Cancer Drug Interactions from Radboud UMC and University of Liverpool

No Interaction Expected

Alectinib

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. Alectinib does not interact with this metabolic pathway.

Description:

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No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs

Description:

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No Interaction Expected

Alectinib

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). Alectinib does not inhibit or induce UGTs

Description:

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No Interaction Expected

Alectinib

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%). Alectinib does not inhibit or induce CYPs.

Description:

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No Interaction Expected

Alectinib

Alendronic acid

Quality of Evidence: Very Low

Summary:

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

Description:

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No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

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No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

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Potential Weak Interaction

Alectinib

Aliskiren

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Aliskiren is minimally metabolised and is mainly excreted unchanged in faeces. Alectinib is unlikely to interfere with this elimination pathway. Aliskiren is also a substrate of P-gp and concentrations may increase due to inhibition by alectinib and its active metabolite M4. Monitoring for aliskiren toxicity should be considered.

Description:

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No Interaction Expected

Alectinib

Allopurinol

Quality of Evidence: Very Low

Summary:

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

Description:

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No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs. Combined exposure of alectinib and its active metabolite M4 increased by only 17% after coadministration with the proton-pump inhibitor esomeprazole. A similar effect may occur after coadministration with alosetron. Therefore, no clinically relevant effect on alectinib and M4 combined exposure is expected due to pH elevation caused by alosetron.

Description:

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No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

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No Interaction Expected

Alectinib

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. Combined exposure of alectinib and its active metabolite M4 increased by only 17% after coadministration with the proton-pump inhibitor esomeprazole. A similar effect may occur after coadministration with aluminium hydroxide. Therefore, no clinically relevant effect on alectinib and M4 combined exposure is expected due to pH elevation caused by aluminium hydroxide.

Description:

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Potential Weak Interaction

Alectinib

Ambrisentan

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Ambrisentan is metabolized by glucuronidation via UGT1A3, UGT1A9 and UGT2B7 and to a lesser extent by CYP3A4 and CYP2C19. Alectinib does not inhibit or induce UGTs or CYPs. Ambrisentan is also a substrate of P-gp and concentrations may increase due to inhibition by alectinib and its active metabolite M4. Monitoring for ambrisentan toxicity should be considered.

Description:

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No Interaction Expected

Alectinib

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. Alectinib is unlikely to interfere with this elimination pathway.

Description:

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No Interaction Expected

Alectinib

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

Description:

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No Interaction Expected

Alectinib

Amiodarone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amiodarone is metabolised by CYP3A4 and CYP2C8. Moreover, the major metabolite of amiodarone, desethylamiodarone, is an inhibitor of CYP3A4 (weak), CYP2C9 (moderate), CYP2D6 (moderate), CYP2C19 (weak), CYP1A1 (strong), CYP2B6 (moderate) and P-gp (strong). Alectinib does not interact with this metabolic pathway.

Description:

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No Interaction Expected

Alectinib

Amisulpride

Quality of Evidence: Very Low

Summary:

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

Description:

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No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

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No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

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No Interaction Expected

Alectinib

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

Description:

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Potential Weak Interaction

Alectinib

Amphotericin B

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Amphotericin B is not appreciably metabolised and is eliminated to a large extent in the bile. Alectinib is unlikely to interfere with this elimination pathway. However, the European SPC for amphotericin states that concomitant use of amphotericin B and antineoplastic agents can increase the risk of renal toxicity, bronchospasm and hypotension and so monitoring may be required.

Description:

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No Interaction Expected

Alectinib

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. Alectinib Is unlikely to interfere with this elimination pathway.

Description:

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No Interaction Expected

Alectinib

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. Alectinib does not interact with this metabolic pathway.

Description:

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No Interaction Expected

Alectinib

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. Combined exposure of alectinib and its active metabolite M4 increased by only 17% after coadministration with the proton-pump inhibitor esomeprazole. A similar effect may occur after coadministration with antacids. Therefore, no clinically relevant effect on alectinib and M4 combined exposure is expected due to pH elevation caused by antacids.

Description:

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Potential Interaction

Alectinib

Apixaban

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Apixaban is metabolised by CYP3A4 and to a lesser extent by CYPs 1A2, 2C8, 2C9 and 2C19. Alectinib does not inhibit or induce CYPs. However, apixaban is a substrate of P-gp and BCRP and concentrations may increase due to inhibition of both P-gp and BCRP by alectinib and its active metabolite M4. If coadministration cannot be avoided, reduce the apixaban dose by 25%. Monitor closely for apixaban toxicity and anti-Xa levels.

Description:

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No Interaction Expected

Alectinib

Aprepitant

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Aprepitant is mainly metabolized by CYP3A4 and to a lesser extent by CYP1A2 and CYP2C19. Alectinib does not inhibit or induce CYPs. During treatment aprepitant is a moderate inhibitor of CYP3A4. Exposure to alectinib and its active metabolite M4 may increase due to inhibition of CYP3A4 by aprepitant, but this is unlikely to be clinically significant. After treatment aprepitant is a weak inducer of CYP3A4, CYP2C9 and UGT. Alectinib is metabolised by CYP3A4 to its active metabolite M4 and combined exposure may alter due to induction by aprepitant. However, after coadministration with rifampicin, a strong CYP3A4 inducer, combined exposure of alectinib and M4 reduced by only 18%. Therefore, a clinically relevant effect on combined exposure of alectinib and M4 due to CYP3A4 induction by aprepitant is not expected.

Description:

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No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

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No Interaction Expected

Alectinib

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

Description:

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No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

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No Interaction Expected

Alectinib

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. Alectinib is unlikely to interfere with this elimination pathway.

Description:

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Potential Weak Interaction

Alectinib

Atorvastatin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Atorvastatin is metabolised by CYP3A4. Alectinib does not inhibit or induce CYPs. Atorvastatin is also a substrate of OATP1B1 and P-gp and concentrations may increase due to P-gp inhibition by alectinib and its active metabolite M4. Monitoring for atorvastatin toxicity should be considered.

Description:

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No Interaction Expected

Alectinib

Azathioprine

Quality of Evidence: Very Low

Summary:

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

Description:

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Potential Weak Interaction

Alectinib

Azithromycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Azithromycin is mainly eliminated via biliary excretion; animal data suggest this may occur via MRP2 and P-gp. Concentrations may increase due to P-gp inhibition by alectinib and its active metabolite M4. Therefore, monitoring for azithromycin toxicity should be considered. Azithromycin is also an inhibitor of P-gp. The clinical relevance of P-gp inhibition by azithromycin is unknown. M4 is an in vitro substrate of P-gp and concentrations may increase due to inhibition by azithromycin. However, as alectinib inhibits P-gp, it is not expected that coadministration with azithromycin will have a clinically relevant effect on M4 exposure.

Description:

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No Interaction Expected

Alectinib

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. Alectinib does not interact with this metabolic pathway.

Description:

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No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

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No Interaction Expected

Alectinib

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

Description:

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No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

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No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

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No Interaction Expected

Alectinib

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. Alectinib is unlikely to interfere with this elimination pathway.

Description:

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No Interaction Expected

Alectinib

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

Description:

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No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs and is unlikely to interfere with this elimination pathway.

Description:

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No Interaction Expected

Alectinib

Bosentan

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bosentan is a substrate and weak inducer of CYP3A4 and CYP2C9. Alectinib does not inhibit or induce CYPs. Alectinib is metabolised by CYP3A4 to its active metabolite M4 and combined exposure may alter due to induction by bosentan. However, after coadministration with rifampicin, a strong CYP3A4 inducer, combined exposure of alectinib and M4 reduced by only 18%. Therefore, a clinically relevant effect on combined exposure of alectinib and M4 due to CYP3A4 induction by bosentan is not expected.

Description:

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No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

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No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

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No Interaction Expected

Alectinib

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

Description:

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No Interaction Expected

Alectinib

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. Alectinib does not interact with this metabolic pathway.

Description:

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No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

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No Interaction Expected

Alectinib

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. Alectinib is unlikely to interfere with this elimination pathway.

Description:

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No Interaction Expected

Alectinib

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. Alectinib is unlikely to interfere with this elimination pathway.

Description:

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No Interaction Expected

Alectinib

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. Alectinib is unlikely to interfere with this elimination pathway.

Description:

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No Interaction Expected

Alectinib

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

Description:

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No Interaction Expected

Alectinib

Carbamazepine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Carbamazepine is primarily metabolized by CYP3A4 and to a lesser extent by CYP2C8. Alectinib does not inhibit or induce CYPs. Carbamazepine is also an inducer of CYP2C8 (strong), CYP2C9 (strong), CYP3A4 (strong), CYP1A2 (weak), CYP2B6, UGT1A1 and P-gp (moderate). Alectinib is metabolised by CYP3A4 to its active metabolite M4 and combined exposure may alter due to induction by carbamazepine. However, after coadministration with rifampicin, a strong CYP3A4 inducer, combined exposure of alectinib and M4 reduced by only 18%. Therefore, a clinically relevant effect on combined exposure of alectinib and M4 due to CYP3A4 induction by carbamazepine is not expected. M4 is an in vitro a substrate of P-gp and concentrations may decrease due to P-gp induction by carbamazepine. However, as alectinib inhibits P-gp, it is not expected that coadministration with carbamazepine will have a clinically relevant effect on M4 exposure.

Description:

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No Interaction Expected

Alectinib

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 CYPs 2C9 and 1A2. Alectinib does not inhibit or induce UGTs or CYPs. Carvedilol is also an inhibitor of P-gp. However the clinical relevance of P-gp inhibition by carvedilol is unknown. M4, the active metabolite of alectinib, is an in vitro substrate of P-gp and concentrations may decrease due to inhibition by carvedilol. However, as alectinib inhibits P-gp, it is not expected that coadministration with carvedilol will have a clinically relevant effect on M4 exposure.

Description:

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No Interaction Expected

Alectinib

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. Alectinib does not interact with this metabolic pathway.

Description:

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No Interaction Expected

Alectinib

Cefalexin

Quality of Evidence: Very Low

Summary:

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

Description:

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No Interaction Expected

Alectinib

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

Description:

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No Interaction Expected

Alectinib

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. Alectinib is unlikely to interfere with this elimination pathway.

Description:

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No Interaction Expected

Alectinib

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

Description:

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No Interaction Expected

Alectinib

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. Alectinib is unlikely to interfere with this elimination pathway.

Description:

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No Interaction Expected

Alectinib

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. Alectinib is unlikely to interfere with this elimination pathway.

Description:

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No Interaction Expected

Alectinib

Celecoxib

Quality of Evidence: Very Low

Summary:

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

Description:

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No Interaction Expected

Alectinib

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

Description:

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Potential Weak Interaction

Alectinib

Chloramphenicol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Chloramphenicol is predominantly glucuronidated. In vitro studies have shown that chloramphenicol can inhibit metabolism mediated by CYP3A4 (strong), CYP2C19 (strong) and CYP2D6 (weak). Alectinib is metabolised by CYP3A4 to its active metabolite M4 and combined exposure may alter due to strong inhibition by chloramphenicol. After coadministration with posaconazole, a strong CYP3A4 inhibitor, exposure of alectinib and its active metabolite M4 increased by 36%. A similar effect may occur after coadministration with chloramphenicol. Therefore, monitoring for alectinib toxicity should be considered. 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:

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No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

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No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

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No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

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No Interaction Expected

Alectinib

Chlortalidone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Chlortalidone is mainly excreted unchanged in the urine and faeces. OAT1/3 are the major transporters of loop and thiazide diuretics, which are not affected by alectinib. 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. Alectinib is unlikely to interfere with this metabolic or elimination pathway.

Description:

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Potential Weak Interaction

Alectinib

Ciclosporin (Cyclosporine)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Ciclosporin is a substrate of CYP3A4. Alectinib does not inhibit or induce CYPs. Ciclosporin inhibits OATP1B1 and CYP3A4. Exposure to alectinib and its active metabolite M4 may increase due to inhibition of CYP3A4 by ciclosporin, but this is unlikely to be clinically significant. Ciclosporin is also a substrate of P-gp and concentrations may increase due to inhibition by alectinib and M4. Monitoring for ciclosporin toxicity should be considered.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib is unlikely to interfere with this elimination pathway.

Description:

See summary

No Interaction Expected

Alectinib

Cimetidine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cimetidine is metabolised by CYP450 enzymes. Alectinib 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. Exposure to alectinib and its active metabolite M4 may increase due to inhibition of CYP3A4 by cimetidine, but this is unlikely to be clinically significant.

Description:

See summary

No Interaction Expected

Alectinib

Ciprofloxacin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ciprofloxacin is primarily eliminated unchanged by the kidneys by glomerular filtration and tubular secretion via OAT3. It is also metabolised and partially cleared through the bile and intestine. Alectinib is unlikely to interfere with this elimination or metabolic pathway. Ciprofloxacin is also a weak to moderate inhibitor of CYP3A4 and a strong inhibitor of CYP1A2. Exposure to alectinib and its active metabolite M4 may increase due to inhibition of CYP3A4 by ciprofloxacin, but this is unlikely to be clinically significant.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

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%). Alectinib does not inhibit or induce CYPs.

Description:

See summary

Potential Weak Interaction

Alectinib

Clarithromycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Clarithromycin is metabolised by CYP3A4. Alectinib does not inhibit or induce CYPs. Clarithromycin is also an inhibitor of CYP3A4 (strong) and P-gp. Alectinib is metabolised by CYP3A4 to its active metabolite M4 and combined exposure may alter due to strong inhibition by clarithromycin. After coadministration with posaconazole, a strong CYP3A4 inhibitor, exposure of alectinib and its active metabolite M4 increased by 36%. A similar effect may occur after coadministration with clarithromycin Therefore, monitoring for alectinib toxicity should be considered. M4 is also an in vitro substrate of P-gp. However, as alectinib inhibits P-gp, it is not expected that coadministration with clarithromycin will have a clinically relevant effect on M4 exposure.

Description:

See summary

No Interaction Expected

Alectinib

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

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

Clindamycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clindamycin is metabolised by CYP3A4. Alectinib does not inhibit or induce CYPs. In vitro data suggest that clindamycin is a CYP3A4 inhibitor. Exposure to alectinib and its active metabolite M4 may increase due to inhibition of CYP3A4 by clindamycin, but this is unlikely to be clinically significant.

Description:

See summary

No Interaction Expected

Alectinib

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

Alectinib

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. Alectinib is unlikely to interfere with this elimination pathway. In vitro data suggest that clofazimine is a moderate to strong CYP3A4 inhibitor. Alectinib is metabolised by CYP3A4 to its active metabolite M4 and combined exposure may alter due to inhibition by clofazimine. After coadministration with posaconazole, a strong CYP3A4 inhibitor, exposure of alectinib and its active metabolite M4 increased by 36%. A similar effect may occur after coadministration with clofazimine. Therefore, monitoring for alectinib toxicity should be considered.

Description:

See summary

No Interaction Expected

Alectinib

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

Description:

See summary

No Interaction Expected

Alectinib

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. In addition, clomipramine and desmethylclomipramine are metabolised by CYP2D6. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

Clonidine

Quality of Evidence: Very Low

Summary:

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

Description:

See summary

No Interaction Expected

Alectinib

Clopidogrel

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clopidogrel is a prodrug and is converted to its active metabolite mainly through CYP2C19 with CYP3A4, 2B6 and 1A2 playing a minor role. Moreover, clopidogrel is an inhibitor of CYP2C8 (strong), CYP2B6 (weak) and in vitro of CYP2C9 at high concentrations. The clinical relevance of CYP2C9 inhibition is unknown. Alectinib does not interact with this metabolic pathway.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs or UGTs.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib is unlikely to interfere with this elimination pathway.

Description:

See summary

No Interaction Expected

Alectinib

Clozapine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clozapine is metabolised mainly by CYP1A2 and CYP3A4, and to a lesser extent by CYP2C19 and CYP2D6. Alectinib does not inhibit or induce CYPs.

Description:

See summary

Potential Weak Interaction

Alectinib

Codeine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Codeine is converted via CYP2D6 to morphine, an active metabolite with analgesic and opioid properties. Morphine is further metabolized by conjugation with glucuronic acid to morphine-3-glucuronide (inactive) and morphine-6-glucuronide (active). Codeine is converted via CYP3A4 to norcodeine, an inactive metabolite. Alectinib does not inhibit or induce CYPs or UGTs. Additionally, the metabolite morphine is a substrate of P-gp and concentrations may increase due to inhibition by alectinib and its active metabolite M4. Monitoring for morphine toxicity should be considered.

Description:

See summary

Potential Weak Interaction

Alectinib

Colchicine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Colchicine is metabolised by CYP3A4. Alectinib does not inhibit or induce CYPs. Colchicine is also a substrate of P-gp and concentrations may increase due to inhibition by alectinib and its active metabolite M4. Monitoring for colchicine toxicity should be considered.

Description:

See summary

No Interaction Expected

Alectinib

Cycloserine

Quality of Evidence: Very Low

Summary:

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

Description:

See summary

Potential Interaction

Alectinib

Dabigatran

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Dabigatran is renally excreted. Alectinib is unlikely to interfere with this elimination pathway. Dabigatran is also a substrate of P-gp and concentrations may increase due to inhibition by alectinib and its active metabolite M4. Administration of dabigatran should occur 2 hours before alectinib, in a fasted state to circumvent the potential intestinal P-gp interaction. Monitor closely for dabigatran toxicity.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib is unlikely to interfere with this elimination pathway.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

Dexamethasone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dexamethasone is a substrate of CYP3A4. Alectinib does not inhibit or induce CYPs. Dexamethasone has also been described as a weak inducer of CYP3A4. Alectinib is metabolised by CYP3A4 to its active metabolite M4 and combined exposure may alter due to induction by dexamethasone. However, after coadministration with rifampicin, a strong CYP3A4 inducer, combined exposure of alectinib and M4 reduced by only 18%. Therefore, a clinically relevant effect on combined exposure of alectinib and M4 due to CYP3A4 induction by dexamethasone is not expected. Furthermore, CYP3A4 induction by dexamethasone has not yet been established.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

Potential Weak Interaction

Alectinib

Diamorphine (diacetylmorphine)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. 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). Alectinib does not inhibit or induce UGTs. Additionally, morphine is a substrate of P-gp and concentrations may increase due to inhibition by alectinib and its active metabolite M4. Monitoring for morphine toxicity should be considered.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs or UGTs.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce UGTs or CYPs.

Description:

See summary

Potential Weak Interaction

Alectinib

Digoxin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Digoxin is eliminated renally via the renal transporters OATP4C1 and P-gp. Digoxin concentrations may increase due to P-gp inhibition by alectinib and its active metabolite M4. Monitoring for digoxin toxicity should be considered

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce UGTs or CYPs.

Description:

See summary

No Interaction Expected

Alectinib

Diltiazem

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Diltiazem is metabolised by CYP3A4 and CYP2D6. Alectinib does not inhibit or induce CYPs. Diltiazem is also an inhibitor of CYP3A4 (moderate). Exposure to alectinib and its active metabolite M4 may increase due to inhibition of CYP3A4 by diltiazem, but this is unlikely to be clinically significant. Moreover, diltiazem is an inhibitor of P-gp. The clinical relevance of P-gp inhibition by diltiazem is unknown. M4 is an in vitro substrate of P-gp and concentrations may increase due to inhibition by dilitiazem. However, as alectinib inhibits P-gp, it is not expected that coadministration with diltiazem will have a clinically relevant effect on M4 exposure.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not interact with this metabolic pathway.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce UGTs.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs and is unlikely to interfere with this elimination pathway.

Description:

See summary

No Interaction Expected

Alectinib

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%). Alectinib does not inhibit or induce CYPs or UGTs.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce 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 alectinib, or to be affected if co-administered with alectinib.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib is unlikely to interfere with this elimination pathway.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not interact with this metabolic pathway. Dulaglutide delays gastric emptying and could possibly decrease the absorption rate of concomitantly administered oral drugs. The clinical relevance of delayed absorption is considered to be limited.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

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). Alectinib does not inhibit or induce CYPs.

Description:

See summary

Potential Weak Interaction

Alectinib

Edoxaban

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Edoxaban is partially metabolised by CYP3A4 (<10%). Alectinib does not inhibit or induce CYPs. Edoxaban is also a substrate of P-gp and concentrations may increase due to inhibition by alectinib and its active metabolite M4. Monitoring for edoxaban toxicity should be considered.

Description:

See summary

No Interaction Expected

Alectinib

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

Description:

See summary

No Interaction Expected

Alectinib

Enalapril

Quality of Evidence: Very Low

Summary:

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

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib is unlikely to interfere with this elimination pathway.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib is unlikely to interfere with this elimination pathway.

Description:

See summary

No Interaction Expected

Alectinib

Ertapenem

Quality of Evidence: Very Low

Summary:

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

Description:

See summary

Potential Weak Interaction

Alectinib

Erythromycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Erythromycin is an inhibitor of CYP3A4 (moderate) and P-gp. Exposure to alectinib and its active metabolite M4 may increase due to inhibition of CYP3A4 by erythromycin, but this is unlikely to be clinically significant. M4 is an in vitro substrate of P-gp and concentrations may increase due to inhibition by erythromycin. However, as alectinib inhibits P-gp, it is not expected that coadministration with erythromycin will have a clinically relevant effect on M4 exposure. Erythromycin is also a substrate of CYP3A4. Alectinib does not inhibit or induce CYPs. Furthermore, erythromycin is a substrate of P-gp and concentrations may increase due to inhibition by alectinib and M4. Therefore, monitoring for erythromycin toxicity should be considered.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

Esomeprazole

Quality of Evidence: Low

Summary:

Coadministration has been studied and a clinically significant interaction is unlikely. Esomeprazole is metabolised by CYP2C19 and CYP3A4. Esomeprazole is also an inhibitor of CYP2C19. Alectinib does not interact with this metabolic pathway. In healthy subjects (n=24) coadministration of alectinib (600 mg single dose) and esomeprazole (40 mg daily for 5 days) resulted in combined exposure of alectinib and its active metabolite M4 increasing by only 17%. Therefore, no clinically relevant effect on alectinib and M4 combined exposure is expected due to pH elevation caused by esomeprazole.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs or UGTs.

Description:

See summary

No Interaction Expected

Alectinib

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

Description:

See summary

No Interaction Expected

Alectinib

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

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not interact with this metabolic pathway.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

Potential Weak Interaction

Alectinib

Everolimus (Immunosuppressant)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Everolimus is mainly metabolised by CYP3A4. Alectinib does not inhibit or induce CYPs. Everolimus is also a substrate of P-gp and concentrations may increase due to inhibition by alectinib and its active metabolite M4. Monitoring for everolimus toxicity should be considered.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib is unlikely to interfere with this elimination pathway. Exenatide delays gastric emptying and could possibly decrease the absorption rate of concomitantly administered oral drugs. The clinical relevance of delayed absorption is considered to be limited.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce UGTs.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce OATs. Combined exposure of alectinib and its active metabolite M4 increased by only 17% after coadministration with the proton-pump inhibitor esomeprazole. A similar effect may occur after coadministration with famotidine. Therefore, no clinically relevant effect on alectinib and M4 combined exposure is expected due to pH elevation caused by famotidine.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not interact with this metabolic pathway.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

Potential Weak Interaction

Alectinib

Fexofenadine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Fexofenadine is a substrate of P-gp and concentrations may increase due to inhibition by alectinib and its active metabolite M4. Monitoring for fexofenadine toxicity should be considered.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

Fish oils

Quality of Evidence: Very Low

Summary:

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

Description:

See summary

No Interaction Expected

Alectinib

Flecainide

Quality of Evidence: Very Low

Summary:

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

Description:

See summary

No Interaction Expected

Alectinib

Flucloxacillin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Flucloxacillin is mainly renally eliminated partly by glomerular filtration and partly by active secretion via OAT1. Alectinib is unlikely to interfere with this elimination pathway. Flucloxacillin is described as a CYP3A4 inducer. However, the mechanism and clinical relevance of this interaction is unknown. Alectinib is metabolised by CYP3A4 to its active metabolite M4 and combined exposure may alter due to induction by flucloxacillin. However, after coadministration with rifampicin, a strong CYP3A4 inducer, combined exposure of alectinib and M4 reduced by only 18%. Therefore, a clinically relevant effect on combined exposure of alectinib and M4 due to CYP3A4 induction by flucloxacillin is not expected.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib is unlikely to interfere with this elimination pathway. Fluconazole is also an inhibitor of CYPs 3A4 (moderate), 2C9 (moderate) and 2C19 (strong). Exposure to alectinib and its active metabolite M4 may increase due to inhibition of CYP3A4 by fluconazole, but this is unlikely to be clinically significant.

Description:

See summary

No Interaction Expected

Alectinib

Flucytosine

Quality of Evidence: Very Low

Summary:

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

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not interact with this metabolic pathway.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not interact with this metabolic pathway.

Description:

See summary

No Interaction Expected

Alectinib

Fluvoxamine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fluvoxamine is metabolised mainly by CYP2D6 and to a lesser extent by CYP1A2. Alectinib does not inhibit or induce CYPs. Fluvoxamine is also an inhibitor of CYPs 1A2 (strong), 2C19 (strong), 3A4 (moderate), 2C9 (weak-moderate) and CYP2D6 (weak). Exposure to alectinib and its active metabolite M4 may increase due to inhibition of CYP3A4 by fluvoxamine, but this is unlikely to be clinically significant.

Description:

See summary

No Interaction Expected

Alectinib

Fondaparinux

Quality of Evidence: Very Low

Summary:

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

Description:

See summary

No Interaction Expected

Alectinib

Formoterol

Quality of Evidence: Very Low

Summary:

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

Description:

See summary

No Interaction Expected

Alectinib

Fosaprepitant

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fosaprepitant is rapidly, almost completely, converted to the active metabolite aprepitant. Aprepitant is mainly metabolized by CYP3A4 and to a lesser extent by CYP1A2 and CYP2C19. Alectinib does not inhibit or induce CYPs. During treatment aprepitant is a moderate inhibitor of CYP3A4. Exposure to alectinib and its active metabolite M4 may increase due to inhibition of CYP3A4 by aprepitant, but this is unlikely to be clinically significant. After treatment aprepitant is a weak inducer of CYP3A4, CYP2C9 and UGT. Alectinib is metabolised by CYP3A4 to its active metabolite M4 and combined exposure may alter due to induction by aprepitant. However, after coadministration with rifampicin, a strong CYP3A4 inducer, combined exposure of alectinib and M4 reduced by only 18%. Therefore, a clinically relevant effect on combined exposure of alectinib and M4 due to CYP3A4 induction by aprepitant is not expected.

Description:

See summary

No Interaction Expected

Alectinib

Fosphenytoin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fosphenytoin is rapidly converted to the active metabolite phenytoin. Phenytoin is mainly metabolized by CYP2C9 and to a lesser extent by CYP2C19. Alectinib does not inhibit or induce CYPs. Phenytoin is a potent inducer of CYP3A4 and UGT. Alectinib is metabolised by CYP3A4 to its active metabolite M4 and combined exposure may alter due to induction by phenytoin. However, after coadministration with rifampicin, a strong CYP3A4 inducer, combined exposure of alectinib and M4 reduced by only 18%. Therefore, a clinically relevant effect on combined exposure of alectinib and M4 due to CYP3A4 induction by phenytoin is not expected. Moreover, fosphenytoin is an inducer of P-gp. M4 is an in vitro a substrate of P-gp and concentrations may decrease due to induction by fosphenytoin. However, as alectinib inhibits P-gp, it is not expected that coadministration with fosphenytoin will have a clinically relevant effect on M4 exposure.

Description:

See summary

No Interaction Expected

Alectinib

Furosemide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Furosemide is glucuronidated mainly in the kidney (UGT1A9) and to a lesser extent in the liver (UGT1A1). A large proportion of furosemide is also eliminated unchanged renally (via OATs). OAT1/3 are the major transporters of loop and thiazide diuretics, which are not affected by alectinib. 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. Alectinib is unlikely to interfere with this metabolic or elimination pathway.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib is unlikely to interfere with this elimination pathway.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not interact with this metabolic pathway.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib is unlikely to interfere with this elimination pathway.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

Potential Weak Interaction

Alectinib

Granisetron

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Granisetron is metabolised by CYP3A4. Alectinib does not inhibit or induce CYPs. Granisetron is also a substrate of P-gp and concentrations may increase due to inhibition by alectinib and its active metabolite M4. Monitoring for granisetron toxicity should be considered.

Description:

See summary

Potential Weak Interaction

Alectinib

Grapefruit juice

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Grapefruit juice is known to inhibit CYP3A4 enzymes. Alectinib is metabolised by CYP3A4 to its active metabolite M4 and combined exposure may alter due to inhibition by grapefruit juice. After coadministration with posaconazole, a strong CYP3A4 inhibitor, exposure of alectinib and its active metabolite M4 increased by 36%. A similar effect may occur after coadministration with grapefruit juice. Therefore, monitoring for alectinib toxicity should be considered

Description:

See summary

No Interaction Expected

Alectinib

Green tea

Quality of Evidence: Very Low

Summary:

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

Description:

See summary

No Interaction Expected

Alectinib

Griseofulvin

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 1% of a griseofulvin dose is excreted unchanged via the kidneys. Griseofulvin is also a liver microsomal enzyme inducer and may lower plasma levels, and therefore reduce the efficacy of concomitantly administered medicinal products that are metabolised by CYPs, such as alectinib. Alectinib is metabolised by CYP3A4 to its active metabolite M4 and combined exposure may alter due to induction by griseofulvin. However, after coadministration with rifampicin, a strong CYP3A4 inducer, alectinib and M4 combined exposure reduced by only 18%. Therefore, a clinically relevant effect on alectinib and M4 combined exposure due to CYP3A4 induction by griseofulvin is not expected.

Description:

See summary

No Interaction Expected

Alectinib

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

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not interact with this metabolic pathway.

Description:

See summary

No Interaction Expected

Alectinib

Hydralazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Hydralazine is metabolised via primary oxidative metabolism and acetylation. Alectinib does not interact with this metabolic pathway. In vitro studies have suggested that hydralazine is a mixed enzyme inhibitor, which may weakly inhibit CYP3A4 and CYP2D6. Exposure to alectinib and its active metabolite M4 may increase due to inhibition of CYP3A4 by hydralazine, but this is unlikely to be clinically significant.

Description:

See summary

No Interaction Expected

Alectinib

Hydrochlorothiazide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Hydrochlorothiazide is not metabolised and is cleared by the kidneys via OAT1. OAT1/3 are the major transporters of loop and thiazide diuretics, which are not affected by alectinib. 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. Alectinib is unlikely to interfere with this elimination pathway and does not inhibit or induce OATs.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

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

Alectinib

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. Alectinib does not inhibit or induce UGTs.

Description:

See summary

No Interaction Expected

Alectinib

Hydroxyurea (Hydroxycarbamide)

Quality of Evidence: Very Low

Summary:

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

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not interact with this metabolic pathway.

Description:

See summary

No Interaction Expected

Alectinib

Ibandronic acid

Quality of Evidence: Very Low

Summary:

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

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs or UGTs.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib is unlikely to interfere with this elimination pathway.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

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, which are not affected by alectinib. 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. Alectinib does not inhibit or induce CYPs or OATs.

Description:

See summary

No Interaction Expected

Alectinib

Insulin

Quality of Evidence: Very Low

Summary:

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

Description:

See summary

No Interaction Expected

Alectinib

Interferon alpha

Quality of Evidence: Very Low

Summary:

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

Description:

See summary

No Interaction Expected

Alectinib

Interleukin 2 (Aldesleukin)

Quality of Evidence: Very Low

Summary:

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

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not interact with this metabolic pathway.

Description:

See summary

No Interaction Expected

Alectinib

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

Description:

See summary

No Interaction Expected

Alectinib

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

Alectinib

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. Alectinib is unlikely to interfere with this metabolic pathway.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

Potential Weak Interaction

Alectinib

Itraconazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Itraconazole is primarily metabolised by CYP3A4. Alectinib does not inhibit or induce CYPs. Itraconazole is also an inhibitor of CYP3A4 (strong), CYP2C9 (weak), P-gp and BCRP. Alectinib is metabolised by CYP3A4 to its active metabolite M4 and combined exposure may alter due to strong inhibition by itraconazole. After coadministration with posaconazole, a strong CYP3A4 inhibitor, exposure of alectinib and its active metabolite M4 increased by 36%. A similar effect may occur after coadministration with itraconazole. Therefore, monitoring for alectinib toxicity should be considered. M4 is also an in vitro substrate of P-gp and concentrations may decrease due to inhibition by itraconazole. However, as alectinib inhibits P-gp, it is not expected that coadministration with itraconazole will have a clinically relevant effect on M4 exposure.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib is unlikely to interfere with this elimination pathway.

Description:

See summary

Potential Weak Interaction

Alectinib

Ketoconazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Ketoconazole is a substrate of CYP3A4. Alectinib does not inhibit or induce CYPs. Ketoconazole is also an inhibitor of CYP3A4 (strong) and P-gp. Alectinib is metabolised by CYP3A4 to its active metabolite M4 and combined exposure may alter due to strong inhibition by ketoconazole. After coadministration with posaconazole, a strong CYP3A4 inhibitor, exposure of alectinib and its active metabolite M4 increased by 36%. A similar effect may occur after coadministration with ketoconazole. Therefore, monitoring for alectinib toxicity should be considered. M4 is also an in vitro substrate of P-gp and concentrations may increase due to inhibition by ketoconazole. However, as alectinib inhibits P-gp, it is not expected that coadministration with ketoconazole will have a clinically relevant effect on M4 exposure.

Description:

See summary

No Interaction Expected

Alectinib

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). Alectinib does not inhibit or induce UGTs.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not interact with this metabolic pathway.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs. Combined exposure of alectinib and its active metabolite M4 increased by only 17% after coadministration with the proton-pump inhibitor esomeprazole. A similar effect may occur after coadministration with lansoprazole. Therefore, no clinically relevant effect on alectinib and M4 combined exposure is expected due to pH elevation caused by lansoprazole.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib is unlikely to interfere with this elimination pathway.

Description:

See summary

No Interaction Expected

Alectinib

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

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

Levonorgestrel

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Levonorgestrel mainly is metabolised by CYP3A4 and is glucuronidated to a minor extent. Alectinib does not inhibit or induce CYPs or UGTs.

Description:

See summary

No Interaction Expected

Alectinib

Levonorgestrel (Emergency Contraception)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Levonorgestrel is mainly metabolised by CYP3A4 and is glucuronidated to a minor extent. Alectinib does not inhibit or induce CYPs or UGTs.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not interact with this metabolic pathway.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

Potential Weak Interaction

Alectinib

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. Alectinib is unlikely to interfere with this elimination pathway and does not inhibit or induce CYPs. Linagliptin is a weak inhibitor of CYP3A4. Exposure to alectinib and its active metabolite M4 may increase due to inhibition of CYP3A4 by linagliptin, but this is unlikely to be clinically significant. Linagliptin is also a substrate of P-gp and concentrations may increase due to inhibition by alectinib and M4. Monitoring for linagliptin toxicity should be considered.

Description:

See summary

No Interaction Expected

Alectinib

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

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not interact with this metabolic pathway.

Description:

See summary

No Interaction Expected

Alectinib

Lisinopril

Quality of Evidence: Very Low

Summary:

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

Description:

See summary

No Interaction Expected

Alectinib

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 with alectinib is expected.

Description:

See summary

No Interaction Expected

Alectinib

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 but based on metabolism and clearance a clinically significant interaction is unlikely. 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. However alectinib is not an immunosuppressant, immunomodulatory or bone marrow toxic drug. Therefore, no pharmacodynamic interaction is expected with live vaccines.

Description:

See summary

Potential Weak Interaction

Alectinib

Loperamide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Loperamide is mainly metabolised by CYP3A4 and CYP2C8. Alectinib does not inhibit or induce CYPs. Loperamide is also a substrate of P-gp and concentrations may increase due to inhibition by alectinib and its active metabolite M4. Monitoring for loperamide toxicity should be considered.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

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

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce UGTs.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib is unlikely to interfere with this elimination pathway. When used as antacid, exposure may increase due to pH elevation. Combined exposure of alectinib and its active metabolite M4 increased by 17% only after coadministration with the proton-pump inhibitor esomeprazole. A similar effect may occur after coadministration with magnesium. Therefore, no clinically relevant effect on alectinib and M4 combined exposure is expected due to pH elevation caused by magnesium.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

Medroxyprogesterone (non-depot)

Quality of Evidence: Very Low

Summary:

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs or UGTs.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib is unlikely to interfere with this elimination pathway.

Description:

See summary

No Interaction Expected

Alectinib

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

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not interact with this metabolic pathway.

Description:

See summary

No Interaction Expected

Alectinib

Metamizole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. 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%). Afatinib is unlikely to interfere with this metabolic or elimination pathway. Metamizole is also an inducer of CYP3A4. Alectinib is metabolised by CYP3A4 to its active metabolite M4 and combined exposure may alter due to induction by metamizole. However, after coadministration with rifampicin, a strong CYP3A4 inducer, combined exposure of alectinib and M4 reduced by only 18%. Therefore, a clinically relevant effect on combined exposure of alectinib and M4 due to CYP3A4 induction by metamizole is not expected.

Description:

See summary

No Interaction Expected

Alectinib

Metformin

Quality of Evidence: Very Low

Summary:

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

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib is unlikely to interfere with this elimination pathway.

Description:

See summary

No Interaction Expected

Alectinib

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 methyphenidate to affect disposition of alectinib, or to be affected if co-administered with alectinib.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

Metoclopramide

Quality of Evidence: Very Low

Summary:

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

Description:

See summary

No Interaction Expected

Alectinib

Metolazone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metolazone is largely excreted unchanged in the urine. OAT1/3 are the major transporters of loop and thiazide diuretics, which are not affected by alectinib. 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. Alectinib is unlikely to interfere with this elimination pathway and does not inhibit or induce OATs.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib 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). Therefore, an effect on alectinib and M4 combined exposure caused by metronidazole is not expected.

Description:

See summary

No Interaction Expected

Alectinib

Mexiletine

Quality of Evidence: Very Low

Summary:

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

Description:

See summary

No Interaction Expected

Alectinib

Mianserin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Mianserin is metabolised by CYPs 2D6 and 1A2, and to a lesser extent by CYP3A4. Alectinib does not inhibit or induce CYPs.

Description:

See summary

Potential Weak Interaction

Alectinib

Miconazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Miconazole is extensively metabolized by the liver. Miconazole is also an inhibitor of CYP2C9 (moderate) and CYP3A4 (strong). Alectinib is metabolised by CYP3A4 to its active metabolite M4 and combined exposure may alter due to strong inhibition by miconazole. After coadministration with posaconazole, a strong CYP3A4 inhibitor, exposure of alectinib and its active metabolite M4 increased by 36%. A similar effect may occur after coadministration with miconazole. Therefore, monitoring for alectinib toxicity should be considered. Note: after dermal application miconazole is only minimally absorbed. Therefore, no clinical relevant interaction is expected.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

Midazolam (parenteral)

Quality of Evidence: Very Low

Summary:

Description:

See summary

No Interaction Expected

Alectinib

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

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

Montelukast

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Montelukast is mainly metabolised by CYP2C8 and to a lesser extent by CYPs 3A4 and 2C9. Alectinib does not inhibit or induce CYPs.

Description:

See summary

Potential Weak Interaction

Alectinib

Morphine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Morphine is mainly glucuronidated to morphine-3-glucuronide (UGT2B7>UGT1A1) and, to a lesser extent, to the pharmacologically active morphine-6-glucuronide (UGT2B7>UGT1A1). Alectinib does not inhibit or induce UGTs. Additionally, morphine is a substrate of P-gp and concentrations may increase due to inhibition by alectinib and its active metabolite M4. Monitoring for morphine toxicity should be considered.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce UGTs.

Description:

See summary

No Interaction Expected

Alectinib

Mycophenolate

Quality of Evidence: Very Low

Summary:

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

Description:

See summary

No Interaction Expected

Alectinib

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 exreted renally by a nonsaturable mechanism. Alectinib is unlikely to interfere with this elimination pathway.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not interact with this metabolic pathway.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce UGTs or CYPs.

Description:

See summary

No Interaction Expected

Alectinib

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%). Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

Potential Weak Interaction

Alectinib

Nefazodone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Nefazodone is metabolised mainly by CYP3A4 and is also a strong inhibitor of CYP3A4. Alectinib is metabolised by CYP3A4 to its active metabolite M4 and combined exposure may alter due to strong inhibition by nefazodone. After coadministration with posaconazole, a strong CYP3A4 inhibitor, exposure of alectinib and its active metabolite M4 increased by 36%. A similar effect may occur after coadministration with nefazodone. Therefore, monitoring for alectinib toxicity should be considered.

Description:

See summary

No Interaction Expected

Alectinib

Nicardipine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nicardipine is metabolised mainly by CYP3A4 and to a lesser extent by CYP2D6 and CYP2C8. Alectinib does not inhibit or induce CYPs. Moreover, nicardipine is a weak inhibitor of CYP3A4. Exposure to alectinib and its active metabolite M4 may increase due to inhibition of CYP3A4 by nicardipine, but this is unlikely to be clinically significant.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not interact with this metabolic pathway.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

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

Description:

See summary

No Interaction Expected

Alectinib

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). Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

Norethisterone (Norethindrone)

Quality of Evidence: Very Low

Summary:

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

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs or UGTs.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs

Description:

See summary

No Interaction Expected

Alectinib

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

Alectinib

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. Alectinib is unlikely to interfere with this elimination pathway.

Description:

See summary

No Interaction Expected

Alectinib

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

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib is unlikely to interfere with this elimination pathway.

Description:

See summary

No Interaction Expected

Alectinib

Omeprazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but 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. Alectinib does not interact with this metabolic pathway. Combined exposure of alectinib and its active metabolite M4 increased by 17% only after coadministration with the proton-pump inhibitor esomeprazole. A similar effect may occur after coadministration with omeprazole. Therefore, no clinically relevant effect on alectinib and M4 combined exposure is expected due to pH elevation caused by omeprazole.

Description:

See summary

Potential Weak Interaction

Alectinib

Ondansetron

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Ondansetron is metabolised mainly by CYP1A2 and CYP3A4 and to a lesser extent by CYP2D6. Alectinib does not inhibit or induce CYPs. Ondansetron is also a substrate of P-gp and concentrations may increase due to inhibition by alectinib and its active metabolite M4. Monitoring for ondansetron toxicity should be considered.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce UGTs.

Description:

See summary

No Interaction Expected

Alectinib

Oxcarbazepine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Oxcarbazepine is extensively metabolized to the active metabolite monohydroxyderivate (MHD) through cytosolic enzymes. Alectinib does not interact with this metabolic pathway. Both oxcarbazepine and MHD are inducers of CYP3A4 (moderate) and CYP3A5 and are inhibitors of CYP2C19. Alectinib is metabolised by CYP3A4 to its active metabolite M4 and combined exposure may alter due to induction by oxcarbazepine. However, after coadministration with rifampicin, a strong CYP3A4 inducer, combined exposure of alectinib and M4 reduced by only 18%. Therefore, a clinically relevant effect on combined exposure of alectinib and M4 due to CYP3A4 induction by oxcarbazepine is not expected.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce UGTs.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

Paliperidone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Paliperidone is primarily eliminated renally (possibly via OCT) with minimal metabolism occurring via CYP2D6 and CYP3A4. Alectinib is unlikely to interfere with this elimination pathway and does not inhibit or induce OCTs or CYPs.

Description:

See summary

Potential Weak Interaction

Alectinib

Palonosetron

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Palonosetron is metabolised mainly by CYP3A4 and to a lesser extent by CYP2D6 and CYP1A2. Alectinib does not inhibit or induce CYPs. Palonosetron is also a substrate of P-gp and concentrations may increase due to inhibition by alectinib and its active metabolite M4. Monitoring for palonosetron toxicity should be considered.

Description:

See summary

No Interaction Expected

Alectinib

Pamidronic acid

Quality of Evidence: Very Low

Summary:

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

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs. Combined exposure of alectinib and its active metabolite M4 increased by only 17% after coadministration with the proton-pump inhibitor esomeprazole. A similar effect may occur after coadministration with pantoprazole. Therefore, no clinically relevant effect on alectinib and M4 combined exposure is expected due to pH elevation caused by pantoprazole.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib is unlikely to interfere with this elimination pathway.

Description:

See summary

No Interaction Expected

Alectinib

Paracetamol (Acetaminophen)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Paracetamol is mainly metabolised by glucuronidation (via UGTs 1A9 (major), 1A6, 1A1, and 2B15) and sulfation and, to a lesser extent, by oxidation (CYPs 2E1 (major), 1A2, 3A4 and 2D6). Alectinib does not inhibit or induce UGTs or CYPs.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not interact with this metabolic pathway.

Description:

See summary

No Interaction Expected

Alectinib

Peginterferon alfa-2a

Quality of Evidence: Very Low

Summary:

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

Description:

See summary

No Interaction Expected

Alectinib

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

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs or FMO3.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib is unlikely to interfere with this elimination pathway.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

Phenelzine

Quality of Evidence: Very Low

Summary:

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

Description:

See summary

No Interaction Expected

Alectinib

Phenobarbital (Phenobarbitone)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Phenobarbital is metabolized by CYP2C19 and 2C9 (major pathway) and to a lesser extent by CYP2E1. Alectinib does not inhibit or induce CYPs. Phenobarbital is a strong inducer of CYP3A4, CYP2C9, CYP2C8 and UGTs. Alectinib is metabolised by CYP3A4 to its active metabolite M4 and combined exposure may alter due to induction by phenobarbital. However, after coadministration with rifampicin, a strong CYP3A4 inducer, combined exposure of alectinib and M4 reduced by only 18%. Therefore, a clinically relevant effect on combined exposure of alectinib and M4 due to CYP3A4 induction by phenobarbital is not expected.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

Phenytoin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Phenytoin is mainly metabolized by CYP2C9 and to a lesser extent by CYP2C19. Alectinib does not inhibit or induce CYPs. Phenytoin is a strong inducer of CYP3A4, UGT and P-gp. Alectinib is metabolised by CYP3A4 to its active metabolite M4 and combined exposure may alter due to induction by phenytoin. However, after coadministration with rifampicin, a strong CYP3A4 inducer, combined exposure of alectinib and M4 reduced by only 18%. Therefore, a clinically relevant effect on combined exposure of alectinib and M4 due to CYP3A4 induction by phenytoin is not expected.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs and is unlikely to interfere with this elimination pathway.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

Pitavastatin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pitavastatin is metabolised by UGT1A3 and UGT2B7 with minimal metabolism by CYP2C9 and CYP2C8. Pitavastatin is also a substrate of OATP1B1. Alectinib does not inhibit or induce UGTs, CYPs, or OATs.

Description:

See summary

Potential Weak Interaction

Alectinib

Posaconazole

Quality of Evidence: Low

Summary:

Coadministration has been studied and care should be taken. Posaconazole is primarily metabolised by UGTs. Alectinib does not inhibit or induce UGTs. Posaconazole is a substrate of P-gp and concentrations may increase due to P-gp inhibition by alectinib and its active metabolite M4. Monitoring for posaconazole toxicity should be considered. Posaconazole is also a strong inhibitor of CYP3A4. Alectinib is metabolised by CYP3A4 to its active metabolite M4 and combined exposure will alter due to inhibition by posaconazole. In healthy subjects (n=24), coadministration of alectinib (300 mg single dose, day 1 and 15) and posaconazole (400 mg twice daily, days 8 to 21) resulted in combined exposure of alectinib and M4 increasing by 36%. Therefore, monitoring for alectinib toxicity should be considered.

Description:

See summary

No Interaction Expected

Alectinib

Potassium

Quality of Evidence: Very Low

Summary:

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

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

Pravastatin

Quality of Evidence: Very Low

Summary:

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

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not interact with this metabolic pathway.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

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

Description:

See summary

No Interaction Expected

Alectinib

Prochlorperazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Prochlorperazine is metabolised by CYP2D6 and CYP2C19. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

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

Description:

See summary

Potential Weak Interaction

Alectinib

Prucalopride

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Prucalopride is minimally metabolised and mainly eliminated renally, partly by active secretion by renal transporters. Alectinib is unlikely to interfere with this elimination pathway. Prucalopride is also a substrate of P- gp and concentrations may increase due to inhibition by alectinib and its active metabolite M4. Monitoring for prucalopride toxicity should be considered.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not interact with this metabolic pathway.

Description:

See summary

No Interaction Expected

Alectinib

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

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

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

Description:

See summary

Potential Weak Interaction

Alectinib

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. Alectinib does not inhibit or induce CYPs. Quinidine is a substrate of P-gp and concentrations may increase due to inhibition by alectinib and its active metabolite M4. Therefore, monitoring for quinidine toxicity should be considered. Quinidine is also an inhibitor of CYP2D6 (strong) and CYP3A4 (weak). Exposure to alectinib and its active metabolite M4 may increase due to inhibition of CYP3A4 by quinidine, but this is unlikely to be clinically significant. Quinidine is also an inhibitor of P-gp (moderate). M4 is an in vitro substrate of P-gp and concentrations may increase due to inhibition by quinidine. However, as alectinib inhibits P-gp, it is not expected that coadministration with quinidine will have a clinically relevant effect on M4 exposure.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs. Combined exposure of alectinib and its active metabolite M4 increased by only 17% after coadministration with the proton-pump inhibitor esomeprazole. A similar effect may occur after coadministration with rabeprazole. Therefore, no clinically relevant effect on alectinib and M4 combined exposure is expected due to pH elevation caused by rabeprazole.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not interact with this metabolic pathway.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce OATs. Combined exposure of alectinib and its active metabolite M4 increased by only 17% after coadministration with the proton-pump inhibitor esomeprazole. A similar effect may occur after coadministration with ranitidine. Therefore, no clinically relevant effect on alectinib and M4 combined exposure is expected due to pH elevation caused by ranitidine.

Description:

See summary

Potential Weak Interaction

Alectinib

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. Alectinib does not inhibit or induce CYPs. Ranolazine is a weak inhibitor of P-gp, CYP3A4 and CYP2D6. Exposure to alectinib and its active metabolite M4 may increase due to inhibition of CYP3A4 by ranolazine, but this is unlikely to be clinically significant. M4 is also an in vitro substrate of P-gp and concentrations may increase due to inhibition by ranolazine. However, as alectinib inhibits P-gp, it is not expected that coadministration with ranolazine will have a clinically relevant effect on M4 exposure. Moreover, ranolazine is a substrate of P-gp and concentrations may increase due to inhibition by alectinib and M4. Monitoring for ranolazine toxicity should be considered.

Description:

See summary

No Interaction Expected

Alectinib

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. In vitro data indicate reboxetine to be a weak inhibitor of CYP3A4 but in vivo data showed no inhibitory effect on CYP3A4. Alectinib does not interact with this metabolic pathway.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs or OATs.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not interact with this metabolic pathway.

Description:

See summary

No Interaction Expected

Alectinib

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

No Interaction Expected

Alectinib

Rifabutin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Rifabutin is metabolised by CYP3A4 and via deacetylation. Alectinib does not inhibit or induce CYPs. Rifabutin is also a strong CYP3A4 and P-gp inducer. Alectinib is metabolised by CYP3A4 to its active metabolite M4 and combined exposure may alter due to induction by rifabutin. However, after coadministration with rifampicin, a strong CYP3A4 inducer, combined exposure of alectinib and M4 reduced by only 18%. Therefore, a clinically relevant effect on combined exposure of alectinib and M4 due to CYP3A4 induction by rifabutin is not expected. M4 is also an in vitro substrate of P-gp and concentrations may decrease due to P-gp induction by rifabutin. However, as alectinib inhibits P-gp, it is not expected that coadministration with rifabutin will have a clinically relevant effect on M4 exposure.

Description:

See summary

No Interaction Expected

Alectinib

Rifampicin

Quality of Evidence: Low

Summary:

Coadministration has been studied and a clinically significant interaction is unlikely. Rifampicin is metabolised via deacetylation. Alectinib does not interact with this metabolic pathway. Rifampicin is also a strong CYP3A4 and P-gp inducer. Alectinib is metabolised by CYP3A4 to its active metabolite M4. In healthy subjects (n=24), coadministration of alectinib (600 mg single dose, day 1 and 17) and rifampicin (600 mg daily, day 8 to 20) resulted in combined exposure of alectinib and M4 falling by only 18%. Therefore, a clinically relevant effect on alectinib and M4 combined exposure due to CYP3A4 induction by rifampicin is not expected. M4 is also an in vitro substrate of P-gp. However, as alectinib inhibits P-gp, it is not expected that coadministration with rifampicin will have a clinically relevant effect on M4 exposure.

Description:

See summary

No Interaction Expected

Alectinib

Rifapentine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Rifapentine is metabolised via deacetylation. Alectinib does not interact with this metabolic pathway. Rifapentine is also a strong CYP3A4, CYP2C8 and P-gp inducer. Alectinib is metabolised by CYP3A4 to its active metabolite M4 and combined exposure may alter due to induction by rifapentine. However, after coadministration with rifampicin, a strong CYP3A4 inducer, combined exposure of alectinib and M4 reduced by only 18%. Therefore, a clinically relevant effect on combined exposure of alectinib and M4 due to CYP3A4 induction by rifapentine is not expected. M4 is also an in vitro substrate of P-gp and concentrations may decrease due to P-gp induction by rifapentine. However, as alectinib inhibits P-gp, it is not expected that coadministration with rifapentine will have a clinically relevant effect on M4 exposure.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib is unlikely to interfere with this elimination pathway.

Description:

See summary

Potential Weak Interaction

Alectinib

Risperidone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Risperidone is metabolised by CYP2D6 and to a lesser extent by CYP3A4. Alectinib does not inhibit or induce CYPs. Risperidone is also a substrate of P-gp and concentrations may increase due to inhibition by alectinib and its active metabolite M4. Monitoring for risperidone toxicity should be considered.

Description:

See summary

Do Not Coadminister

Alectinib

Rivaroxaban

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is contra-indicated. Rivaroxaban is partly metabolised in the liver (by CYP3A4, CYP2J2 and hydrolytic enzymes) and partly eliminated unchanged in urine. Alectinib does not inhibit or induce CYPs . Rivaroxaban is also a substrate of P-gp and BCRP. Concentrations may increase due to inhibition of both P-gp and BCRP by alectinib and its active metabolite M4. As any increase in exposure to rivaroxaban increases the risk of toxicity, coadministration is contra-indicated.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

Potential Weak Interaction

Alectinib

Rosuvastatin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Rosuvastatin is largely excreted unchanged in the faeces via OATP1B1. Alectinib does not inhibit or induce OATs. Rosuvastatin is also a substrate of BCRP and concentrations may increase due to inhibition by alectinib and its active metabolite M4. Monitoring for rosuvastatin toxicity should be considered.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not interact with this metabolic pathway.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

Potential Weak Interaction

Alectinib

Saxagliptin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Saxagliptin is mainly metabolised by CYP3A4. Alectinib does not inhibit or induce CYPs. Saxagliptin is also a substrate of P-gp. Saxagliptin concentrations may increase due to P-gp inhibition by alectinib and its active metabolite M4. Monitoring for saxagliptin toxicity should be considered.

Description:

See summary

No Interaction Expected

Alectinib

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

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

Potential Weak Interaction

Alectinib

Simvastatin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Simvastatin is metabolised by CYP3A4 and the active metabolite is a substrate of OATP1B1. Alectinib does not inhibit or induce CYPs or OATs. Simvastatin is also a substrate of BCRP and concentrations may increase due to inhibition by alectinib and its active metabolite M4. Monitoring for simvastatin toxicity should be considered.

Description:

See summary

Potential Weak Interaction

Alectinib

Sirolimus

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Sirolimus is metabolised by CYP3A4. Alectinib does not inhibit or induce CYPs. Sirolimus is also a substrate of P-gp and concentrations may increase due to inhibition by alectinib and its active metabolite M4. Monitoring for sirolimus toxicity should be considered.

Description:

See summary

Potential Weak Interaction

Alectinib

Sitagliptin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Sitagliptin is primarily eliminated in urine as unchanged drug, metabolism by CYP3A4 represents a minor metabolic pathway. Alectinib does not inhibit or induce CYPs. Sitagliptin elimination occurs via active secretion by OAT3, OATP4C1, and P-gp. Sitagliptin concentrations may increase due to P-gp inhibition by alectinib and its active metabolite M4. Monitoring for sitagliptin toxicity should be considered.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not interact with this metabolic pathway.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib is unlikely to interfere with this elimination pathway.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib is unlikely to interfere with this elimination pathway.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not interact with this metabolic pathway.

Description:

See summary

No Interaction Expected

Alectinib

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

Description:

See summary

No Interaction Expected

Alectinib

St John's Wort

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. St John’s wort is a P-gp and CYP3A4 inducer. Alectinib is metabolised by CYP3A4 to its active metabolite M4 and combined exposure may alter due to induction by St. John’s Wort. However, after coadministration with rifampicin, a strong CYP3A4 inducer, combined exposure of alectinib and M4 reduced by only 18%. Therefore, a clinically relevant effect on combined exposure of alectinib and M4 due to CYP3A4 induction by St John’s Wort is not expected. M4 is also an in vitro substrate of P-gp and concentrations may decrease due to induction by St John’s Wort. However, as alectinib inhibits P-gp, it is not expected that coadministration with St. John’s Wort will have a clinically relevant effect on M4 exposure.

Description:

See summary

No Interaction Expected

Alectinib

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

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib is unlikely to interfere with this elimination pathway.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib is unlikely to interfere with this elimination pathway.

Description:

See summary

No Interaction Expected

Alectinib

Tacrolimus

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tacrolimus is metabolised mainly by CYP3A4. Alectinib does not inhibit or induce CYPs. Tacrolimus is also an inhibitor of CYP3A4 and OATP1B1 in vitro but produced modest inhibition of CYP3A4 and OATP1B1 in the range of clinical concentrations. Exposure to alectinib and its active metabolite M4 may increase due to inhibition of CYP3A4 by tacrolimus, but this is unlikely to be clinically significant.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib is unlikely to interfere with this elimination pathway.

Description:

See summary

Potential Weak Interaction

Alectinib

Telithromycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Telithromycin is metabolised by CYP3A4 (50%) with the remaining 50% metabolised via non-CYP mediated pathways. Alectinib does not interact with this metabolic pathway. Telithromycin is an inhibitor of CYP3A4 (strong). Alectinib is metabolised by CYP3A4 to its active metabolite M4 and combined exposure may alter due to strong inhibition by telithromycin. After coadministration with posaconazole, a strong CYP3A4 inhibitor, combined exposure of alectinib and M4 increased by 36%. A similar effect may occur after coadministration with telithromycin. Therefore, monitoring for alectinib toxicity should be considered. Telithromycin is also an inhibitor of P-gp. M4 is an in vitro substrate of P-gp and concentrations may increase due to inhibition by telithromycin. However, as alectinib inhibits P-gp, it is not expected that coadministration with telithromycin will have a clinically relevant effect on M4 exposure.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce UGTs

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce UGTs.

Description:

See summary

No Interaction Expected

Alectinib

Terbinafine

Quality of Evidence: Very Low

Summary:

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

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib is unlikely to interfere with this elimination pathway.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

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

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib is unlikely to interfere with this elimination pathway.

Description:

See summary

Potential Weak Interaction

Alectinib

Ticagrelor

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Ticagrelor is a substrate of CYP3A4. Alectinib does not inhibit or induce CYPs. Ticagrelor is also a weak inhibitor of CYP3A4. Exposure to alectinib and its active metabolite M4 may increase due to inhibition of CYP3A4 by ticagrelor, but this is unlikely to be clinically significant. Ticagrelor is also a substrate of P-gp and concentrations may increase due to inhibition by alectinib and M4. Monitoring for ticagrelor toxicity should be considered.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs. Note: the systemic absorption of timolol after ocular administration is low.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib is unlikely to interfere with this elimination pathway.

Description:

See summary

No Interaction Expected

Alectinib

Tolbutamide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Tolbutamide is mainly metabolised by CYP2C9 and to a lesser extent by CYPs 2C8 and 2C19. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

Torasemide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Torasemide is metabolised mainly by CYP2C9. Furthermore, OAT1/3 are the major transporters of loop and thiazide diuretics, which are not affected by alectinib. 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. Alectinib does not inhibit or induce CYPs or OATs.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not interact with this metabolic pathway.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib is unlikely to interfere with this elimination pathway.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not interact with this metabolic pathway.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

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 CYP3A4, CYP1A2 and CYP2C9). 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. Alectinib is unlikely to interfere with this elimination pathway and does not interact with these metabolic pathways.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

Potential Weak Interaction

Alectinib

Tropisetron

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Tropisetron is metabolised mainly by CYP2D6. Alectinib does not inhibit or induce CYPs. Tropisetron is also a substrate of P-gp and concentrations may increase due to inhibition by alectinib and its active metabolite M4. Monitoring for tropisetron toxicity should be considered.

Description:

See summary

No Interaction Expected

Alectinib

Ulipristal

Quality of Evidence: Very Low

Summary:

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

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not interact with this metabolic pathway.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib is unlikely to interfere with this elimination pathway.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib is unlikely to interfere with this elimination pathway.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

Verapamil

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Verapamil is metabolised mainly by CYP3A4 and to a lesser extent by CYPs 1A2, 2C8 and 2C9. Alectinib does not inhibit or induce CYPs. Verapamil is also an inhibitor of CYP3A4 (moderate) and P-gp (strong). Exposure to alectinib and its active metabolite M4 may increase due to inhibition of CYP3A4 by verapamil, but this is unlikely to be clinically significant. M4 is also an in vitro substrate of P-gp and concentrations may increase due to inhibition by verapamil. However, as alectinib inhibits P-gp, it is not expected that coadministration with verapamil will have a clinically relevant effect on M4 exposure.

Description:

See summary

Potential Weak Interaction

Alectinib

Vildagliptin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Vildagliptin is inactivated via non-CYP mediated hydrolysis. Alectinib does not interact with this metabolic pathway. Vildagliptin is also a substrate of P-gp and concentrations may increase due to inhibition by alectinib and its active metabolite M4. Monitoring for vildagliptin toxicity should be considered.

Description:

See summary

No Interaction Expected

Alectinib

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 Weak Interaction

Alectinib

Voriconazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Voriconazole is metabolised by CYP2C19 (major pathway) and to a lesser extent by CYP3A4 and CYP2C9. Alectinib does not inhibit or induce CYPs. Voriconazole is also a strong inhibitor of CYP3A4 and a weak inhibitor of CYPs 2C9, 2C19 and 2B6. Alectinib is metabolised by CYP3A4 to its active metabolite M4 and combined exposure may alter due to inhibition by voriconazole. After coadministration with posaconazole, a strong CYP3A4 inhibitor, exposure of alectinib and its active metabolite M4 increased by 36%. A similar effect may occur after coadministration with voriconazole. Therefore, monitoring for alectinib toxicity should be considered.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

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, which are not affected by alectinib. 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. Alectinib is unlikely to interfere with this elimination pathway and does not inhibit or induce OATs.

Description:

See summary

No Interaction Expected

Alectinib

Zaleplon

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Zaleplon is mainly metabolised by aldehyde oxidase and to a lesser extent CYP3A4. Alectinib does not interact with this metabolic pathway.

Description:

See summary

No Interaction Expected

Alectinib

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). Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

Zoledronic acid

Quality of Evidence: Very Low

Summary:

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

Description:

See summary

No Interaction Expected

Alectinib

Zolpidem

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Zolpidem is metabolised mainly by CYP3A4 and to a lesser extent by CYP2C9, CYP2C19, CYP2D6 and CYP1A2. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs.

Description:

See summary

No Interaction Expected

Alectinib

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. Alectinib does not inhibit or induce CYPs or UGTs.

Description:

See summary