decrease due to induction by rifapentine. After coadministration with rifampicin, gefitinib exposure decreased by 83%. Therefore, coadministration should be avoided since a decrease in exposure can lead to decreased efficacy. If coadministration is unavoidable, a dose increase to 500 mg gefitinib once daily is recommended by the FDA product label. Closely monitor gefitinib efficacy and, if available, gefitinib plasma concentrations. Resume the 250 mg gefitinib dose taken prior to initiating rifapentine 7 days after discontinuation of rifapentine.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib is unlikely to interfere with this elimination pathway.

Description:

See Summary

Potential Weak Interaction

Gefitinib

Risperidone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Risperidone is metabolised by CYP2D6 and to a lesser extent by CYP3A4. Gefitinib is a weak inhibitor of CYP2D6 and may increase concentrations of risperidone. After coadministration of gefitinib with metoprolol, a sensitive CYP2D6 substrate, metoprolol exposure was increased by 35%. A similar effect may occur after coadministration with risperidone. As the clinical relevance of this interaction is unknown, monitoring for risperidone toxicity may be required. Risperidone is also a substrate of P-gp. Gefitinib does not inhibit or induce P-gp.

Description:

See Summary

Potential Weak Interaction

Gefitinib

Rivaroxaban

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Rivaroxaban is partly metabolised in the liver (by CYP3A4, CYP2J2 and hydrolytic enzymes) and partly eliminated unchanged in urine. Rivaroxaban is also substrate of P-gp and BCRP. Rivaroxaban concentrations may increase due to in vitro BCRP inhibition by gefitinib. As the clinical relevance of this interaction is unknown, monitoring for rivaroxaban toxicity and anti-Xa activity may be required.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYP2C8 or CYP2C9.

Description:

See Summary

Potential Weak Interaction

Gefitinib

Rosuvastatin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Rosuvastatin is largely excreted unchanged in the faeces via OATP1B1 and is a substrate of BCRP. Gefitinib is an in vitro inhibitor of BCRP and may increase concentrations of rosuvastatin. The clinical relevance of this interaction is unknown. Monitoring for rosuvastatin toxicity may be required. Gefitinib does not inhibit or induce OATP1B1.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Gefitinib

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. However, systemic exposure of salmeterol is low. Gefitinib does not inhibit or induce CYP3A4.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYP3A4 or P-gp.

Description:

See Summary

No Interaction Expected

Gefitinib

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

Potential Interaction

Gefitinib

Sertindole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Sertindole is metabolised by CYP2D6 and CYP3A4. Gefitinib is a weak inhibitor of CYP2D6 and may increase concentrations of sertindole. After coadministration of gefitinib with metoprolol, a sensitive CYP2D6 substrate, metoprolol exposure was increased by 35%. A similar effect may occur after coadministration with sertindole. If coadministration is unavoidable, monitor closely for sertindole toxicity. A dose reduction for sertindole may be required.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib is a weak inhibitor of CYP2D6 and may increase sertraline concentrations. However, since CYP2D6 is a minor pathway, no clinically relevant effect on sertraline exposure is expected. Gefitinib does not inhibit or induce CYPs 2B6, 2C9, 2C19 or 3A4.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYP3A4 or CYP2C9.

Description:

See Summary

Potential Weak Interaction

Gefitinib

Simvastatin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Simvastatin is metabolised by CYP3A4. Simvastatin is also a substrate of BCRP and the active metabolite is a substrate of OATP1B1. Gefitinib is an in vitro inhibitor of BCRP and may increase concentrations of simvastatin. The clinical relevance of this interaction is unknown. Monitoring for simvastatin toxicity may be required. Gefitinib does not inhibit or induce CYP3A4 or OATP1B1.

Description:

See Summary

No Interaction Expected

Gefitinib

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 a substrate of P-gp. Gefitinib does not inhibit or induce CYP3A4 or P-gp.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce OATs, P-gp or CYP3A4.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib is unlikely to interfere with this unspecified metabolic pathway.

Description:

See Summary

Do Not Coadminister

Gefitinib

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. Gefitinib is metabolised by CYP3A4 and concentrations may decrease due to induction by St John’s wort. After coadministration with rifampicin, a strong CYP3A4 inducer, gefitinib exposure decreased by 83%. A similar effect may occur after coadministration with St John’s Wort. Therefore, coadministration is contraindicated.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib is unlikely to interfere with this metabolic or elimination pathway.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYP2C9.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Gefitinib

Tacrolimus

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tacrolimus is metabolised mainly by CYP3A4. Gefitinib does not inhibit or induce CYP3A4. 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. Therefore, no clinically relevant effect on gefitinib exposure is expected.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYP3A4.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib is a weak inhibitor of CYP2D6 and may increase concentrations of tamsulosin. However, since CYP2D6 is a minor metabolic pathway, no clinically relevant effect on tamsulosin exposure is expected.

Description:

See Summary

No Interaction Expected

Gefitinib

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 78%) and inactive metabolite (approximately 20%) in the urine. Gefitinib is unlikely to interfere with this elimination pathway.

Description:

See Summary

Potential Interaction

Gefitinib

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. Gefitinib does not inhibit or induce CYP3A4. Telithromycin is also an inhibitor of CYP3A4 (strong) and P-gp. The clinical relevance of P-gp inhibition by telithromycin is unknown. However, gefitinib is metabolised by CYP3A4 and concentrations may increase due to inhibition by telithromycin. After coadministration with itraconazole, a strong CYP3A4 inhibitor, gefitinib exposure increased by 78%. A similar effect may occur after coadministration with telithromycin. If coadministration is unavoidable, monitor closely for gefitinib toxicity and, if available, gefitinib plasma concentrations. No a priori dose adjustment is necessary.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce UGTs.

Description:

See Summary

No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce UGTs.

Description:

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Potential Interaction

Gefitinib

Terbinafine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Terbinafine is metabolised by CYPs 1A2, 2C9, 3A4 and to a lesser extent by CYP2C8 and CYP2C19. Gefitinib does not inhibit or induce CYPs 1A2, 2C9, 3A4, 2C8 or 2C19. Terbinafine is also a moderate-strong inhibitor of CYP2D6. Gefitinib is to a lesser extent metabolised by CYP2D6 and concentrations may increase due to inhibition by terbinafine. The clinical relevance of this interaction is unknown. However, gefitinib exposure increased by 2-fold when administered to CYP2D6 poor metabolisers compared to extensive metabolisers. Coadministration with terbinafine may also result in 2-fold increased gefitinib exposure. If coadministration is unavoidable, monitor closely for gefitinib toxicity and, if available, gefitinib plasma concentrations. No a priori dose adjustment is necessary for gefitinib

Description:

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No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYP3A4.

Description:

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No Interaction Expected

Gefitinib

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. Gefitinib is unlikely to interfere with this elimination pathway.

Description:

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No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYP1A2.

Description:

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No Interaction Expected

Gefitinib

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:

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Potential Weak Interaction

Gefitinib

Thioridazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Thioridazine is metabolised by CYP2D6 and to a lesser extent by CYP3A4. Gefitinib is a weak inhibitor of CYP2D6 and may increase concentrations of thioridazine. After coadministration of gefitinib with metoprolol, a sensitive CYP2D6 substrate, metoprolol exposure was increased by 35%. A similar effect may occur after coadministration with thioridazine. As the clinical relevance of this interaction is unknown, monitoring for thioridazine toxicity may be required.

Description:

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No Interaction Expected

Gefitinib

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. Gefitinib is unlikely to interfere with this elimination pathway.

Description:

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Potential Weak Interaction

Gefitinib

Ticagrelor

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Ticagrelor is a substrate of CYP3A4 and P-gp. Gefitinib does not inhibit or induce CYP3A4 or P-gp. Ticagrelor is also a weak inhibitor of CYP3A4. Gefitinib is metabolised by CYP3A4 and concentrations may increase due to inhibition by ticagrelor. As the clinical relevance of this interaction is unknown, monitoring for gefitinib toxicity and, if available, gefitinib plasma concentrations may be required.

Description:

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Potential Weak Interaction

Gefitinib

Timolol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Timolol is predominantly metabolised in the liver by CYP2D6. Gefitinib is a weak inhibitor of CYP2D6 and may increase concentrations of timolol. After coadministration of gefitinib with metoprolol, a sensitive CYP2D6 substrate, metoprolol exposure was increased by 35%. A similar effect may occur after coadministration with timolol. As the clinical relevance of this interaction is unknown, monitoring for timolol toxicity and blood pressure may be required.

Description:

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No Interaction Expected

Gefitinib

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. Gefitinib is unlikely to interfere with this elimination pathway.

Description:

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No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYPs 2C9, 2C8 or 2C19.

Description:

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Potential Interaction

Gefitinib

Tolterodine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Tolterodine is primarily metabolised by CYP2D6 with CYP3A4 playing a minor role. Gefitinib is a weak inhibitor of CYP2D6 and may increase concentrations of tolterodine. After coadministration of gefitinib with metoprolol, a sensitive CYP2D6 substrate, metoprolol exposure was increased by 35%. A similar effect may occur after coadministration with tolterodine. If coadministration is unavoidable, monitor closely for tolterodine toxicity. A dose reduction for tolterodine may be required.

Description:

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No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYP2C9 or OATs.

Description:

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Potential Weak Interaction

Gefitinib

Tramadol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Tramadol is metabolised by CYPs 3A4, 2B6, and 2D6. Gefitinib does not inhibit or induce CYP3A4 or CYP2B6. Gefitinib is a weak inhibitor of CYP2D6 and may increase concentrations of tramadol. After coadministration of gefitinib with metoprolol, a sensitive CYP2D6 substrate, metoprolol exposure was increased by 35%. A similar effect may occur after coadministration with tramadol. As the clinical relevance of this interaction is unknown, monitoring for tramadol toxicity may be required.

Description:

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No Interaction Expected

Gefitinib

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. Gefitinib does not interact with this metabolic pathway.

Description:

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No Interaction Expected

Gefitinib

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. Gefitinib is unlikely to interfere with this elimination pathway.

Description:

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No Interaction Expected

Gefitinib

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. Gefitinib does not interact with this metabolic pathway.

Description:

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No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYP3A4.

Description:

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No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYP3A4.

Description:

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No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYP3A4.

Description:

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No Interaction Expected

Gefitinib

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. To a lesser extent (approximately 30%) trimethoprim is metabolised by CYP enzymes (in vitro data suggest CYPs 3A4, 1A2 and 2C9). Sulfamethoxazole is metabolised by CYP2C9. Furthermore, trimethoprim is 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. Gefitinib is unlikely to interfere with these metabolic or elimination pathways.

Description:

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Potential Interaction

Gefitinib

Trimipramine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Trimipramine is metabolised mainly by CYP2D6. Gefitinib is a weak inhibitor of CYP2D6 and may increase concentrations of trimipramine. After coadministration of gefitinib with metoprolol, a sensitive CYP2D6 substrate, metoprolol exposure was increased by 35%. A similar effect may occur after coadministration with trimipramine. If coadministration is unavoidable, monitor closely for trimipramine toxicity. A dose reduction for trimipramine may be required.

Description:

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Potential Weak Interaction

Gefitinib

Tropisetron

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Tropisetron is metabolised mainly by CYP2D6. Gefitinib is a weak inhibitor of CYP2D6 and may increase concentrations of tropisetron. After coadministration of gefitinib with metoprolol, a sensitive CYP2D6 substrate, metoprolol exposure was increased by 35%. A similar effect may occur after coadministration with tropisetron. Monitoring for tropisetron toxicity may be required. Additionally, tropisetron is a substrate of P-gp. Gefitinib does not inhibit or induce P-gp.

Description:

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No Interaction Expected

Gefitinib

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 by CYP1A2 and CYP2D6. Gefitinib is a weak inhibitor of CYP2D6 and may increase ulipristal concentrations. However, since CYP2D6 is a minor pathway, no clinically relevant effect on ulipristal exposure is expected.

Description:

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No Interaction Expected

Gefitinib

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. Gefitinib does not interact with this metabolic pathway.

Description:

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No Interaction Expected

Gefitinib

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. Gefitinib is unlikely to interfere with this elimination pathway.

Description:

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No Interaction Expected

Gefitinib

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. Gefitinib is unlikely to interfere with this elimination pathway.

Description:

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Potential Weak Interaction

Gefitinib

Venlafaxine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Venlafaxine is mainly metabolised by CYP2D6 and to a lesser extent by CYPs 3A4, 2C19 and 2C9. Gefitinib is a weak inhibitor of CYP2D6 and may increase concentrations of venlafaxine. After coadministration of gefitinib with metoprolol, a sensitive CYP2D6 substrate, metoprolol exposure was increased by 35%. A similar effect may occur after coadministration with venlafaxine. As the clinical relevance of this interaction is unknown, monitoring for venlafaxine toxicity may be required.

Description:

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Potential Weak Interaction

Gefitinib

Verapamil

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Verapamil is metabolised mainly by CYP3A4 and to a lesser extent by CYPs 1A2, 2C8 and 2C9. Gefitinib does not inhibit or induce CYP 3A4, 1A2, 2C8 or 2C9. Verapamil is also an inhibitor of CYP3A4 (moderate) and P-gp (strong). Gefitinib concentrations may increase due to CYP3A4 and P-gp inhibition by verapamil. As the clinical relevance of this interaction is unknown, monitoring for gefitinib toxicity and, if available, gefitinib plasma concentrations may be required.

Description:

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No Interaction Expected

Gefitinib

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. Gefitinib is unlikely to interfere with this metabolic pathway and does not inhibit or induce P-gp.

Description:

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No Interaction Expected

Gefitinib

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:

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Potential Interaction

Gefitinib

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. Gefitinib does not inhibit CYPs 2C19, 3A4 or 2C9. Voriconazole is also a strong inhibitor of CYP3A4 and a weak inhibitor of CYPs 2C9, 2C19 and 2B6. Gefitinib is metabolised by CYP3A4 and concentrations may increase due to inhibition by voriconazole. After coadministration with itraconazole, a strong CYP3A4 inhibitor, gefitinib exposure increased by 78%. A similar effect may occur after coadministration with voriconazole. The increase in gefitinib exposure may be higher in patients with the CYP2D6 (minor pathway) poor metaboliser genotype. If coadministration is unavoidable, monitor closely for gefitinib toxicity and, if available, gefitinib plasma concentrations. No a priori dose adjustment is necessary.

Description:

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Potential Interaction

Gefitinib

Warfarin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Warfarin is a mixture of enantiomers which are metabolised by different cytochromes. R-warfarin is primarily metabolised by CYP1A2 and CYP3A4. S-warfarin (more potent) is metabolised by CYP2C9. Gefitinib does not inhibit or induce CYPs 1A2, 3A4 or 2C9. However, after coadministration of gefitinib with warfarin elevated INR and/or bleeding events have been reported. If coadministration is unavoidable, closely monitor INR/PT and signs of bleeding.

Description:

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No Interaction Expected

Gefitinib

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. Gefitinib is unlikely to interfere with this metabolic or elimination pathway and does not inhibit or induce OATs.

Description:

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No Interaction Expected

Gefitinib

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. Gefitinib does not interact with this metabolic pathway.

Description:

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No Interaction Expected

Gefitinib

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). Gefitinib does not inhibit or induce CYP3A4.

Description:

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No Interaction Expected

Gefitinib

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. Gefitinib is unlikely to interfere with this elimination pathway.

Description:

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No Interaction Expected

Gefitinib

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. Gefitinib is a weak inhibitor of CYP2D6 and may increase concentrations of zolpidem. However, since CYP2D6 is a minor metabolic pathway, no clinically relevant effect on zolpidem exposure is expected.

Description:

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No Interaction Expected

Gefitinib

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. Gefitinib does not inhibit or induce CYP3A4 or CYP2C8.

Description:

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No Interaction Expected

Gefitinib

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. Gefitinib is a weak inhibitor of CYP2D6 and may increase concentrations of zotepine. However, since CYP2D6 is a minor metabolic pathway, no clinically relevant effect on zotepine exposure is expected. Gefitinb does not inhibit or induce CYP3A4 or CYP1A2.

Description:

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Potential Weak Interaction

Gefitinib

Zuclopenthixol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Zuclopenthixol is metabolised by sulphoxidation, N-dealkylation (via CYP2D6 and CYP3A4) and glucuronidation. Gefitinib is a weak inhibitor of CYP2D6 and may increase concentrations of zuclopenthixol. After coadministration of gefitinib with metoprolol, a sensitive CYP2D6 substrate, metoprolol exposure was increased by 35%. A similar effect may occur after coadministration with zuclopenthixol. As the clinical relevance of this interaction is unknown, monitoring for zuclopenthixol toxicity may be required.

Description:

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