Cancer Drug Interactions from Radboud UMC and University of Liverpool

No Interaction Expected

Irinotecan

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. Irinotecan does not interact with this metabolic pathway.

Description:

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No Interaction Expected

Irinotecan

Acenocoumarol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Acenocoumarol is mainly metabolised by CYP2C9 and to a lesser extent by CYP1A2 and CYP2C19. Irinotecan does not inhibit or induce CYPs.

Description:

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No Interaction Expected

Irinotecan

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). Irinotecan does not inhibit or induce UGTs.

Description:

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No Interaction Expected

Irinotecan

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%). Irinotecan does not inhibit or induce CYPs.

Description:

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No Interaction Expected

Irinotecan

Alendronic acid

Quality of Evidence: Very Low

Summary:

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

Description:

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No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs.

Description:

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No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs.

Description:

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No Interaction Expected

Irinotecan

Aliskiren

Quality of Evidence: Very Low

Summary:

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

Description:

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No Interaction Expected

Irinotecan

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. Irinotecan does not interact with this metabolic pathway.

Description:

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No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs.

Description:

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No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs.

Description:

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No Interaction Expected

Irinotecan

Aluminium hydroxide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Aluminium hydroxide is not metabolised. Irinotecan is unlikely to interfere with this metabolic pathway.

Description:

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No Interaction Expected

Irinotecan

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 UGTs 1A3, 1A9 and 2B7 and to a lesser extent by CYP3A4 and CYP2C19. Ambrisentan is also a substrate of P-gp. Irinotecan does not inhibit or induce CYPs, UGTs or P-gp.

Description:

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No Interaction Expected

Irinotecan

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. Irinotecan is unlikely to interfere with this elimination pathway.

Description:

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No Interaction Expected

Irinotecan

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. Irinotecan does not interact with this elimination pathway.

Description:

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Potential Weak Interaction

Irinotecan

Amiodarone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Amiodarone is metabolised by CYP3A4 and CYP2C8. Irinotecan does not inhibit or induce CYPs. However, the major metabolite of amiodarone, desethylamiodarone, is an inhibitor of CYPs 3A4 (weak), 2C9 (moderate), 2D6 (moderate), 2C19 (weak), 1A1 (strong) and 2B6 (moderate) and P-gp (strong). Concentrations of irinotecan and SN-38, the active metabolite of irinotecan, may increase due to inhibition of CYP3A4. As the clinical relevance of this interaction is unknown, monitoring for irinotecan toxicity 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

Irinotecan

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 renally eliminated (possibly via OCT). Irinotecan is unlikely to interfere with this elimination pathway.

Description:

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No Interaction Expected

Irinotecan

Amitriptyline

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amitriptyline is metabolised predominantly by CYP2D6 and CYP2C19, with a small proportion metabolised by CYPs 3A4, 1A2 and 2C9. Irinotecan does not inhibit or induce CYPs.

Description:

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No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs.

Description:

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No Interaction Expected

Irinotecan

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. Irinotecan is unlikely to interfere with this elimination pathway.

Description:

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Potential Weak Interaction

Irinotecan

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 but is eliminated to a large extent in the bile. Irinotecan does not interfere with this elimination pathway. However, the European SPC for amphotericin B states that concomitant use of amphotericin B and antineoplastic agents can increase the risk of renal toxicity, bronchospasm and hypotension. Monitoring may be required.

Description:

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No Interaction Expected

Irinotecan

Ampicillin

Quality of Evidence: Very Low

Summary:

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

Description:

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No Interaction Expected

Irinotecan

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. Irinotecan does not interact with this metabolic pathway.

Description:

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No Interaction Expected

Irinotecan

Antacids

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Antacids are not metabolised by CYPs. Irinotecan is unlikely to interfere with this metabolic pathway.

Description:

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No Interaction Expected

Irinotecan

Apixaban

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Apixaban is a substrate of P-gp and BCRP, and is metabolised by CYP3A4 and to a lesser extent by CYPs 1A2, 2C8, 2C9 and 2C19. Irinotecan does not inhibit or induce CYPs, P-gp or BCRP.

Description:

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Potential Weak Interaction

Irinotecan

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. Irinotecan does not inhibit or induce CYPs. However, during treatment aprepitant is a moderate inhibitor of CYP3A4 and may increase concentrations of irinotecan and SN-38, the active metabolite of irinotecan. As the clinical relevance of this interaction is unknown, monitoring for irinotecan toxicity may be required during the few days of coadministration. After treatment, aprepitant is a weak inducer of CYP3A4, CYP2C9 and UGT. Irinotecan and SN-38 concentrations may decrease due to CYP3A4 and UGT1A1 induction. However, this is not considered to be clinically relevant as irinotecan is administered as a single dose.

Description:

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No Interaction Expected

Irinotecan

Aripiprazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Aripiprazole is metabolised by CYP3A4 and CYP2D6. Irinotecan does not inhibit or induce CYPs.

Description:

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No Interaction Expected

Irinotecan

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)). Irinotecan does not inhibit or induce CYPs or UGTs.

Description:

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No Interaction Expected

Irinotecan

Astemizole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Astemizole is metabolised by CYPs 2D6, 2J2 and 3A4. Irinotecan does not inhibit or induce CYPs.

Description:

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No Interaction Expected

Irinotecan

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. Irinotecan is unlikely to interfere with this elimination pathway.

Description:

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No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs, P-gp or OATP1B1.

Description:

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Potential Weak Interaction

Irinotecan

Azathioprine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Azathioprine is converted to 6-mercaptopurine which is metabolised analogously to natural purines. Irinotecan does not interact with this metabolic pathway. However, due to the risk of additive haematological toxicity, haematological parameters should be monitored if coadministered.

Description:

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No Interaction Expected

Irinotecan

Azithromycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Azithromycin is mainly eliminated via biliary excretion; animal data suggest this may occur via P-gp and MRP2. Azithromycin is also an inhibitor of P-gp. Irinotecan is unlikely to interfere with this pathway.

Description:

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No Interaction Expected

Irinotecan

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. Irinotecan does not interact with this metabolic pathway.

Description:

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No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs.

Description:

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No Interaction Expected

Irinotecan

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. Irinotecan does not interact with this pathway.

Description:

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No Interaction Expected

Irinotecan

Bepridil

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bepridil is metabolised by CYP2D6 (major) and CYP3A4. Irinotecan does not inhibit or induce CYPs.

Description:

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No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs.

Description:

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No Interaction Expected

Irinotecan

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. Irinotecan does not interact with this pathway.

Description:

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No Interaction Expected

Irinotecan

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. Irinotecan does not interact with this metabolic or elimination pathway.

Description:

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No Interaction Expected

Irinotecan

Bisoprolol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bisoprolol is partly metabolised by CYP3A4 and CYP2D6, and partly eliminated unchanged in the urine. Irinotecan does not interact with this metabolic or elimination pathway.

Description:

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Potential Weak Interaction

Irinotecan

Bosentan

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Bosentan is a substrate of CYP3A4 and CYP2C9. Irinotecan does not inhibit or induce CYPs. However, bosentan is a weak inducer of CYP3A4 and CYP2C9. Concentrations of irinotecan and SN-38, the active metabolite of irinotecan, may increase due to inhibition of CYP3A4. As the clinical relevance of this interaction is unknown, monitoring for irinotecan toxicity may be required.

Description:

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No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs.

Description:

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No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs.

Description:

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No Interaction Expected

Irinotecan

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). Irinotecan does not inhibit or induce CYPs or UGTs.

Description:

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No Interaction Expected

Irinotecan

Bupropion

Quality of Evidence: Very Low

Summary:

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

Description:

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No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs.

Description:

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No Interaction Expected

Irinotecan

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. Irinotecan is unlikely to interfere with these elimination pathways.

Description:

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No Interaction Expected

Irinotecan

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. Irinotecan is unlikely to interfere with this elimination pathway.

Description:

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No Interaction Expected

Irinotecan

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. Irinotecan is unlikely to interfere with this elimination pathway.

Description:

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No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce OATs.

Description:

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Do Not Coadminister

Irinotecan

Carbamazepine

Quality of Evidence: Very Low

Summary:

Coadministration is contraindicated. Carbamazepine is primarily metabolized by CYP3A4 and to a lesser extent by CYP2C8. Irinotecan does not inhibit or induce CYPs. However, carbamazepine is an inducer of CYPs 2C8 (strong), 2C9 (strong), 3A4 (strong), 1A2 (weak), 2B6 and UGT1A1. Concentrations of irinotecan and SN-38, the active metabolite of irinotecan, may decrease due to induction of CYP3A4 and UGT1A1. Coadministration with the strong CYP3A4 inducers, phenytoin, phenobarbital and carbamazepine, decreased irinotecan AUC by 36-92%. Therefore, coadministration is contraindicated. Selection of an alternate concomitant medicinal product, with no or minimal potential to induce CYP3A4 is recommended. Increasing the dose of irinotecan when coadministering with strong or moderate CYP3A inducers is unlikely to sufficiently compensate for the loss of exposure.

Description:

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No Interaction Expected

Irinotecan

Carvedilol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Carvedilol undergoes glucuronidation via UGTs 1A1, 2B4 and 2B7, and additional metabolism via CYP2D6 and to a lesser extent by CYP2C9 and CYP1A2. Irinotecan does not inhibit or induce CYPs or UGTs.

Description:

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No Interaction Expected

Irinotecan

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. Irinotecan does not interact with this metabolic pathway.

Description:

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No Interaction Expected

Irinotecan

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 renally eliminated unchanged by glomerular filtration and tubular secretion via OAT1 and MATE1. Irinotecan is unlikely to interfere with this elimination pathway.

Description:

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No Interaction Expected

Irinotecan

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. Irinotecan is unlikely to interfere with this elimination pathway.

Description:

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No Interaction Expected

Irinotecan

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. Irinotecan is unlikely to interfere with this elimination pathway.

Description:

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No Interaction Expected

Irinotecan

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. Irinotecan is unlikely to interfere with this elimination pathway.

Description:

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No Interaction Expected

Irinotecan

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. Irinotecan is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan is unlikely to interfere with this elimination pathway.

Description:

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Potential Weak Interaction

Irinotecan

Celecoxib

Quality of Evidence: Very Low

Summary:

Coadministration has been studied and care should be taken. Celecoxib is primarily metabolised by CYP2C9. Irinotecan does not inhibit or induce CYPs. However, after coadministration of celecoxib with docetaxel and irinotecan, a significant increase in irinotecan clearance was observed. The exposure of SN-38, the active metabolite of irinotecan, decreased by 21%. Therefore, monitoring of irinotecan efficacy should be considered.

Description:

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No Interaction Expected

Irinotecan

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. Irinotecan does not interact with this pathway.

Description:

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Potential Weak Interaction

Irinotecan

Chloramphenicol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Chloramphenicol is predominantly glucuronidated. Irinotecan does not inhibit or induce UGTs. However, in vitro studies have shown that chloramphenicol can inhibit metabolism mediated by CYPs 3A4 (strong), 2C19 (strong) and 2D6 (weak). Concentrations of irinotecan and SN-38, the active metabolite of irinotecan, may increase due to inhibition of CYP3A4. As the clinical relevance of this interaction is unknown, monitoring for irinotecan toxicity may be required. 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

Irinotecan

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. Irinotecan does not interact with this pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

Chlorphenamine

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Irinotecan

Chlorpromazine

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not interact with this elimination pathway.

Description:

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Potential Weak Interaction

Irinotecan

Ciclosporin (Cyclosporine)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Ciclosporin is a substrate of CYP3A4 and P-gp. Irinotecan does not inhibit or induce CYPs or P-gp. However, ciclosporin is an inhibitor of CYP3A4 and OATP1B1. Concentrations of irinotecan and SN-38, the active metabolite of irinotecan, may increase due to inhibition of CYP3A4. Compared to irinotecan monotherapy, coadministration with ciclosporin increased SN-38 exposure by 23%-630%. Coadministration with ciclosporin decreased irinotecan clearance by 39%-64%. If coadministration is unavoidable, monitor closely for irinotecan toxicity. Monitor SN-38 plasma concentrations, if available.

Description:

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No Interaction Expected

Irinotecan

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. Irinotecan is unlikely to interfere with this elimination pathway.

Description:

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Potential Weak Interaction

Irinotecan

Cimetidine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Cimetidine is metabolised by CYP450 enzymes. Irinotecan does not inhibit or induce CYPs. 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. Concentrations of irinotecan and SN-38, the active metabolite of irinotecan, may increase due to inhibition of CYP3A4. As the clinical relevance of this interaction is unknown, monitoring for irinotecan toxicity may be required.

Description:

See Summary

Potential Weak Interaction

Irinotecan

Ciprofloxacin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Ciprofloxacin is primarily eliminated unchanged in the kidneys by glomerular filtration and tubular secretion via OAT3. It is also metabolised and partially cleared through the bile and intestine. Irinotecan is unlikely to interfere with this elimination pathway. However, ciprofloxacin is a weak to moderate inhibitor of CYP3A4 and a strong inhibitor of CYP1A2. Concentrations of irinotecan and SN-38, the active metabolite of irinotecan, may increase due to inhibition of CYP3A4. As the clinical relevance of this interaction is unknown, monitoring for irinotecan toxicity may be required.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

Citalopram

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Citalopram is metabolised by CYPs 2C19 (38%), 2D6 (31%) and 3A4 (31%). Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

Potential Interaction

Irinotecan

Clarithromycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Clarithromycin is metabolised by CYP3A4. Irinotecan does not inhibit or induce CYPs. However, clarithromycin is an inhibitor of CYP3A4 (strong) and P-gp. Concentrations of irinotecan and SN-38, the active metabolite of irinotecan, may increase due to inhibition of CYP3A4. After coadministration with the strong CYP3A4 inhibitor ketoconazole, SN-38 exposure increased by approximately 100%. A similar effect may occur after coadministration with clarithromycin. If coadministration is unavoidable, monitor closely for irinotecan toxicity. A dose reduction of irinotecan should be considered. Monitor SN-38 plasma concentrations, if available.

Description:

See Summary

No Interaction Expected

Irinotecan

Clavulanic acid

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Irinotecan

Clemastine

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

Potential Weak Interaction

Irinotecan

Clindamycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Clindamycin is metabolised by CYP3A4. Irinotecan does not inhibit or induce CYPs. However, in vitro data suggest that clindamycin is a CYP3A4 inhibitor and may increase concentrations of irinotecan and SN-38, the active metabolite of irinotecan. As the clinical relevance of this interaction is unknown, monitoring for irinotecan toxicity may be required.

Description:

See Summary

No Interaction Expected

Irinotecan

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

Irinotecan

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. Irinotecan is unlikely to interfere with this elimination pathway. However, in vitro data suggest that clofazimine is a CYP3A4 inhibitor and may increase concentrations of irinotecan and SN-38, the active metabolite of irinotecan. As the clinical relevance of this interaction is unknown, monitoring for irinotecan toxicity may be required.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce OATs.

Description:

See Summary

No Interaction Expected

Irinotecan

Clomipramine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clomipramine is metabolised by CYPs 3A4, 1A2 and 2C19 to desmethylclomipramine, an active metabolite which has a higher activity than the parent drug. Clomipramine and desmethylclomipramine are both metabolised by CYP2D6. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not interact with this pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

Clopidogrel

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clopidogrel is a prodrug and is converted to its active metabolite mainly through CYP2C19 with CYPs 3A4, 2B6 and 1A2 playing a minor role. Clopidogrel is also an inhibitor of CYP2C8 (strong), CYP2B6 (weak) and of CYP2C9 (in vitro) at high concentrations. The clinical relevance of CYP2C9 inhibition is unknown. Irinotecan does not interact with this pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan is unlikely to interfere with this elimination pathway.

Description:

See Summary

Potential Weak Interaction

Irinotecan

Clozapine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Clozapine is metabolised mainly by CYP1A2 and CYP3A4, and to a lesser extent by CYP2C19 and CYP2D6. Irinotecan does not inhibit or induce CYPs. However, due to the risk of additive haematological toxicity, haematological parameters should be monitored if coadministered.

Description:

See Summary

No Interaction Expected

Irinotecan

Codeine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Codeine is converted via CYP2D6 to morphine, an active metabolite with analgesic and opioid properties. 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. The metabolite morphine is a substrate of P-gp. Irinotecan does not inhibit or induce CYPs, UGTs or P-gp.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs or P-gp.

Description:

See Summary

No Interaction Expected

Irinotecan

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 renally excreted via glomerular filtration. Irinotecan is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not interact with this elimination pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

Desipramine

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

Dexamethasone

Quality of Evidence: Very Low

Summary:

Dexamethasone is a substrate of CYP3A4. Irinotecan does not inhibit or induce CYPs. Dexamethasone has also been described as a weak inducer of CYP3A4 and could possibly decrease irinotecan or SN-38, the active metabolite of irinotecan, plasma concentrations. However, the induction of CYP3A4 by dexamethasone has not yet been established. After coadministration of dexamethasone and irinotecan, no differences in irinotecan pharmacokinetics were observed.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

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

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs or UGTs.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs or UGTs.

Description:

See Summary

No Interaction Expected

Irinotecan

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 renally eliminated via OATP4C1 and P-gp. Irinotecan does not inhibit or induce P-gp or OATP4C1.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs or UGTs.

Description:

See Summary

Potential Weak Interaction

Irinotecan

Diltiazem

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Diltiazem is metabolised by CYP3A4 and CYP2D6. Irinotecan does not inhibit or induce CYPs. However, diltiazem is a moderate inhibitor of CYP3A4 and may increase concentrations of irinotecan and SN-38, the active metabolite of irinotecan. As the clinical relevance of this interaction is unknown, monitoring for irinotecan toxicity may be required.

Description:

See Summary

No Interaction Expected

Irinotecan

Diphenhydramine

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce UGTs.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not interact with this metabolic or elimination pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

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%). Irinotecan does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

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 irinotecan, or to be affected if coadministered with irinotecan.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

Doxepin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Doxepin is metabolised to nordoxepin (a metabolite with comparable pharmacological activity as the parent compound) mainly by CYP2C19. Doxepin and nordoxepin are both metabolised by CYP2D6. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

Duloxetine

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

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). Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs or P-gp.

Description:

See Summary

No Interaction Expected

Irinotecan

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). Irinotecan does not inhibit or induce CYPs or UGTs.

Description:

See Summary

No Interaction Expected

Irinotecan

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 renally eliminated (possibly via OATs). Irinotecan is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

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

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan is unlikely to interfere with this elimination pathway.

Description:

See Summary

Potential Weak Interaction

Irinotecan

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. Irinotecan does not inhibit or induce CYPs or P-gp. However, erythromycin is an inhibitor of CYP3A4 (moderate) and P-gp. Concentrations of irinotecan and SN-38, the active metabolite of irinotecan, may increase due to inhibition of CYP3A4. As the clinical relevance of this interaction is unknown, monitoring for irinotecan toxicity may be required.

Description:

See Summary

No Interaction Expected

Irinotecan

Escitalopram

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Escitalopram is metabolised by CYPs 2C19 (37%), 2D6 (28%) and 3A4 (35%) to form N-desmethylescitalopram. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

Esomeprazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Esomeprazole is metabolised by CYP2C19 and CYP3A4. Esomeprazole is also an inhibitor of CYP2C19. Irinotecan does not interact with this pathway. Coadministration of omeprazole, the racemic mixture with esomeprazole, with a single dose of irinotecan did not result in a significant difference in exposure to irinotecan or its metabolites. In addition, no significant difference was observed in the incidence or severity of irinotecan toxicities.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs or UGTs.

Description:

See Summary

No Interaction Expected

Irinotecan

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%). Irinotecan does not interact with this metabolic or elimination pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

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). Irinotecan does not inhibit or induce CYPs or UGTs.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

Potential Weak Interaction

Irinotecan

Everolimus (Immunosuppressant)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Everolimus is mainly metabolised by CYP3A4 and is a substrate of P-gp. Irinotecan does not inhibit or induce CYPs or P-gp. However, due to the risk of additive haematological toxicity, haematological parameters should be monitored if coadministered.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

Ezetimibe

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ezetimibe is glucuronidated by UGTs 1A1 and 1A3 and to a lesser extent by UGTs 2B15 and 2B7. Irinotecan does not inhibit or induce UGTs.

Description:

See Summary

No Interaction Expected

Irinotecan

Famotidine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Famotidine is excreted via OAT1/OAT3. Irinotecan does not inhibit or induce OATs.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not interact with this pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce P-gp.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

Do Not Coadminister

Irinotecan

Fish oils

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is contraindicated. Fish oil may cause chemotherapy resistance in mice. Therefore, coadministration is contraindicated on the days surrounding the administration of chemotherapy.

Description:

See Summary

No Interaction Expected

Irinotecan

Flecainide

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

Potential Weak Interaction

Irinotecan

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. Irinotecan is unlikely to interfere with this elimination pathway. However, flucloxacillin has been described as a CYP3A4 inducer and may decrease concentrations of irinotecan and SN-38, the active metabolite of irinotecan. As the mechanism and clinical relevance of this interaction is unknown, monitoring of irinotecan efficacy may be required.

Description:

See Summary

Potential Weak Interaction

Irinotecan

Fluconazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fluconazole is cleared primarily by renal excretion. Irinotecan is unlikely to interfere with this elimination pathway. However, fluconazole is an inhibitor of CYPs 3A4 (moderate), 2C9 (moderate) and 2C19 (strong). Concentrations of irinotecan and SN-38, the active metabolite of irinotecan, may increase due to inhibition of CYP3A4. As the clinical relevance of this interaction is unknown, monitoring for irinotecan toxicity may be required.

Description:

See Summary

Potential Weak Interaction

Irinotecan

Flucytosine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Flucytosine is metabolised to 5-fluorouracil (5-FU). 5-FU is further metabolised by dihydropyrimidine dehydrogenase to an inactive metabolite. Irinotecan does not interfere with this elimination pathway. However, 5-FU binds to the enzyme thymidylate synthase resulting in DNA damage. This mechanism occurs in all fast dividing cells including bone marrow cells, resulting in haematological toxicity. Irinotecan also induces haematological toxicity which could be enhanced by the use of flucytosine. Due to the risk of additive haematological toxicity, haematological parameters should be monitored if coadministered.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

Fluoxetine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fluoxetine is mainly metabolised by CYP2D6 and CYP2C9 and to a lesser extent by CYP2C19 and CYP3A4 to form norfluoxetine. Fluoxetine is also a strong inhibitor of CYP2D6 and CYP2C19. Irinotecan does not interact with this pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

Fluphenazine

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

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, but the clinical relevance of CYP2C9 inhibition is unknown. Irinotecan does not interact with this pathway.

Description:

See Summary

Potential Weak Interaction

Irinotecan

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. Irinotecan does not inhibit or induce CYPs. However, fluvoxamine is an inhibitor of CYPs 1A2 (strong), 2C19 (strong), 3A4 (moderate), 2C9 (weak-moderate) and 2D6 (weak). Concentrations of irinotecan and SN-38, the active metabolite of irinotecan, may increase due to inhibition of CYP3A4. As the clinical relevance of this interaction is unknown, monitoring for irinotecan toxicity may be required.

Description:

See Summary

No Interaction Expected

Irinotecan

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 predominantly renally eliminated. Irinotecan is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

Formoterol

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

Potential Weak Interaction

Irinotecan

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. Irinotecan does not interact with this metabolic pathway. Aprepitant is mainly metabolized by CYP3A4 and to a lesser extent by CYP1A2 and CYP2C19. Irinotecan does not inhibit or induce CYPs. However, during treatment aprepitant is a moderate inhibitor of CYP3A4 and may increase concentrations of irinotecan and SN-38, the active metabolite of irinotecan. As the clinical relevance of this interaction is unknown, monitoring for irinotecan toxicity may be required during the few days of coadministration. After treatment, aprepitant is a weak inducer of CYP3A4, CYP2C9 and UGT. Irinotecan and SN-38 concentrations may decrease due to CYP3A4 and UGT1A1 induction. However, this is not considered to be clinically relevant as irinotecan is administered as a single dose.

Description:

See Summary

Do Not Coadminister

Irinotecan

Fosphenytoin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is contraindicated. Fosphenytoin is rapidly converted to the active metabolite phenytoin. Irinotecan does not interact with this metabolic pathway. Phenytoin is mainly metabolized by CYP2C9 and to a lesser extent by CYP2C19. Irinotecan does not inhibit or induce CYPs. However, phenytoin is a potent inducer of CYP3A4, UGT and P-gp. Concentrations of irinotecan and SN-38, the active metabolite of irinotecan, may decrease due to induction of CYP3A4 and UGT1A1. Coadministration with the strong CYP3A4 inducers, phenytoin, phenobarbital and carbamazepine, decreased irinotecan AUC by 36-92%. Furthermore, several case reports describe a decrease in irinotecan and SN-38 exposure after coadministration with phenytoin. Therefore, coadministration is contraindicated. Selection of an alternate concomitant medicinal product, with no or minimal potential to induce CYP3A4 is recommended. Increasing the dose of irinotecan when coadministering with strong or moderate CYP3A inducers is unlikely to sufficiently compensate for the loss of exposure.

Description:

See Summary

No Interaction Expected

Irinotecan

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 renally eliminated unchanged (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. Irinotecan does not interact with this pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not interact with this pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs or P-gp.

Description:

See Summary

Do Not Coadminister

Irinotecan

Grapefruit juice

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is contraindicated. Grapefruit juice is known to inhibit CYP3A4 enzymes and may increase concentrations of irinotecan and SN-38, the active metabolite of irinotecan. After coadministration with the strong CYP3A4 inhibitor, ketoconazole, SN-38 exposure increased by approximately 100%. A similar effect may occur after coadministration with grapefruit juice. Therefore, coadministration is contraindicated.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Catechins (green tea compounds) inhibited the UGT1A1-dependent glucuronidation of SN-38 and CYP3A4-dependent oxidation of irinotecan in human liver microsomes in a concentration-dependent manner. However, the catechin concentration needed to inhibit the formation of the inactive metabolites (10 µM or higher) are unlikely to be found in blood of individuals consuming green tea.

Description:

See Summary

Potential Interaction

Irinotecan

Griseofulvin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Less than 1% of a griseofulvin dose is excreted unchanged via the kidneys. Griseofulvin is also a liver microsomal enzyme inducer and may lower plasma levels, and therefore reduce the efficacy of concomitantly administered medicinal products that are metabolised by CYP3A4, such as irinotecan and SN-38 (the active metabolite of irinotecan). The clinical relevance of this interaction is unknown and coadministration should be approached with caution. If coadministration is unavoidable, closely monitor irinotecan efficacy. Monitor SN-38 plasma concentrations, if available.

Description:

See Summary

No Interaction Expected

Irinotecan

Haloperidol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Haloperidol has a complex metabolism as it undergoes glucuronidation (UGTs 2B7>1A4, 1A9), carbonyl reduction as well as oxidative metabolism (CYP3A4 and CYP2D6). Irinotecan does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not interact with this metabolic pathway.

Description:

See Summary

Potential Weak Interaction

Irinotecan

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. Irinotecan does not interact with this metabolic pathway. However, in vitro studies have suggested that hydralazine is a mixed enzyme inhibitor, which may weakly inhibit CYP3A4 and CYP2D6. Concentrations of irinotecan and SN-38, the active metabolite of irinotecan, may increase due to inhibition of CYP3A4. As the clinical relevance of this interaction is unknown, monitoring for irinotecan toxicity may be required.

Description:

See Summary

No Interaction Expected

Irinotecan

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 but 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. Irinotecan is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

Hydrocodone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Hydrocodone is metabolised by CYP2D6 to hydromorphone and by CYP3A4 to norhydrocodone, both of which have analgesic effects. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

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

Irinotecan

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. Irinotecan does not inhibit or induce UGTs.

Description:

See Summary

Potential Weak Interaction

Irinotecan

Hydroxyurea (Hydroxycarbamide)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Hydroxyurea is metabolised in the liver and cleared via the lungs and kidneys. Irinotecan is unlikely to interfere with this elimination pathway. However, due to the risk of additive haematological toxicity, haematological parameters should be monitored if coadministered.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

Ibandronic acid

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs or UGTs.

Description:

See Summary

No Interaction Expected

Irinotecan

Iloperidone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Iloperidone is metabolised by CYP3A4 and CYP2D6. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan is unlikely to interfere with these elimination pathways.

Description:

See Summary

No Interaction Expected

Irinotecan

Imipramine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Imipramine is metabolised by CYPs 3A4, 2C19 and 1A2 to desipramine. Imipramine and desipramine are both metabolised by CYP2D6. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

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. 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. Irinotecan does not inhibit or induce CYPs or OATs.

Description:

See Summary

No Interaction Expected

Irinotecan

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

Potential Weak Interaction

Irinotecan

Interferon alpha

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. However, due to the risk of additive haematological toxicity, haematological parameters should be monitored if coadministered.

Description:

See Summary

Potential Weak Interaction

Irinotecan

Interleukin 2 (Aldesleukin)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Interleukin-2 is mainly eliminated by glomerular filtration. Irinotecan is unlikely to interfere with this elimination pathway. However, due to the risk of additive haematological toxicity, haematological parameters should be monitored if coadministered.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

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). Irinotecan does not inhibit or induce CYPs or UGTs.

Description:

See Summary

No Interaction Expected

Irinotecan

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

Irinotecan

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. Irinotecan does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

Potential Interaction

Irinotecan

Itraconazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Itraconazole is primarily metabolised by CYP3A4. Irinotecan does not inhibit or induce CYPs. However, itraconazole is an inhibitor of CYP3A4 (strong), CYP2C9 (weak), P-gp and BCRP. Concentrations of irinotecan and SN-38, the active metabolite of irinotecan, may increase due to inhibition of CYP3A4. After coadministration with the strong CYP3A4 inhibitor, ketoconazole, SN-38 exposure increased by approximately 100%. A similar effect may occur after coadministration with itraconazole. If coadministration is unavoidable, monitor closely for irinotecan toxicity. A dose reduction of irinotecan should be considered. Monitor SN-38 plasma concentrations, if available.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan is unlikely to interfere with this elimination pathway.

Description:

See Summary

Potential Interaction

Irinotecan

Ketoconazole

Quality of Evidence: Very Low

Summary:

Coadministration should be approached with caution. Ketoconazole is a substrate of CYP3A4. Irinotecan does not inhibit or induce CYPs. However, ketoconazole is an inhibitor of CYP3A4 (strong) and P-gp. Concentrations of irinotecan and SN-38, the active metabolite of irinotecan may increase due to inhibition of CYP3A4. After coadministration with ketoconazole, SN-38 exposure increased by approximately 100%. If coadministration is unavoidable, monitor closely for irinotecan toxicity. A dose reduction of irinotecan should be considered. Monitor SN-38 plasma concentrations, if available.

Description:

See Summary

No Interaction Expected

Irinotecan

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). Irinotecan does not inhibit or induce UGTs.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

Lansoprazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lansoprazole is mainly metabolised by CYP2C19 and to a lesser extent by CYP3A4. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

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

Description:

See Summary

No Interaction Expected

Irinotecan

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

Description:

See Summary

No Interaction Expected

Irinotecan

Levomepromazine

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs or UGTs.

Description:

See Summary

No Interaction Expected

Irinotecan

Levonorgestrel (Emergency Contraception)

Quality of Evidence: Very Low

Summary:

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

Potential Weak Interaction

Irinotecan

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. Irinotecan does not inhibit or induce CYPs or P-gp. However, linagliptin is a weak inhibitor of CYP3A4 and may increase concentrations of irinotecan and SN-38, the active metabolite of irinotecan. As the clinical relevance of this interaction is unknown, monitoring for irinotecan toxicity may be required.

Description:

See Summary

No Interaction Expected

Irinotecan

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

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

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 renally eliminated unchanged via glomerular filtration. Irinotecan is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

Lithium

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

Do Not Coadminister

Irinotecan

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. If coadministration is judged clinically necessary, use with extreme caution since generalised infections can occur.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs or P-gp.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

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

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce UGTs.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

Maprotiline

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

Medroxyprogesterone (non-depot)

Quality of Evidence: Very Low

Summary:

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs or UGTs.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not interact with this metabolic pathway.

Description:

See Summary

Potential Interaction

Irinotecan

Metamizole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. 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%). Irinotecan does not interact with this metabolic pathway. However, metamizole is an inducer of CYP3A4. Concentrations of irinotecan and SN-38, the active metabolite of irinotecan, may decrease due to induction of CYP3A4. The clinical relevance of this interaction is unknown, Therefore, coadministration should be approached with caution. If coadministration is unavoidable, closely monitor irinotecan efficacy. Monitor SN-38 plasma concentrations, if available.

Description:

See Summary

No Interaction Expected

Irinotecan

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 OCT1/2/3, MATE1 and MATE2K. Irinotecan does not inhibit or induce OCTs or MATEs.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

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 methylphenidate to affect disposition of irinotecan, or to be affected if coadministered with irinotecan.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

Metoclopramide

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

Metoprolol

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Irinotecan

Metronidazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metronidazole is eliminated via glomerular filtration. Irinotecan 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). Although irinotecan and SN-38, the active metabolite of irinotecan, are substrates of CYP3A4, no clinically relevant effect on irinotecan exposure is expected.

Description:

See Summary

No Interaction Expected

Irinotecan

Mexiletine

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Irinotecan

Mianserin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Mianserin is metabolised by CYP2D6 and CYP1A2, and to a lesser extent by CYP3A4. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

Potential Interaction

Irinotecan

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. Irinotecan is unlikely to interfere with this unspecified metabolic pathway. However, miconazole is an inhibitor of CYP2C9 (moderate) and CYP3A4 (strong). Concentrations of irinotecan and SN-38, the active metabolite of irinotecan, may increase due to inhibition of CYP3A4. After coadministration with the strong CYP3A4 inhibitor, ketoconazole, SN-38 exposure was increased by approximately 100%. A similar effect may occur after coadministration with miconazole. If coadministration is unavoidable, monitor closely for irinotecan toxicity. A dose reduction of irinotecan should be considered. Monitor SN-38 plasma concentrations, if available. Note: after dermal application miconazole is only minimally absorbed. Therefore, no clinical relevant interaction is expected.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

Midazolam (parenteral)

Quality of Evidence: Very Low

Summary:

Description:

See Summary

No Interaction Expected

Irinotecan

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

Description:

See Summary

No Interaction Expected

Irinotecan

Mirtazapine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Mirtazapine is metabolised to 8-hydroxymirtazapine by CYP2D6 and CYP1A2, and to N-desmethylmirtazapine mainly by CYP3A4. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

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 CYP3A4 and CYP2C9. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce UGTs or P-gp.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce UGTs.

Description:

See Summary

Potential Weak Interaction

Irinotecan

Mycophenolate

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Mycophenolate is mainly glucuronidated by UGT1A9 and UGT2B7. The active metabolite of mycophenolate, mycophenolic acid, is an inhibitor of OAT1/OAT3. Irinotecan does not interact with this metabolic pathway. However, due to the risk of additive haematological toxicity, haematological parameters should be monitored if coadministered.

Description:

See Summary

No Interaction Expected

Irinotecan

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 renally excreted by a nonsaturable mechanism. Irinotecan is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs or UGTs.

Description:

See Summary

No Interaction Expected

Irinotecan

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%). Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

Nebivolol

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

Potential Interaction

Irinotecan

Nefazodone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Nefazodone is metabolised mainly by CYP3A4. Irinotecan does not inhibit or induce CYPs. However, nefazodone is a strong inhibitor of CYP3A4 and may increase concentrations of irinotecan and SN-38, the active metabolite of irinotecan. After coadministration with the strong CYP3A4 inhibitor, ketoconazole, SN-38 exposure increased by approximately 100%. A similar effect may occur after coadministration with nefazodone. If coadministration is unavoidable, monitor closely for irinotecan toxicity. A dose reduction of irinotecan should be considered. Monitor SN-38 plasma concentrations, if available.

Description:

See Summary

Potential Weak Interaction

Irinotecan

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. Irinotecan does not inhibit or induce CYPs. However, nicardipine is a weak inhibitor of CYP3A4 and may increase concentrations of irinotecan and SN-38, the active metabolite of irinotecan. As the clinical relevance of this interaction is unknown, monitoring for irinotecan toxicity may be required.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

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%). Irinotecan does not interact with this metabolic or elimination pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

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). Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs or UGTs.

Description:

See Summary

No Interaction Expected

Irinotecan

Nortriptyline

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Irinotecan

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

Irinotecan

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. Irinotecan is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

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). Irinotecan does not inhibit or induce CYPs or UGTs.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

Omeprazole

Quality of Evidence: Very Low

Summary:

Coadministration has been studied and based on metabolism and clearance a clinically significant interaction is unlikely. 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. Irinotecan does not interact with this pathway. Coadministration of omeprazole with a single dose of irinotecan did not result in a significant difference in exposure to irinotecan or its metabolites. In addition, no significant difference was observed in the incidence or severity of irinotecan toxicities.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Ondansetron is also a substrate of P-gp. Irinotecan does not inhibit or induce CYPs or P-gp.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce UGTs.

Description:

See Summary

Potential Interaction

Irinotecan

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 cystolic enzymes. Irinotecan does not interact with this metabolic pathway. However, both oxcarbazepine and MHD are inducers of CYP3A4 (moderate) and CYP3A5 and are inhibitors of CYP2C19. Concentrations of irinotecan and SN-38, the active metabolite of irinotecan, may decrease due to induction of CYP3A4. The clinical relevance of this interaction is unknown. Therefore, coadministration should be approached with caution. If coadministration is unavoidable, closely monitor irinotecan efficacy. Monitor SN-38 plasma concentrations, if available.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce UGTs.

Description:

See Summary

No Interaction Expected

Irinotecan

Oxycodone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Oxycodone is metabolised principally to noroxycodone via CYP3A and oxymorphone via CYP2D6. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

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 renally eliminated (possibly via OCT) with minimal metabolism occurring via CYP2D6 and CYP3A4. Irinotecan does not interact with this metabolic or elimination pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Palonosetron is also a substrate of P-gp. Irinotecan does not inhibit or induce CYPs or P-gp.

Description:

See Summary

No Interaction Expected

Irinotecan

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 but is cleared from the plasma by uptake into bone and elimination via renal excretion. Irinotecan is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

Pantoprazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pantoprazole is mainly metabolised by CYP2C19 and to a lesser extent by CYPs 3A4, 2D6 and 2C9. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

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), sulfation and to a lesser extent, by oxidation (CYPs 2E1 (major), 1A2, 3A4 and 2D6). Irinotecan does not inhibit or induce CYPs or UGTs.

Description:

See Summary

No Interaction Expected

Irinotecan

Paroxetine

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

Potential Weak Interaction

Irinotecan

Peginterferon alfa-2a

Quality of Evidence: Very Low

Summary:

Description:

See Summary

No Interaction Expected

Irinotecan

Penicillins

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs or FMO3.

Description:

See Summary

No Interaction Expected

Irinotecan

Periciazine

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

Perphenazine

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not interact with this metabolic pathway.

Description:

See Summary

Do Not Coadminister

Irinotecan

Phenobarbital (Phenobarbitone)

Quality of Evidence: Very Low

Summary:

Coadministration is contraindicated. Phenobarbital is metabolized by CYP2C19 and CYP2C9 (major) and to a lesser extent by CYP2E1. Irinotecan does not inhibit or induce CYPs. However, phenobarbital is a strong inducer of CYPs 3A4, 2C9, 2C8 and UGTs. Concentrations of irinotecan and SN-38, the active metabolite of irinotecan, may decrease due to induction of CYP3A4 and UGT1A1. Coadministration with phenobarbital decreased irinotecan AUC by 27% and SN-38 AUC by 75%. The SN-38/irinotecan AUC ratio decreased by 64%. Therefore, coadministration is contraindicated. Selection of an alternate concomitant medicinal product, with no or minimal potential to induce CYP3A4 is recommended. Increasing the dose of irinotecan when coadministering with strong or moderate CYP3A inducers is unlikely to sufficiently compensate for the loss of exposure.

Description:

See Summary

No Interaction Expected

Irinotecan

Phenprocoumon

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Phenprocoumon is mainly metabolised by CYP2C9 and CYP3A4. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

Do Not Coadminister

Irinotecan

Phenytoin

Quality of Evidence: Very Low

Summary:

Coadministration is contraindicated. Phenytoin is mainly metabolized by CYP2C9 and to a lesser extent by CYP2C19. Irinotecan does not inhibit or induce CYPs. However, phenytoin is a potent inducer of CYP3A4, UGT and P-gp. Concentrations of irinotecan and SN-38, the active metabolite of irinotecan, may decrease due to induction of CYP3A4 and UGT1A1. Coadministration with the strong CYP3A4 inducers, phenytoin, phenobarbital and carbamazepine, decreased irinotecan AUC by 36-92%. Furthermore, several case reports describe a decrease in irinotecan and SN-38 exposure after coadministration with phenytoin. Therefore, coadministration is contraindicated. Selection of an alternate concomitant medicinal product, with no or minimal potential to induce CYP3A4 is recommended. Increasing the dose of irinotecan when coadministering with strong or moderate CYP3A inducers is unlikely to sufficiently compensate for the loss of exposure.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

Pimozide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pimozide is mainly metabolised by CYP3A4 and CYP2D6 and to a lesser extent by CYP1A2. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

Pindolol

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

Pipotiazine

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

Pitavastatin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pitavastatin is metabolised by UGTs 1A3 and 2B7 with minimal metabolism by CYPs 2C9 and 2C8. Pitavastatin is also a substrate of OATP1B1. Irinotecan does not inhibit or induce CYPs, UGTs or OATP1B1.

Description:

See Summary

Potential Interaction

Irinotecan

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. Irinotecan does not inhibit or induce UGTs or P-gp. However, posaconazole is a strong inhibitor of CYP3A4 and may increase concentrations of irinotecan and SN-38, the active metabolite of irinotecan. After coadministration with the strong CYP3A4 inhibitor, ketoconazole, SN-38 exposure increased by approximately 100%. A similar effect may occur after coadministration with posaconazole. If coadministration is unavoidable, monitor closely for irinotecan toxicity. A dose reduction of irinotecan should be considered. Monitor SN-38 plasma concentrations, if available.

Description:

See Summary

No Interaction Expected

Irinotecan

Potassium

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs or OATP1B1.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

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

Description:

See Summary

No Interaction Expected

Irinotecan

Prochlorperazine

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Irinotecan

Promethazine

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Irinotecan

Propafenone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Propafenone is metabolised mainly by CYP2D6 and to a lesser extent by CYP1A2 and CYP3A4. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

Propranolol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Propranolol is metabolised by 3 routes (aromatic hydroxylation by CYP2D6, N-dealkylation followed by side chain hydroxylation via CYPs 1A2, 2C19, 2D6, and direct glucuronidation). Irinotecan does not inhibit or induce CYPs or UGTs.

Description:

See Summary

No Interaction Expected

Irinotecan

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 renally eliminated, partly by active secretion by renal transporters. Prucalopride is also a substrate of P-gp. Irinotecan does not interact with this elimination pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

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

Irinotecan

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. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not interact with this metabolic or elimination pathway.

Description:

See Summary

Potential Weak Interaction

Irinotecan

Quinidine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Quinidine is mainly metabolised by CYP3A4 and to a lesser extent by CYP2C9 and CYP2E1. Quinidine is also a substrate of P-gp. Irinotecan does not inhibit or induce CYPs or P-gp. However, quinidine is an inhibitor of CYP2D6 (strong), CYP3A4 (weak) and P-gp (moderate). Concentrations of irinotecan and SN-38, the active metabolite of irinotecan, may increase due to inhibition of CYP3A4. As the clinical relevance of this interaction is unknown, monitoring for irinotecan toxicity may be required.

Description:

See Summary

No Interaction Expected

Irinotecan

Rabeprazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Rabeprazole is mainly metabolised via non-enzymatic reduction and to a lesser extent by CYP2C19 and CYP3A4. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

Ranitidine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ranitidine is excreted via OAT1/OAT3. Irinotecan does not inhibit or induce OATs.

Description:

See Summary

Potential Weak Interaction

Irinotecan

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. Irinotecan does not inhibit or induce CYPs or P-gp. However, ranolazine is a weak inhibitor of P-gp, CYP3A4 and CYP2D6. Concentrations of irinotecan and SN-38, the active metabolite of irinotecan, may increase due to inhibition of CYP3A4. As the clinical relevance of this interaction is unknown, monitoring for irinotecan toxicity may be required.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs. In vitro data indicate reboxetine to be a weak inhibitor of CYP3A4 but in vivo data showed no inhibitory effect on CYP3A4. Although irinotecan and SN-38, the active metabolite of irinotecan, are substrates of CYP3A4, no clinically relevant effect on reboxetine exposure is expected.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs or OATP1B1.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

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

Irinotecan

Rifabutin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is contraindicated. Rifabutin is metabolised by CYP3A4 and via deacetylation. Irinotecan does not interact with this metabolic pathway. However, rifabutin is a strong CYP3A4 and P-gp inducer. Concentrations of irinotecan and SN-38, the active metabolite of irinotecan, may decrease due to induction of CYP3A4. Coadministration with the strong CYP3A4 inducers, phenytoin, phenobarbital and carbamazepine, decreased irinotecan AUC by 36-92%. A similar effect may occur after coadministration with rifabutin. Therefore, coadministration is contraindicated. Selection of an alternate concomitant medicinal product, with no or minimal potential to induce CYP3A4 is recommended. Increasing the dose of irinotecan when coadministering with strong or moderate CYP3A inducers is unlikely to sufficiently compensate for the loss of exposure.

Description:

See Summary

Do Not Coadminister

Irinotecan

Rifampicin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is contraindicated. Rifampicin is metabolised via deacetylation. Irinotecan does not interact with this metabolic pathway. However, rifampicin is a strong CYP3A4 and P-gp inducer. Concentrations of irinotecan and SN-38, the active metabolite of irinotecan, may decrease due to induction of CYP3A4. Coadministration with the strong CYP3A4 inducers, phenytoin, phenobarbital and carbamazepine, decreased irinotecan AUC by 36-92%. A similar effect may occur after coadministration with rifampicin. Therefore, coadministration is contraindicated. Selection of an alternate concomitant medicinal product, with no or minimal potential to induce CYP3A4 is recommended. Increasing the dose of irinotecan when coadministering with strong or moderate CYP3A inducers is unlikely to sufficiently compensate for the loss of exposure.

Description:

See Summary

Do Not Coadminister

Irinotecan

Rifapentine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is contraindicated. Rifapentine is metabolised via deacetylation. Irinotecan does not interact with this metabolic pathway. However, rifapentine is a strong CYP3A4, CYP2C8 and P-gp inducer. Concentrations of irinotecan and SN-38, the active metabolite of irinotecan, may decrease due to induction of CYP3A4. Coadministration with the strong CYP3A4 inducers, phenytoin, phenobarbital and carbamazepine, decreased irinotecan AUC by 36-92%. A similar effect may occur after coadministration with rifapentine. Therefore, coadministration is contraindicated. Selection of an alternate concomitant medicinal product, with no or minimal potential to induce CYP3A4 is recommended. Increasing the dose of irinotecan when coadministering with strong or moderate CYP3A inducers is unlikely to sufficiently compensate for the loss of exposure.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

Risperidone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Risperidone is metabolised by CYP2D6 and to a lesser extent by CYP3A4. Risperidone is also a substrate of P-gp. Irinotecan does not inhibit or induce CYPs or P-gp.

Description:

See Summary

No Interaction Expected

Irinotecan

Rivaroxaban

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant is unlikely. Rivaroxaban is partly metabolised in the liver (by CYP3A4, CYP2J2 and hydrolytic enzymes) and partly eliminated unchanged in urine. Rivaroxaban is also a substrate of P-gp and BCRP. Irinotecan does not interact with this metabolic or elimination pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

Rosuvastatin

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

Salmeterol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Salmeterol is metabolised by CYP3A4. The systemic exposure of salmeterol is low and irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs or P-gp.

Description:

See Summary

No Interaction Expected

Irinotecan

Senna

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Irinotecan

Sertindole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Sertindole is metabolised by CYP2D6 and CYP3A4. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

Simvastatin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Simvastatin is metabolised by CYP3A4. Simvastatin is also a substrate of BCRP and the active metabolite is a substrate of OATP1B1. Irinotecan does not inhibit or induce CYPs, BCRP or OATP1B1.

Description:

See Summary

Potential Weak Interaction

Irinotecan

Sirolimus

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Sirolimus is metabolised by CYP3A4 and is a substrate of P-gp. Irinotecan does not inhibit or induce CYPs or P-gp. However, due to the risk of additive haematological toxicity, haematological parameters should be monitored if coadministered.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not interact with this metabolic or elimination pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

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

Description:

See Summary

Do Not Coadminister

Irinotecan

St John's Wort

Quality of Evidence: Very Low

Summary:

Coadministration is contraindicated. St John’s wort is a P-gp and CYP3A4 inducer. Concentrations of irinotecan and SN-38, the active metabolite of irinotecan, may decrease due to CYP3A4 induction. After coadministration with St John’s Wort, SN-38 exposure decreased by 42%. Therefore, coadministration is contraindicated.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan is unlikely to interfere with this elimination pathway.

Description:

See Summary

Potential Weak Interaction

Irinotecan

Tacrolimus

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Tacrolimus is metabolised mainly by CYP3A4. Irinotecan does not inhibit or induce CYPs. Tacrolimus is an inhibitor of CYP3A4 and OATP1B1 in vitro but produced modest inhibition of CYP3A4 and OATP1B1 in the range of clinical concentrations. Although irinotecan and SN-38, the active metabolite of irinotecan, are substrates of CYP3A4, no clinically relevant effect on irinotecan or SN-38 exposure is expected. However, due to the risk of additive haematological toxicity, haematological parameters should be monitored if coadministered.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

Tazobactam

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

Potential Interaction

Irinotecan

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. Irinotecan does not interact with this metabolic pathway. However, telithromycin is an inhibitor of CYP3A4 (strong) and P-gp, but the clinical relevance of P-gp inhibition is unknown. Concentrations of irinotecan and SN-38, the active metabolite of irinotecan, may increase due to inhibition of CYP3A4. After coadministration with the strong CYP3A4 inhibitor, ketoconazole, SN-38 exposure increased by approximately 100%. A similar effect may occur after coadministration with telithromycin. If coadministration is unavoidable, monitor closely for irinotecan toxicity. A dose reduction of irinotecan should be considered. Monitor SN-38 plasma concentrations, if available.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce UGTs.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce UGTs.

Description:

See Summary

No Interaction Expected

Irinotecan

Terbinafine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Terbinafine is metabolised by CYPs 1A2, 2C9, 3A4 and to a lesser extent by CYP2C8 and CYP2C19. Terbinafine is also a moderate-strong inhibitor of CYP2D6. Irinotecan does not interact with this pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

Thiamine (Vitamin B1)

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Irinotecan

Thioridazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Thioridazine is metabolised by CYP2D6 and to a lesser extent by CYP3A4. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan is unlikely to interfere with this elimination pathway.

Description:

See Summary

Potential Weak Interaction

Irinotecan

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. Irinotecan does not inhibit or induce CYPs or P-gp. However, ticagrelor is a mild inhibitor of CYP3A4 and may increase concentrations of irinotecan and SN-38, the active metabolite of irinotecan. As the clinical relevance of this interaction is unknown, monitoring for irinotecan toxicity may be required.

Description:

See Summary

No Interaction Expected

Irinotecan

Timolol

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

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 CYP2C8 and CYP2C19. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

Tolterodine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tolterodine is primarily metabolised by CYP2D6 with CYP3A4 playing a minor role. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

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. 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. Irinotecan does not inhibit or induce CYPs or OATs.

Description:

See Summary

No Interaction Expected

Irinotecan

Tramadol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tramadol is metabolised by CYPs 3A4, 2B6, and 2D6. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not interact with these pathways.

Description:

See Summary

No Interaction Expected

Irinotecan

Trimipramine

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Irinotecan

Tropisetron

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not interact with this pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

Venlafaxine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Venlafaxine is mainly metabolised by CYP2D6 and to a lesser extent by CYPs 3A4, 2C19 and 2C9. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

Potential Weak Interaction

Irinotecan

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. Irinotecan does not inhibit or induce CYPs. However, verapamil is a moderate inhibitor of CYP3A4 and may increase concentrations of irinotecan and SN-38, the active metabolite of irinotecan. As the clinical relevance of this interaction is unknown, monitoring for irinotecan toxicity may be required.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

Vitamin E

Quality of Evidence: Very Low

Summary:

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

Description:

See Summary

Potential Interaction

Irinotecan

Voriconazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Voriconazole is metabolised by CYP2C19 (major) and to a lesser extent by CYP3A4 and CYP2C9. Irinotecan does not inhibit or induce CYPs. However, voriconazole is a strong inhibitor of CYP3A4 and a weak inhibitor of CYPs 2C9, 2C19 and 2B6. Concentrations of irinotecan and SN-38, the active metabolite of irinotecan, may increase due to inhibition of CYP3A4. After coadministration with the strong CYP3A4 inhibitor, ketoconazole, SN-38 exposure increased by approximately 100%. A similar effect may occur after coadministration with voriconazole. If coadministration is unavoidable, monitor closely for irinotecan toxicity. A dose reduction of irinotecan should be considered. Monitor SN-38 plasma concentrations, if available.

Description:

See Summary

No Interaction Expected

Irinotecan

Warfarin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. 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. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

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 by P3A4. Irinotecan does not interact with this metabolic pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

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). Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

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 but is cleared from the plasma by uptake into bone and elimination via renal excretion. Irinotecan is unlikely to interfere with this elimination pathway.

Description:

See Summary

No Interaction Expected

Irinotecan

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 CYPs 2C9, 2C19, 2D6 and 1A2. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

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. Irinotecan does not inhibit or induce CYPs.

Description:

See Summary

No Interaction Expected

Irinotecan

Zuclopenthixol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Zuclopenthixol is metabolised by sulphoxidation, N-dealkylation (via CYP2D6 and CYP3A4) and glucuronidation. Irinotecan does not inhibit or induce CYPs or UGTs.

Description:

See Summary