Cancer Drug Interactions from Radboud UMC and University of Liverpool

No Interaction Expected

Capmatinib

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. This is not affected by capmatinib.

Description:

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Potential Interaction

Capmatinib

Acenocoumarol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Acenocoumarol is mainly metabolised by CYP2C9 and to a lesser extent by CYP1A2 and CYP2C19. Concentrations may increase due to inhibition of CYP1A2 by capmatinib. After coadministration with caffeine, a CYP1A2 substrate, the AUC of caffeine increased by 134%. Coadministration should be avoided as acenocoumarol toxicity may be increased. If coadministration is unavoidable, monitor closely for acenocoumarol toxicity. Monitor INR/PT and decrease the dose of acenocoumarol in accordance with the label.

Description:

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No Interaction Expected

Capmatinib

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), which is not affected by capmatinib.

Description:

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Potential Interaction

Capmatinib

Agomelatine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Agomelatine is metabolised predominantly via CYP1A2 (90%), with a small proportion metabolised by CYP2C9 and CYP2C19 (10%) and concentrations may increase due to inhibition of CYP1A2 by capmatinib. After coadministration with caffeine, a CYP1A2 substrate, the AUC of caffeine increased by 134%. Coadministration should be avoided as agomelatine toxicity may be increased. If coadministration is unavoidable, monitor closely for agomelatine toxicity and decrease the dose of agomelatine in accordance with the label.

Description:

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Potential Weak Interaction

Capmatinib

Alendronic acid

Quality of Evidence: Very Low

Summary:

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

Description:

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No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

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No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

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Potential Weak Interaction

Capmatinib

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. Aliskiren is also a substrate of P-gp and concentrations may increase due to inhibition of P-gp by capmatinib. After coadministration with digoxin, a P-gp substrate, the AUC of digoxin increased by 47%. Coadministration should be monitored for aliskiren toxicity. No a priori dose adjustment is required.

Description:

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No Interaction Expected

Capmatinib

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, which are not affected by capmatinib. Allopurinol is also an inhibitor of xanthine oxidase, which does not affect capmatinib.

Description:

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Potential Interaction

Capmatinib

Alosetron

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. In vitro data indicate that alosetron is metabolised by CYPs 2C9, 3A4, and 1A2 and concentrations may increase due to inhibition of CYP1A2 by capmatinib. After coadministration with caffeine, a CYP1A2 substrate, the AUC of caffeine increased by 134%. Coadministration should be avoided as alosetron toxicity may be increased. If coadministration is unavoidable, monitor closely for alosetron toxicity and decrease the dose of alosetron in accordance with the label.

Description:

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No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

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No Interaction Expected

Capmatinib

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.

Description:

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Potential Weak Interaction

Capmatinib

Ambrisentan

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Ambrisentan is metabolised by glucuronidation via UGT1A3, UGT1A9, and UGT2B7 and to a lesser extent by CYP3A4 and CYP2C19. This is not affected by capmatinib. Ambrisentan is also a substrate of P-gp and concentrations may increase due to inhibition of P-gp by capmatinib. After coadministration with digoxin, a P-gp substrate, the AUC of digoxin increased by 47%. Coadministration should be monitored for ambrisentan toxicity. No a priori dose adjustment is required.

Description:

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No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

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No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

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No Interaction Expected

Capmatinib

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, which are not affected by capmatinib. 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). This does not affect capmatinib.

Description:

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No Interaction Expected

Capmatinib

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), which is not affected by capmatinib.

Description:

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Potential Weak Interaction

Capmatinib

Amitriptyline

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Amitriptyline is metabolised predominantly by CYP2D6 and CYP2C19, with a small proportion metabolised by CYPs 3A4, 1A2, and 2C9. Concentrations may increase due to inhibition of CYP1A2 by capmatinib. After coadministration with caffeine, a CYP1A2 substrate, the AUC of caffeine increased by 134%. Coadministration should be monitored for amitriptyline toxicity. No a priori dose adjustment is required.

Description:

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No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

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No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

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No Interaction Expected

Capmatinib

Amphotericin B

Quality of Evidence: Very Low

Summary:

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

Description:

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No Interaction Expected

Capmatinib

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, which is not affected by capmatinib. 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.

Description:

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No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

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No Interaction Expected

Capmatinib

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. No clinically significant interactions are expected based on changes in gastric pH caused by antacids.

Description:

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Potential Interaction

Capmatinib

Apixaban

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Apixaban is a substrate of P-gp and BCRP and is metabolised by CYP3A4 and to a lesser extent by CYPs 1A2, 2C8, 2C9, and 2C19. Apixaban concentrations may increase due to inhibition of CYP1A2, P-gp, and BCRP by capmatinib. After coadministration with digoxin, a P-gp substrate, the AUC of digoxin increased by 47%. After coadministration with rosuvastatin, a BCRP substrate, the AUC of rosuvastatin increased by 108%. After coadministration with caffeine, a CYP1A2 substrate, the AUC of caffeine increased by 134%. Coadministration should be avoided as apixaban toxicity may be increased. If coadministration is unavoidable, monitor closely for apixaban toxicity, anti-Xa levels, if available, and reduce the apixaban dose by 25%.

Description:

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Potential Weak Interaction

Capmatinib

Aprepitant

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Aprepitant is mainly metabolised by CYP3A4 and to a lesser extent by CYP1A2 and CYP2C19. Concentrations may increase due to inhibition of CYP1A2 by capmatinib. After coadministration with caffeine, a CYP1A2 substrate, the AUC of caffeine increased by 134%. Coadministration should be monitored for aprepitant toxicity. No a priori dose adjustment is required. During treatment, aprepitant is a moderate inhibitor of CYP3A4. However, after treatment, aprepitant is a weak inducer of CYP3A4, CYP2C9 and UGT. Thus, during short course treatment with aprepitant, concentrations of capmatinib may increase due to moderate inhibition of CYP3A by aprepitant. It is predicted that a moderate CYP3A inhibitor may increase capmatinib exposure by 30%. Coadministration should be monitored as toxicity of capmatinib may be increased. No a priori dose adjustment is required. If treatment-toxicities occur, a dose reduction should be considered to 300 mg twice daily. After treatment with aprepitant, concentrations of capmatinib may decrease due to weak induction of CYP3A by aprepitant, but this is unlikely to be clinically relevant.

Description:

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No Interaction Expected

Capmatinib

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, which are not affected by capmatinib.

Description:

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No Interaction Expected

Capmatinib

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)) and concentrations may increase due to inhibition of CYP1A2 by capmatinib. After coadministration of asenapine with fluvoxamine, a strong CYP1A2 inhibitor, exposure to asenapine was increased by 29%. Thus, no relevant interaction with capmatinib is expected.

Description:

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No Interaction Expected

Capmatinib

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. This is not affected by capmatinib.

Description:

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No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

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Potential Weak Interaction

Capmatinib

Atorvastatin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Atorvastatin is metabolised by CYP3A4 and is a substrate of P-gp and OATP1B1. Concentrations may increase due to inhibition of P-gp by capmatinib. After coadministration with digoxin, a P-gp substrate, the AUC of digoxin increased by 47%. Coadministration should be monitored for atorvastatin toxicity. No a priori dose adjustment is required.

Description:

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No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

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Potential Weak Interaction

Capmatinib

Azithromycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Azithromycin is mainly eliminated via biliary excretion; animal data suggest this may occur via P-gp and MRP2 and concentrations may increase due to inhibition of P-gp by capmatinib. After coadministration with digoxin, a P-gp substrate, the AUC of digoxin increased by 47%. Coadministration should be monitored for azithromycin toxicity. No a priori dose adjustment is required. Azithromycin is an inhibitor of P-gp, which does not affect capmatinib. Also, the clinical relevance of P-gp inhibition by azithromycin is unknown.

Description:

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No Interaction Expected

Capmatinib

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. This is not affected by capmatinib.

Description:

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No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

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No Interaction Expected

Capmatinib

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. This is not affected by capmatinib. In vitro data indicate that bendroflumethiazide inhibits these renal transporters but a clinically significant interaction is unlikely in the range of observed clinical concentrations.

Description:

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No Interaction Expected

Capmatinib

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. This is not affected by capmatinib.

Description:

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No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

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No Interaction Expected

Capmatinib

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, which does not affect capmatinib.

Description:

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No Interaction Expected

Capmatinib

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. This is unlikely to be affected by capmatinib.

Description:

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No Interaction Expected

Capmatinib

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. This is not affected by capmatinib.

Description:

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No Interaction Expected

Capmatinib

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. Concentrations of capmatinib may increase due to weak induction of CYP3A by bosentan, but this is unlikely to be clinically significant.

Description:

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Potential Weak Interaction

Capmatinib

Bromazepam

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Bromazepam undergoes oxidative biotransformation. Interaction studies indicate that CYP3A4 plays a minor role in bromazepam metabolism, but other cytochromes such as CYP2D6 or CYP1A2 may also play a role. Concentrations may increase due to inhibition of CYP1A2 by capmatinib. After coadministration with caffeine, a CYP1A2 substrate, the AUC of caffeine increased by 134%. Coadministration should be monitored for bromazepam toxicity. No a priori dose adjustment is required.

Description:

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No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

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No Interaction Expected

Capmatinib

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), which are not affected by capmatinib.

Description:

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No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

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No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

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No Interaction Expected

Capmatinib

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. This is not affected by capmatinib.

Description:

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No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

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No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

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No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

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Do Not Coadminister

Capmatinib

Carbamazepine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is contraindicated. Carbamazepine is primarily metabolised by CYP3A4 and to a lesser extent by CYP2C8, which are not affected by capmatinib. However, carbamazepine is an inducer of CYP2C8 (strong), CYP2C9 (strong), CYP3A4 (strong), CYP1A2 (weak), CYP2B6, UGT1A1, and P-gp (moderate). Concentrations of capmatinib may decrease due to strong induction of CYP3A by carbamazepine. After coadministration with rifampicin, a strong CYP3A inducer, capmatinib exposure decreased by 67%. Decreases in capmatinib exposure may decrease capmatinib anti-tumour activity. Coadministration is contraindicated.

Description:

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No Interaction Expected

Capmatinib

Carvedilol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Carvedilol undergoes glucuronidation via UGTs 1A1, 2B4, and 2B7, and additionally metabolism via CYP2D6 and to a lesser extent CYPs 2C9 and 1A2. Concentrations may increase due to inhibition of CYP1A2 by capmatinib, but this is unlikely to be clinically significant as CYP1A2 represents a minor pathway. Carvedilol is also an inhibitor of P-gp, which does not affect capmatinib.

Description:

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No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

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Potential Interaction

Capmatinib

Cefalexin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Cefalexin is predominantly eliminated unchanged renally by glomerular filtration and tubular secretion via OAT1 and MATE1. Concentrations may increase due to reversible MATE1/2 inhibition by capmatinib. This effect is only established in vitro but seemed very potent (Ki<<<Cmax). Coadministration should be avoided as cefalexin toxicity may be increased. If coadministration is unavoidable, monitor closely for cefalexin toxicity and consider cefalexin dose reductions.

Description:

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No Interaction Expected

Capmatinib

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. This is not affected by capmatinib.

Description:

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No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

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No Interaction Expected

Capmatinib

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, which is not affected by capmatinib. 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, which is not affected by capmatinib.

Description:

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No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

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No Interaction Expected

Capmatinib

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. This is not affected by capmatinib.

Description:

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No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

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No Interaction Expected

Capmatinib

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, which does not affect capmatinib.

Description:

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Potential Interaction

Capmatinib

Chloramphenicol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Chloramphenicol is predominantly glucuronidated, which is not affected by capmatinib. In vitro studies have shown that chloramphenicol can inhibit metabolism mediated by CYP3A4 (strong), CYP2C19 (strong), and CYP2D6 (weak). Concentrations of capmatinib may increase due to strong inhibition of CYP3A by chloramphenicol. After coadministration with itraconazole, a strong CYP3A4 inhibitor, exposure increased by 42% (no change Cmax). Monitor closely for capmatinib toxicities. If treatment-limiting toxicities occur, a dose reduction should be considered, e.g. from a daily dose of 800 mg (400 mg twice daily) to a daily dose of 500 mg (300 mg in the morning, 200 mg in the evening). 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

Capmatinib

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 metabolized by CYP3A4, which is not affected by capmatinib.

Description:

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No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

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Potential Weak Interaction

Capmatinib

Chlorpromazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Chlorpromazine is metabolised mainly by CYP2D6, but also by CYP1A2 and concentrations may increase due to inhibition of CYP1A2 by capmatinib. After coadministration with caffeine, a CYP1A2 substrate, the AUC of caffeine increased by 134%. Coadministration should be monitored for chlorpromazine toxicity. No a priori dose adjustment is required.

Description:

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No Interaction Expected

Capmatinib

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, and are not affected by capmatinib. 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.

Description:

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Potential Weak Interaction

Capmatinib

Ciclosporin (Cyclosporine)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Ciclosporin is a substrate of CYP3A4 and P-gp and concentrations may increase due to inhibition of P-gp by capmatinib. After coadministration with digoxin, a P-gp substrate, the AUC of digoxin increased by 47%. Coadministration should be monitored for ciclosporin toxicity and plasma concentrations. No a priori dose adjustment is required. Moreover, ciclosporin inhibits CYP3A4 and OATP1B1. Concentrations of capmatinib may increase due to weak inhibition of CYP3A by ciclosporin, but this is unlikely to be clinically significant.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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. In vitro data indicate that cimetidine inhibits OAT1 and OCT2 but at concentrations much higher than the observed clinical concentrations. Cimetidine is also a weak inhibitor of CYPs 3A4, 1A2, 2D6, and 2C19. Concentrations of capmatinib may increase due to weak inhibition of CYP3A by cimetidine, but this is unlikely to be clinically significant. Furthermore, no clinically significant interactions are expected based on changes in gastric pH caused by cimetidine.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib. It is also metabolised and partially cleared through the bile and intestine. Ciprofloxacin is also a weak to moderate inhibitor of CYP3A4 and a strong inhibitor of CYP1A2. This does not affect capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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%). This is not affected by capmatinib.

Description:

See summary

Potential Interaction

Capmatinib

Clarithromycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Clarithromycin is metabolised by CYP3A4 and is also an inhibitor of CYP3A4 (strong) and P-gp. Concentrations of capmatinib may increase due to strong inhibition of CYP3A by clarithromycin. After coadministration with itraconazole, a strong CYP3A4 inhibitor, exposure increased by 42% (no change Cmax). Monitor closely for capmatinib toxicities. If treatment-limiting toxicities occur, a dose reduction should be considered, e.g. from a daily dose of 800 mg (400 mg twice daily) to a daily dose of 500 mg (300 mg in the morning, 200 mg in the evening).

Description:

See summary

No Interaction Expected

Capmatinib

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. This is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

Potential Weak Interaction

Capmatinib

Clindamycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Clindamycin is metabolised by CYP3A4 and in vitro data suggest that it is a CYP3A4 inhibitor. Concentrations of capmatinib may increase due to inhibition of CYP3A by clindamycin. Coadministration should be monitored as toxicity of capmatinib may be increased. No a priori dose adjustment is required. If treatment-toxicities occur, a dose reduction should be considered to 300mg twice daily.

Description:

See summary

No Interaction Expected

Capmatinib

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

Capmatinib

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, which is not affected by capmatinib. In vitro data suggest that clofazimine is a CYP3A4 inhibitor. Concentrations of capmatinib may increase due to inhibition of CYP3A by clofazimine. Coadministration should be monitored as toxicity of capmatinib may be increased. No a priori dose adjustment is required. If treatment-toxicities occur, a dose reduction should be considered to 300mg twice daily.

Description:

See summary

No Interaction Expected

Capmatinib

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. This is not affected by capmatinib.

Description:

See summary

Potential Weak Interaction

Capmatinib

Clomipramine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Clomipramine is metabolised by CYPs 3A4, 1A2, and 2C19 to desmethylclomipramine, an active metabolite which has a higher activity than the parent drug. Desmethylclomipramine concentrations may increase due to inhibition of CYP1A2 by capmatinib. After coadministration with caffeine, a CYP1A2 substrate, the AUC of caffeine increased by 134%. Coadministration should be monitored for clomipramine toxicity. No a priori dose adjustment is required. In addition, clomipramine and desmethylclomipramine are metabolised by CYP2D6, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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), which is not affected by capmatinib. Clonidine is also a weak inhibitor of OCT2, which does not affect capmatinib.

Description:

See summary

Potential Interaction

Capmatinib

Clopidogrel

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Clopidogrel is a prodrug and is converted to its active metabolite mainly through CYP2C19 with CYPs 3A4, 2B6, and 1A2 playing a minor role. Concentrations of clopidogrel may increase and concentrations of its active metabolite may decrease due to inhibition of CYP1A2 by capmatinib. After coadministration with caffeine, a CYP1A2 substrate, the AUC of caffeine increased by 134%. Coadministration should be avoided as the efficacy of clopidogrel may be decreased due to less formation of the active metabolite. If coadministration is unavoidable, monitor closely for clopidogrel efficacy. Additionally, clopidogrel is an inhibitor of CYP2C8 (strong), CYP2B6 (weak) and in vitro of CYP2C9 at high concentrations. This does not affect capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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. This is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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. This is not affected by capmatinib.

Description:

See summary

Potential Interaction

Capmatinib

Clozapine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Clozapine is metabolized mainly by CYP1A2 and CYP3A4, and to a lesser extent by CYP2C19 and CYP2D6 and concentrations may increase due to inhibition of CYP1A2 by capmatinib. After coadministration with caffeine, a CYP1A2 substrate, the AUC of caffeine increased by 134%. Coadministration should be avoided as clozapine toxicity may be increased. If coadministration is unavoidable, monitor closely for clozapine toxicity and decrease the dose of clozapine in accordance with the label.

Description:

See summary

Potential Weak Interaction

Capmatinib

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, which is not affected by capmatinib. Morphine is further metabolised 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, which is not affected by capmatinib. However, the metabolite morphine is a substrate of P-gp and concentrations may increase due to inhibition of P-gp by capmatinib. After coadministration with digoxin, a P-gp substrate, the AUC of digoxin increased by 47%. Coadministration should be monitored for morphine toxicity. No a priori dose adjustment is required.

Description:

See summary

Potential Weak Interaction

Capmatinib

Colchicine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Colchicine is metabolised by CYP3A4 and is a substrate of P-gp. Concentrations may increase due to inhibition of P-gp by capmatinib. After coadministration with digoxin, a P-gp substrate, the AUC of digoxin increased by 47%. Coadministration should be monitored for colchicine toxicity. No a priori dose adjustment is required.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

Potential Interaction

Capmatinib

Dabigatran

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Dabigatran is transported via P-gp and is renally excreted and concentrations may increase due to inhibition of P-gp by capmatinib. After coadministration with digoxin, a P-gp substrate, the AUC of digoxin increased by 47%. Coadministration should be avoided as dabigatran toxicity may be increased. If coadministration is unavoidable, monitor closely for dabigatran toxicity and administer dabigatran 2 hours before capmatinib in fasted state to circumvent the intestinal P-gp interaction. Monitor ECT/dTT, if available.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which are not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

Potential Weak Interaction

Capmatinib

Dexamethasone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Dexamethasone has been described as a weak inducer of CYP3A4 and could possibly decrease capmatinib plasma concentrations. However, the clinical relevance of this interaction is not known and the induction of CYP3A4 by dexamethasone has not been established yet. Monitoring of capmatinib efficacy should be considered. Furthermore, dexamethasone is a substrate of CYP3A4, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

Potential Weak Interaction

Capmatinib

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), which is not affected by capmatinib. However, morphine is a substrate of P-gp and concentrations may increase due to inhibition of P-gp by capmatinib. After coadministration with digoxin, a P-gp substrate, the AUC of digoxin increased by 47%. Coadministration should be monitored for morphine toxicity. No a priori dose adjustment is required.

Description:

See summary

No Interaction Expected

Capmatinib

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. This is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which are not affected by capmatinib.

Description:

See summary

Potential Weak Interaction

Capmatinib

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 and concentrations may increase due to inhibition of P-gp by capmatinib. After coadministration with digoxin, a P-gp substrate, the AUC of digoxin increased by 47%. Coadministration should be monitored for digoxin toxicity and plasma concentrations, if available. No a priori dose adjustment is required.

Description:

See summary

No Interaction Expected

Capmatinib

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. This is not affected by capmatinib.

Description:

See summary

Potential Weak Interaction

Capmatinib

Diltiazem

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Diltiazem is metabolised by CYP3A4 and CYP2D6, which are not affected by capmatinib. Diltiazem is also an inhibitor of CYP3A4 (moderate) and P-gp. However, the clinical relevance of P-gp inhibition by diltiazem is unknown. Concentrations of capmatinib may increase due to moderate inhibition of CYP3A by diltiazem. It is predicted that a moderate CYP3A inhibitor may increase capmatinib exposure by 30%. Coadministration should be monitored as toxicity of capmatinib may be increased. No a priori dose adjustment is required. If treatment-toxicities occur, a dose reduction to 300 mg twice daily should be considered.

Description:

See summary

No Interaction Expected

Capmatinib

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. Concentrations may increase due to inhibition of CYP1A2 by capmatinib, but this is unlikely to be clinically significant as CYP1A2 represents a minor pathway. Moreover, diphenhydramine is a weak inhibitor of CYP2D6, which does not affect capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which are not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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. This is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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%). This is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

Dopamine

Quality of Evidence: Very Low

Summary:

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

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib. In addition, doxepin and nordoxepin are metabolised by CYP2D6, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

Doxycycline

Quality of Evidence: Very Low

Summary:

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

Description:

See summary

No Interaction Expected

Capmatinib

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, which are not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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 metabolized to a minor extent via CYP3A4, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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. Dulaglutide delays gastric emptying and could possibly decrease the absorption rate of concomitantly administered oral drugs. The clinical relevance of delayed absorption is considered to be limited.

Description:

See summary

Potential Interaction

Capmatinib

Duloxetine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Duloxetine is metabolised by CYP2D6 and CYP1A2 and concentrations may increase due to inhibition of CYP1A2 by capmatinib. After coadministration with caffeine, a CYP1A2 substrate, the AUC of caffeine increased by 134%. Coadministration should be avoided as duloxetine toxicity may be increased. If coadministration is unavoidable, monitor closely for duloxetine toxicity and decrease the dose of duloxetine in accordance with the label.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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 metabolized to dihydrodydrogesterone (possibly via CYP3A4), which is not affected by capmatinib.

Description:

See summary

Potential Weak Interaction

Capmatinib

Edoxaban

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Edoxaban is partially metabolised by CYP3A4 (<10%) and is transported via P-gp and concentrations may increase due to inhibition of P-gp by capmatinib. After coadministration with digoxin, a P-gp substrate, the AUC of digoxin increased by 47%. Coadministration should be monitored for edoxaban toxicity. No a priori dose adjustment is required.

Description:

See summary

Potential Interaction

Capmatinib

Eltrombopag

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Eltrombopag is metabolised by cleavage conjugation (via UGT1A1 and UGT1A3) and oxidation (via CYP1A2 and CYP2C8) and concentrations may increase due to inhibition of CYP1A2 by capmatinib. After coadministration with caffeine, a CYP1A2 substrate, the AUC of caffeine increased by 134%. Coadministration should be avoided as eltrombopag toxicity may be increased. If coadministration is unavoidable, monitor closely for eltrombopag toxicity and decrease the dose of eltrombopag in accordance with the label.

Description:

See summary

No Interaction Expected

Capmatinib

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) This is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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. This is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

Ertapenem

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ertapenem is mainly eliminated through the kidneys by glomerular filtration with tubular secretion playing a minor role. This is not affected by capmatinib.

Description:

See summary

Potential Weak Interaction

Capmatinib

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. Concentrations of capmatinib may increase due to moderate inhibition of CYP3A by clindamycin. Coadministration should be monitored as toxicity of capmatinib may be increased. No a priori dose adjustment is required. If treatment-toxicities occur, a dose reduction should be considered to 300mg twice daily. Erythromycin is a substrate of CYP3A4 and P-gp and concentrations may increase due to inhibition of P-gp by capmatinib. After coadministration with digoxin, a P-gp substrate, the AUC of digoxin increased by 47%. Coadministration should be monitored for erythromycin toxicity. No a priori dose adjustment is required.

Description:

See summary

No Interaction Expected

Capmatinib

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. This is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

Esomeprazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Esomeprazole is metabolised by CYP2C19 and CYP3A4, which are not affected by capmatinib. Esomeprazole is also an inhibitor of CYP2C19, which does not affect capmatinib. The bioavailability of capmatinib is pH-dependent and, thus, an increase in gastric pH by esomeprazole reduces its bioavailability. Coadministration of capmatinib and rabeprazole decreased the AUC of capmatinib by 25%, this is not considered to be clinically significant. A similar effect may occur with esomeprazole.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

Potential Weak Interaction

Capmatinib

Estradiol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Estradiol is metabolised by CYP3A4, CYP1A2, and is glucuronidated. Concentrations of estradiol may increase due to inhibition of CYP1A2 by capmatinib. After coadministration with caffeine, a CYP1A2 substrate, AUC of caffeine increased by 134%. Coadministration should be monitored on estradiol toxicity. No a priori dose adjustment is required.

Description:

See summary

No Interaction Expected

Capmatinib

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%), which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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). This is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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 metabolized by CYP3A4, which is not affected by capmatinib.

Description:

See summary

Potential Weak Interaction

Capmatinib

Everolimus (Immunosuppressant)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Everolimus is mainly metabolised by CYP3A4 and is a substrate of P-gp. Concentrations may increase due to inhibition of P-gp by capmatinib. After coadministration with digoxin, a P-gp substrate, the AUC of digoxin increased by 47%. Coadministration should be monitored for everolimus toxicity and plasma concentrations. No a priori dose adjustment is required.

Description:

See summary

No Interaction Expected

Capmatinib

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. 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

Capmatinib

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. This is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib. In vitro data suggest that fenofibric acid inhibits OAT3, which does not affect capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

Potential Weak Interaction

Capmatinib

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 of P-gp by capmatinib. After coadministration with digoxin, a P-gp substrate, the AUC of digoxin increased by 47%. Coadministration should be monitored for fexofenadine toxicity. No a priori dose adjustment is required.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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

Capmatinib

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. This is not affected by capmatinib.

Description:

See summary

Potential Interaction

Capmatinib

Flucloxacillin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Flucloxacillin is mainly renally eliminated partly by glomerular filtration and partly by active secretion via OAT1. This is not affected by capmatinib. Flucloxacillin is described as a CYP3A4 inducer. However, the mechanism and clinical relevance of this interaction is unknown. Concentrations of capmatinib may decrease due to moderate induction of CYP3A by flucloxacillin. It is predicted that a moderate CYP3A inducer may decrease capmatinib exposure by 44%. Decreases in capmatinib exposure may decrease capmatinib anti-tumour activity. If coadministration is unavoidable, consider doubling the capmatinib dose from 400 mg twice daily to 800 mg twice daily.

Description:

See summary

Potential Weak Interaction

Capmatinib

Fluconazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Fluconazole is cleared primarily by renal excretion and is also an inhibitor of CYPs 3A4 (moderate), 2C9 (moderate), and 2C19 (strong). Concentrations of capmatinib may increase due to moderate inhibition of CYP3A by fluconazole. It is predicted that a moderate CYP3A inhibitor may increase capmatinib exposure by 30%. Coadministration should be monitored as toxicity of capmatinib may be increased. No a priori dose adjustment is required. If treatment-toxicities occur, a dose reduction should be considered to 300 mg twice daily.

Description:

See summary

No Interaction Expected

Capmatinib

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 metabolized to 5-fluorouracil (5-FU). 5-FU is further metabolized by dihydropyrimidine dehydrogenase (DPD) to an inactive metabolite. Capmatinib does not interfere with this elimination pathway.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which are not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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. This is not affected by capmatinib. Fluoxetine is a strong inhibitor of CYP2D6 and CYP2C19, which do not affect capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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. This is unlikely to be affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib. Note: A clinically significant interaction is also unlikely with the topical use of fluticasone.

Description:

See summary

No Interaction Expected

Capmatinib

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%). This is not affected by capmatinib. Fluvastatin potentially inhibits CYP2C9, however, the clinical relevance of CYP2C9 inhibition is unknown.

Description:

See summary

Potential Interaction

Capmatinib

Fluvoxamine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Fluvoxamine is metabolised mainly by CYP2D6 and to a lesser extent by CYP1A2 and concentrations may increase due to inhibition of CYP1A2 by capmatinib. After coadministration with caffeine, a CYP1A2 substrate, the AUC of caffeine increased by 134%. Coadministration should be monitored for fluvoxamine toxicity. No a priori dose adjustment of fluvoxamine is required. Fluvoxamine is also an inhibitor of CYPs 1A2 (strong), 2C19 (strong), 3A4 (moderate), 2C9 (weak-moderate), and 2D6 (weak). Concentrations of capmatinib may increase due to moderate inhibition of CYP3A4 by fluvoxamine. It is predicted that a moderate CYP3A inhibitor may increase capmatinib exposure. Coadministration should be monitored as toxicity of capmatinib may be increased. No a priori dose adjustment is required. If treatment-toxicities occur, a dose reduction should be considered to 300mg twice daily.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

Formoterol

Quality of Evidence: Very Low

Summary:

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

Description:

See summary

Potential Weak Interaction

Capmatinib

Fosaprepitant

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Fosaprepitant is rapidly, almost completely, converted to the active metabolite aprepitant. Aprepitant is mainly metabolised by CYP3A4 and to a lesser extent by CYP1A2 and CYP2C19 and concentrations may increase due to inhibition of CYP1A2 by capmatinib. After coadministration with caffeine, a CYP1A2 substrate, the AUC of caffeine increased by 134%. Coadministration should be monitored for aprepitant toxicity. No a priori dose adjustment is required. During treatment, aprepitant is a moderate inhibitor of CYP3A4. However, after treatment aprepitant is a weak inducer of CYP3A4, CYP2C9, and UGT. Thus, during short course treatment with fosaprepitant, concentrations of capmatinib may increase due to moderate inhibition of CYP3A by aprepitant. It is predicted that a moderate CYP3A inhibitor may increase capmatinib exposure by 30%. Coadministration should be monitored as toxicity of capmatinib may be increased. No a priori dose adjustment is required. If treatment-toxicities occur, a dose reduction should be considered to 300 mg twice daily. After treatment with fosaprepitant, concentrations of capmatinib may decrease due to weak induction of CYP3A by aprepitant, but this is unlikely to be clinically significant.

Description:

See summary

Do Not Coadminister

Capmatinib

Fosphenytoin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is contraindicated. Fosphenytoin is rapidly converted to the active metabolite phenytoin. Phenytoin is mainly metabolised by CYP2C9 and to a lesser extent by CYP2C19, which are not affected by capmatinib. Phenytoin is a potent inducer of CYP3A4, UGT, and P-gp. Concentrations of capmatinib may decrease due to strong induction of CYP3A by fosphenytoin. Decreases in capmatinib exposure may decrease capmatinib anti-tumour activity. After coadministration with rifampicin, a strong CYP3A inducer, capmatinib exposure decreased by 67%. A similar effect may occur with fosphenytoin, therefore coadministration is contraindicated.

Description:

See summary

No Interaction Expected

Capmatinib

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). This is not affected by capmatinib. A large proportion of furosemide is also eliminated unchanged renally (via OATs). OAT1/3 are the major transporters of loop and thiazide diuretics and are not affected by capmatinib. 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, which do not affect capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib. Gemfibrozil is 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. This does not affect capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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 metabolized by CYP3A4 and to a lesser extent by CYP2C9 and CYP2C19. This is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which are not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which are not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

Potential Weak Interaction

Capmatinib

Granisetron

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Granisetron is metabolised by CYP3A4 and is a substrate of P-gp. Concentrations may increase due to inhibition of P-gp by capmatinib. After coadministration with digoxin, a P-gp substrate, the AUC of digoxin increased by 47%. Coadministration should be monitored for granisetron toxicity. No a priori dose adjustment is required.

Description:

See summary

Do Not Coadminister

Capmatinib

Grapefruit juice

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is contraindicated. Grapefruit juice is known to inhibit CYP3A4 enzymes. Concentrations of capmatinib may increase due to strong inhibition of CYP3A by grapefruit juice. After coadministration with itraconazole, a strong CYP3A4 inhibitor, exposure increased by 42% (no change Cmax). A similar effect may occur with grapefruit juice, therefore coadministration is contraindicated.

Description:

See summary

No Interaction Expected

Capmatinib

Green tea

Quality of Evidence: Very Low

Summary:

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

Description:

See summary

Potential Interaction

Capmatinib

Griseofulvin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Less than 1% of a griseofulvin dose is excreted unchanged via the kidneys. Griseofulvin is also a liver microsomal enzyme inducer and may lower plasma levels, and therefore reduce the efficacy of concomitantly administered medicinal products that are metabolised by CYPs, such as capmatinib. Decreases in capmatinib exposure may decrease capmatinib anti-tumour activity, therefore coadministration with griseofulvin should be approached with caution.

Description:

See summary

No Interaction Expected

Capmatinib

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). This is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which are not affected by capmatinib. In vitro studies have suggested that hydralazine is a mixed enzyme inhibitor, which may weakly inhibit CYP3A4 and CYP2D6. Concentrations of capmatinib may increase due to weak inhibition of CYP3A by hydralazine, but this is unlikely to be clinically significant.

Description:

See summary

No Interaction Expected

Capmatinib

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 and are not affected by capmatinib. 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.

Description:

See summary

No Interaction Expected

Capmatinib

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. This is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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. This is not affected by capmatinib.

Description:

See summary

Potential Weak Interaction

Capmatinib

Ibandronic acid

Quality of Evidence: Very Low

Summary:

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

Description:

See summary

No Interaction Expected

Capmatinib

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. This is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which are not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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. This is not affected by capmatinib.

Description:

See summary

Potential Weak Interaction

Capmatinib

Imipramine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Imipramine is metabolised by CYPs 3A4, 2C19, and 1A2 to desipramine and concentrations may increase due to inhibition of CYP1A2 by capmatinib. After coadministration with caffeine, a CYP1A2 substrate, the AUC of caffeine increased by 134%. Coadministration should be monitored for imipramine toxicity. No a priori dose adjustment is required. Imipramine and desipramine are both metabolised by CYP2D6, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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 and are not affected by capmatinib. 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.

Description:

See summary

No Interaction Expected

Capmatinib

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

Capmatinib

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

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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), which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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

Capmatinib

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. This is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

Potential Interaction

Capmatinib

Itraconazole

Quality of Evidence: Low

Summary:

Coadministration has been studied and should be approached with caution. Itraconazole is primarily metabolised by CYP3A4 and is also an inhibitor of CYP3A4 (strong), CYP2C9 (weak), P-gp, and BCRP. Concentrations of capmatinib will increase due to strong inhibition of CYP3A by itraconazole. In healthy subjects (n=23) coadministration of capmatinib (400 mg single dose, day 6) and itraconazole (200 mg once daily, days 1-9), increased capmatinib exposure by 42% (no change Cmax). Monitor closely for capmatinib toxicities. If treatment-limiting toxicities occur, a dose reduction should be considered, e.g., from a daily dose of 800 mg (400 mg twice daily) to a daily dose of 500 mg (300 mg in the morning, 200 mg in the evening).

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

Potential Interaction

Capmatinib

Ketoconazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Ketoconazole is a substrate for CYP3A4. Moreover, ketoconazole is an inhibitor of CYP3A4 (strong) and P-gp. Concentrations of capmatinib may increase due to strong inhibition of CYP3A by ketoconazole. After coadministration with itraconazole, a strong CYP3A4 inhibitor, exposure increased by 42% (no change Cmax). Monitor closely for capmatinib toxicities. If treatment-limiting toxicities occur, a dose reduction should be considered, e.g., from a daily dose of 800 mg (400 mg twice daily) to a daily dose of 500 mg (300 mg in the morning, 200 mg in the evening).

Description:

See summary

No Interaction Expected

Capmatinib

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), which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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. This is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which are not affected by capmatinib. The bioavailability of capmatinib is pH-dependent and, thus, an increase in gastric pH by lansoprazole reduces its bioavailability. Coadministration of capmatinib and rabeprazole decreased the AUC of capmatinib by 25%, this is not considered to be clinically significant. A similar effect may occur with lansoprazole.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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. This is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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) This is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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 metabolized by CYP3A4 and is glucuronidated to a minor extent. This is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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 metabolized by CYP3A4 and is glucuronidated to a minor extent. This is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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. This is not affected by capmatinib.

Description:

See summary

Potential Weak Interaction

Capmatinib

Lidocaine (Lignocaine)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. CYP1A2 is the predominant enzyme involved in lidocaine metabolism in the range of therapeutic concentrations with a minor contribution from CYP3A4. Concentrations may increase due to inhibition of CYP1A2 by capmatinib. After coadministration with caffeine, a CYP1A2 substrate, the AUC of caffeine increased by 134%. Coadministration should be monitored for lidocaine toxicity. No a priori dose adjustment is required.

Description:

See summary

Potential Weak Interaction

Capmatinib

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, this is not affected by capmatinib. However, linagliptin is also a substrate for P-gp and concentrations may increase due to inhibition of P-gp by capmatinib. After coadministration with digoxin, a P-gp substrate, the AUC of digoxin increased by 47%. Coadministration should be monitored for linagliptin toxicity. No a priori dose adjustment is required. Moreover, linagliptin and is a weak inhibitor of CYP3A4. Concentrations of capmatinib may increase due to weak inhibition of CYP3A by linagliptin, but this is unlikely to be clinically significant.

Description:

See summary

No Interaction Expected

Capmatinib

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. Capmatinib is unlikely to affect this unspecified metabolic pathway.

Description:

See summary

No Interaction Expected

Capmatinib

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, which are not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

Lithium

Quality of Evidence: Very Low

Summary:

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

Description:

See summary

No Interaction Expected

Capmatinib

Live vaccines

Quality of Evidence: Very Low

Summary:

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

Description:

See summary

Potential Weak Interaction

Capmatinib

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, and is a substrate of P-gp. Concentrations may increase due to inhibition of P-gp by capmatinib. After coadministration with digoxin, a P-gp substrate, the AUC of digoxin increased by 47%. Coadministration should be monitored for loperamide toxicity. No a priori dose adjustment is required.

Description:

See summary

No Interaction Expected

Capmatinib

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, which are not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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. This is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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. This is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

Medroxyprogesterone (non-depot)

Quality of Evidence: Very Low

Summary:

Description:

See summary

No Interaction Expected

Capmatinib

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. This is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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. This is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

Potential Interaction

Capmatinib

Metamizole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution when metamizole is used for longer than one week. 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%). Metamizole is an inducer of CYP3A4 and concentrations of capmatinib may decrease. However, this effect is only considered relevant if metamizole is used longer than one week. It is predicted that a moderate CYP3A inducer may decrease capmatinib exposure by 44%. Decreases in capmatinib exposure may decrease capmatinib anti-tumour activity. Thus, when metamizole is used longer than one week, avoid coadministration and consider doubling the capmatinib dose from 400 mg twice daily to 800 mg twice daily.

Description:

See summary

Potential Interaction

Capmatinib

Metformin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Metformin is mainly eliminated unchanged in the urine and is substrate for OCT1, OCT2, OCT3, MATE1, and MATE2K and concentrations may increase due to reversible MATE1/2 inhibition by capmatinib. This effect is only established in vitro, but seemed very potent (Ki<<<Cmax). Monitor closely for metformin toxicity and consider dose reductions.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

Methylphenidate

Quality of Evidence: Very Low

Summary:

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

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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), which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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 and are not affected by capmatinib. 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.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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. 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). Thus, no relevant interaction with capmatinib is expected.

Description:

See summary

Potential Weak Interaction

Capmatinib

Mexiletine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Mexiletine is metabolised mainly by CYP2D6 and to a lesser extent CYP1A2. Concentrations may increase due to inhibition of CYP1A2 by capmatinib. After coadministration with caffeine, a CYP1A2 substrate, the AUC of caffeine increased by 134%. Coadministration should be monitored for mexiletine toxicity. No a priori dose adjustment is required.

Description:

See summary

Potential Interaction

Capmatinib

Mianserin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Mianserin is metabolised by CYPs 2D6 and 1A2, and to a lesser extent by CYP3A4. Concentrations may increase due to inhibition of CYP1A2 by capmatinib. After coadministration with caffeine, a CYP1A2 substrate, the AUC of caffeine increased by 134%. Coadministration should be avoided as mianserin toxicity may be increased. If coadministration is unavoidable, monitor closely for mianserin toxicity and decrease the dose of mianserin in accordance with the label.

Description:

See summary

Potential Interaction

Capmatinib

Miconazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Miconazole is extensively metabolised by the liver. Moreover, miconazole is an inhibitor of CYP2C9 (moderate) and CYP3A4 (strong). Concentrations of capmatinib may increase due to strong inhibition of CYP3A by miconazole. After coadministration with itraconazole, a strong CYP3A4 inhibitor, exposure increased by 42% (no change Cmax). Monitor closely for capmatinib toxicities. If treatment-limiting toxicities occur, a dose reduction should be considered, e.g., from a daily dose of 800 mg (400 mg twice daily) to a daily dose of 500 mg (300 mg in the morning, 200 mg in the evening). Note: after dermal application miconazole is only minimally absorbed. Therefore, no clinically relevant interaction is expected.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

Midazolam (parenteral)

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, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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%). This is not affected by capmatinib.

Description:

See summary

Potential Interaction

Capmatinib

Mirtazapine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Mirtazapine is metabolised to 8-hydroxymirtazapine by CYP2D6 and CYP1A2, and to N-desmethylmirtazapine mainly by CYP3A4 and concentrations may increase due to inhibition of CYP1A2 by capmatinib. After coadministration with caffeine, a CYP1A2 substrate, AUC of caffeine increased by 134%. Coadministration should be avoided as mirtazapine toxicity may be increased. If coadministration is unavoidable, monitor closely for mirtazapine toxicity and decrease the dose of mirtazapine in accordance with the label.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib. Note: No clinically relevant interaction is expected with the topical use of mometasone.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

Potential Weak Interaction

Capmatinib

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). This is not affected by capmatinib. However, morphine is a substrate of P-gp and concentrations may increase due to inhibition of P-gp by capmatinib. After coadministration with digoxin, a P-gp substrate, the AUC of digoxin increased by 47%. Coadministration should be monitored for morphine toxicity. No a priori dose adjustment is required.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which are not affected by capmatinib. The active metabolite of mycophenolate, mycophenolic acid, is an inhibitor of OAT1/OAT3, which do not affect capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

Nadroparin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nadroparin is excreted renally by a nonsaturable mechanism, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

Potential Weak Interaction

Capmatinib

Naproxen

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Naproxen is mainly glucuronidated by UGT2B7 (major) and demethylated to desmethylnaproxen by CYP2C9 (major) and CYP1A2. Concentrations may increase due to inhibition of CYP1A2 by capmatinib. After coadministration with caffeine, a CYP1A2 substrate, the AUC of caffeine increased by 134%. Coadministration should be monitored for naproxen toxicity. No a priori dose adjustment is required.

Description:

See summary

No Interaction Expected

Capmatinib

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%). This is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

Potential Interaction

Capmatinib

Nefazodone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Nefazodone is metabolised mainly by CYP3A4 and is also a strong inhibitor of CYP3A4. Concentrations of capmatinib may increase due to strong inhibition of CYP3A by nefazodone . After coadministration with itraconazole, a strong CYP3A4 inhibitor, exposure increased by 42% (no change Cmax). Monitor closely for capmatinib toxicities. If treatment-limiting toxicities occur, a dose reduction should be considered, e.g., from a daily dose of 800 mg (400 mg twice daily) to a daily dose of 500 mg (300 mg in the morning, 200 mg in the evening).

Description:

See summary

No Interaction Expected

Capmatinib

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, which are not affected by capmatinib. Moreover, nicardipine is a weak inhibitor of CYP3A4. Concentrations of capmatinib may increase due to weak inhibition of CYP3A by nicardipine, but this is unlikely to be clinically significant.

Description:

See summary

No Interaction Expected

Capmatinib

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, which are not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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%). This is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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 metabolized to norgestrel (possibly by CYP3A4), which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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. This is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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 metabolized via CYP450. This is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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 metabolised by CYP3A4 and is glucuronidated to a minor extent. This is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

Potential Weak Interaction

Capmatinib

Olanzapine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Olanzapine is metabolised mainly by CYP1A2 (major) and CYP2D6, but also by glucuronidation (UGT1A4) and concentrations may increase due to inhibition of CYP1A2 by capmatinib. After coadministration with caffeine, a CYP1A2 substrate, the AUC of caffeine increased by 134%. Coadministration should be monitored for olanzapine toxicity. No a priori dose adjustment is required.

Description:

See summary

No Interaction Expected

Capmatinib

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. This is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which are not affected by capmatinib. Omeprazole is also an inducer of CYP1A2 and an inhibitor of CYP2C19, which do not affect capmatinib. The bioavailability of capmatinib is pH-dependent and, thus, an increase in gastric pH by omeprazole reduces its bioavailability. Coadministration of capmatinib and rabeprazole decreased the AUC of capmatinib by 25%, this is not considered to be clinically significant. A similar effect may occur with omeprazole.

Description:

See summary

Potential Weak Interaction

Capmatinib

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. Additionally, ondansetron is a substrate of P-gp. Concentrations may increase due to inhibition of P-gp and CYP1A2 by capmatinib. After coadministration with digoxin, a P-gp substrate, the AUC of digoxin increased by 47%. After coadministration with caffeine, a CYP1A2 substrate, the AUC of caffeine increased by 134%. Coadministration should be monitored for ondansetron toxicity. No a priori dose adjustment is required.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

Potential Interaction

Capmatinib

Oxcarbazepine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Oxcarbazepine is extensively metabolised to the active metabolite monohydroxyderivate (MHD) through cytosolic enzymes. Both oxcarbazepine and MHD are inducers of CYP3A4 (moderate) and CYP3A5 and are inhibitors of CYP2C19. Concentrations of capmatinib may decrease due to moderate induction of CYP3A by oxcarbazepine. It is predicted that a moderate CYP3A inducer may decrease capmatinib exposure by 44%. Decreases in capmatinib exposure may decrease capmatinib anti-tumour activity. Avoid coadministration or consider doubling the capmatinib dose from 400 mg twice daily to 800 mg twice daily.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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. This is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which are not affected by capmatinib.

Description:

See summary

Potential Weak Interaction

Capmatinib

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. Palonosetron is also a substrate of P-gp. Concentrations may increase due to inhibition of P-gp and CYP1A2 by capmatinib. After coadministration with digoxin, a P-gp substrate, the AUC of digoxin increased by 47%. After coadministration with caffeine, a CYP1A2 substrate, the AUC of caffeine increased by 134%. Coadministration should be monitored for palonosetron toxicity. No a priori dose adjustment is required.

Description:

See summary

No Interaction Expected

Capmatinib

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. This is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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. This is not affected by capmatinib. The bioavailability of capmatinib is pH-dependent and, thus, an increase in gastric pH by pantoprazole reduces its bioavailability. Coadministration of capmatinib and rabeprazole decreased the AUC of capmatinib by 25%, this is not considered to be clinically significant. A similar effect may occur with pantoprazole.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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). This is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib. Moreover, paroxetine is an inhibitor of CYP2D6 (strong) and CYP2C9, which does not affect capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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

Capmatinib

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), which is not affected by capmatinib.

Description:

See summary

Potential Weak Interaction

Capmatinib

Perazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Perazine is mainly metabolised by CYPs 1A2, 3A4, and 2C19, and to a lesser extent by CYPs 2C9, 2D6, and 2E1, with oxidation via FMO3. Concentrations may increase due to inhibition of CYP1A2 by capmatinib. After coadministration with caffeine, a CYP1A2 substrate, the AUC of caffeine increased by 134%. Coadministration should be monitored for perazine toxicity. No a priori dose adjustment is required.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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. This is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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. This is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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.

Description:

See summary

Do Not Coadminister

Capmatinib

Phenobarbital (Phenobarbitone)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is contraindicated. Phenobarbital is metabolised by CYP2C19 and CYP2C9 (major pathway) and to a lesser extent by CYP2E1. This is not affected by capmatinib. Phenobarbital is a strong inducer of CYP3A4, CYP2C9, CYP2C8, and UGTs. Concentrations of capmatinib may decrease due to strong induction of CYP3A by phenobarbital. Decreases in capmatinib exposure may decrease capmatinib anti-tumour activity. After coadministration with rifampicin, a strong CYP3A inducer, capmatinib exposure decreased by 67%. A similar effect may occur with phenobarbital, therefore coadministration is contraindicated.

Description:

See summary

No Interaction Expected

Capmatinib

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, which are not affected by capmatinib.

Description:

See summary

Do Not Coadminister

Capmatinib

Phenytoin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is contraindicated. Phenytoin is mainly metabolised by CYP2C9 and to a lesser extent by CYP2C19, which are not affected by capmatinib. Phenytoin is a strong inducer of CYP3A4, UGT, and P-gp. Concentrations of capmatinib may decrease due to strong induction of CYP3A by phenytoin. Decreases in capmatinib exposure may decrease capmatinib anti-tumour activity. After coadministration with rifampicin, a strong CYP3A inducer, capmatinib exposure decreased by 67%. A similar effect may occur with phenytoin, therefore coadministration is contraindicated.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

Potential Weak Interaction

Capmatinib

Pimozide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Pimozide is mainly metabolised by CYP3A4 and CYP2D6 and to a lesser extent by CYP1A2. Concentrations may increase due to inhibition of CYP1A2 by capmatinib. After coadministration with caffeine, a CYP1A2 substrate, the AUC of caffeine increased by 134%. Coadministration should be monitored for pimozide toxicity. No a priori dose adjustment is required.

Description:

See summary

No Interaction Expected

Capmatinib

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. This is not affected by capmatinib.

Description:

See summary

Potential Weak Interaction

Capmatinib

Pioglitazone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Pioglitazone is metabolised mainly by CYP2C8 and to a lesser extent by CYPs 3A4, 1A2, and 2C9 and concentrations may increase due to inhibition of CYP1A2 by capmatinib. After coadministration with caffeine, a CYP1A2 substrate, the AUC of caffeine increased by 134%. Coadministration should be monitored for pioglitazone toxicity. No a priori dose adjustment is required

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

Pitavastatin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pitavastatin is metabolised by UGTs 1A3 and 2B7 with minimal metabolism by CYPs 2C9 and 2C8. This is not affected by capmatinib. Pitavastatin is a substrate of OATP1B1, which is not affected by capmatinib.

Description:

See summary

Potential Interaction

Capmatinib

Posaconazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Posaconazole is primarily metabolized by UGTs and is a substrate for P-gp. Concentrations may increase due to inhibition of P-gp by capmatinib. After coadministration with digoxin, a P-gp substrate, the AUC of digoxin increased by 47%. Coadministration should be monitored for posaconazole toxicity. No a priori dose adjustment of posaconazole is required. Moreover, posaconazole is a strong inhibitor of CYP3A4. Concentrations of capmatinib may increase due to strong inhibition of CYP3A by posaconazole. After coadministration with itraconazole, a strong CYP3A4 inhibitor, exposure increased by 42% (no change Cmax). Monitor closely for capmatinib toxicities. If treatment-limiting toxicities occur, a dose reduction should be considered, e.g., from a daily dose of 800 mg (400 mg twice daily) to a daily dose of 500 mg (300 mg in the morning, 200 mg in the evening).

Description:

See summary

No Interaction Expected

Capmatinib

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. This is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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. This is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which are not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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). This is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

Prochlorperazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Prochlorperazine is metabolised by CYP2D6 and CYP2C19, which are not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

Potential Weak Interaction

Capmatinib

Propafenone

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Propafenone is metabolised mainly by CYP2D6 and to a lesser extent by CYP1A2 and CYP3A4. Concentrations may increase due to inhibition of CYP1A2 by capmatinib. After coadministration with caffeine, a CYP1A2 substrate, the AUC of caffeine increased by 134%. Coadministration should be monitored for propafenone toxicity. No a priori dose adjustment is required.

Description:

See summary

Potential Interaction

Capmatinib

Propranolol

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. 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). Concentrations may increase due to inhibition of CYP1A2 by capmatinib. After coadministration with caffeine, a CYP1A2 substrate, the AUC of caffeine increased by 134%. Coadministration should be avoided as propranolol toxicity may be increased. If coadministration is unavoidable, monitor closely for propranolol toxicity and decrease the dose of propranolol in accordance with the label. Carvedilol is also an inhibitor of P-gp, which does not affect capmatinib. Also, the clinical relevance of P-gp inhibition by carvedilol is unknown.

Description:

See summary

Potential Weak Interaction

Capmatinib

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. Additionally, prucalopride is a substrate of P-gp and concentrations may increase due to inhibition of P-gp by capmatinib. After coadministration with digoxin, a P-gp substrate, the AUC of digoxin increased by 47%. Coadministration should be monitored for prucalopride toxicity. No a priori dose adjustment is required.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

Potential Weak Interaction

Capmatinib

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. This is not affected by capmatinib. No a priori dose adjustment is required. Quinidine is an inhibitor of CYP2D6 (strong), CYP3A4 (weak), and P-gp (moderate). Concentrations of capmatinib may increase due to weak inhibition of CYP3A by quinidine, but this is unlikely to be clinically significant. Quinidine is a substrate of P-gp and concentrations may increase due to inhibition of P-gp by capmatinib. After coadministration with digoxin, a P-gp substrate, the AUC of digoxin increased by 47%. Coadministration should be monitored for quinidine toxicity.

Description:

See summary

No Interaction Expected

Capmatinib

Rabeprazole

Quality of Evidence: Very Low

Summary:

Coadministration has been studied and a clinically significant interaction is unlikely. Rabeprazole is mainly metabolised via non-enzymatic reduction and to a lesser extent by CYP2C19 and CYP3A4, which is not affected by capmatinib. The bioavailability of capmatinib is pH-dependent and, thus, an increase in gastric pH by rabeprazole reduces its bioavailability. In healthy subjects (n=20) coadministration of capmatinib (600mg single dose day 1 and 10) and rabeprazole (20mg once daily, days 7-10) decreased the AUC of capmatinib by 25%. This is not considered to be clinically significant.

Description:

See summary

No Interaction Expected

Capmatinib

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. This is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib. Furthermore, no clinically significant interactions are expected based on changes in gastric pH caused by ranitidine.

Description:

See summary

Potential Weak Interaction

Capmatinib

Ranolazine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Ranolazine is primarily metabolised by CYP3A4 and to a lesser extent by CYP2D6, which are not affected by capmatinib. Ranolazine is a substrate of P-gp. Moreover, ranolazine is a weak inhibitor of P-gp, CYP3A4, and CYP2D6. Concentrations may increase due to inhibition of P-gp by capmatinib. After coadministration with digoxin, a P-gp substrate, the AUC of digoxin increased by 47%. Coadministration should be monitored for ranolazine toxicity. No a priori dose adjustment is required. Concentrations of capmatinib may increase due to weak inhibition of CYP3A by ranolazine, but this is unlikely to be clinically significant.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib. In vitro data indicate reboxetine to be a weak inhibitor of CYP3A4 but in vivo data showed no inhibitory effect on CYP3A4.

Description:

See summary

No Interaction Expected

Capmatinib

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. This is not affected by and does not affect capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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. This is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

Riboflavin (Vitamin B2)

Quality of Evidence: Very Low

Summary:

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

Description:

See summary

Do Not Coadminister

Capmatinib

Rifabutin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is contraindicated. Rifabutin is metabolised by CYP3A4 and via deacetylation. This is not affected by capmatinib. Rifabutin is also a strong CYP3A4 and P-gp inducer. Concentrations of capmatinib may decrease due to strong induction of CYP3A by rifabutin. Decreases in capmatinib exposure may decrease capmatinib anti-tumour activity. After coadministration with rifampicin, a strong CYP3A inducer, capmatinib exposure decreased by 67%. A similar effect may occur with rifabutin, therefore coadministration is contraindicated.

Description:

See summary

Do Not Coadminister

Capmatinib

Rifampicin

Quality of Evidence: Low

Summary:

Coadministration has been studied and is contraindicated. Rifampicin is metabolised via deacetylation and is also a strong CYP3A4 and P-gp inducer. Concentrations of capmatinib will decrease due to strong induction of CYP3A by rifampicin. Decreases in capmatinib exposure may decrease capmatinib anti-tumour activity. In healthy subjects (n=24) coadministration of capmatinib (400 mg single dose, day 6) and rifampicin (600 mg once daily, days 1-9), decreased capmatinib exposure by 67%. Coadministration is contraindicated.

Description:

See summary

Do Not Coadminister

Capmatinib

Rifapentine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is contraindicated. Rifapentine is metabolised via deacetylation and is also a strong CYP3A4, CYP2C8, and P-gp inducer. Concentrations of capmatinib may decrease due to strong induction of CYP3A by rifapentine. Decreases in capmatinib exposure may decrease capmatinib anti-tumour activity. After coadministration with rifampicin, a strong CYP3A inducer, capmatinib exposure decreased by 67%. A similar effect may occur with rifapentine, therefore coadministration is contraindicated.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

Potential Weak Interaction

Capmatinib

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, which are not affected by capmatinib. Furthermore, risperidone is a substrate of P-gp and concentrations may increase due to inhibition of P-gp by capmatinib. After coadministration with digoxin, a P-gp substrate, the AUC of digoxin increased by 47%. Coadministration should be monitored for risperidone toxicity. No a priori dose adjustment is required.

Description:

See summary

Do Not Coadminister

Capmatinib

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. Moreover, rivaroxaban is substrate for P-gp and BCRP and concentrations may increase due to inhibition of P-gp and BCRP by capmatinib. After coadministration with digoxin, a P-gp substrate, the AUC of digoxin increased by 47%. After coadministration with rosuvastatin, a BCRP substrate, the AUC of rosuvastatin increased by 108%. Similar effects may occur after coadministration with rivaroxaban. Therefore, coadministration is contra-indicated as rivaroxaban toxicity increases with increased exposure.

Description:

See summary

No Interaction Expected

Capmatinib

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. This is not affected by capmatinib.

Description:

See summary

Potential Interaction

Capmatinib

Rosuvastatin

Quality of Evidence: Very Low

Summary:

Coadministration has been studied and should be approached with caution. Rosuvastatin is largely excreted unchanged via the faeces via OATP1B1 and is substrate for BCRP. Concentrations will increase due to inhibition of BCRP by capmatinib. In non-small cell lung cancer patients (n=32), coadministration of rosuvastatin (10mg single dose, days 1 and 22) and capmatinib (400mg twice daily, days 11-32), increased the AUC of rosuvastatin by 108%. Coadministration should be avoided as rosuvastatin toxicity may be increased. If coadministration is unavoidable, monitor closely for rosuvastatin toxicity and decrease the dose in accordance with the label.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib. The systemic exposure of salmeterol is low.

Description:

See summary

Potential Weak Interaction

Capmatinib

Saxagliptin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Saxagliptin is mainly metabolised by CYP3A4 and is a substrate of P-gp and concentrations may increase due to inhibition of P-gp by capmatinib. After coadministration with digoxin, a P-gp substrate, the AUC of digoxin increased by 47%. Coadministration should be monitored for saxagliptin toxicity. No a priori dose adjustment is required.

Description:

See summary

No Interaction Expected

Capmatinib

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

Capmatinib

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, which are not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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. This is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which are not affected by capmatinib.

Description:

See summary

Potential Interaction

Capmatinib

Simvastatin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Simvastatin is metabolised by CYP3A4, which is not affected by capmatinib. Moreover, simvastatin is a substrate for BCRP, and the active metabolite is a substrate of OATP1B1. Concentrations of simvastatin may increase due to inhibition of BCRP by capmatinib. After coadministration with rosuvastatin, a BCRP substrate, the AUC of rosuvastatin increased by 108%. Coadministration should be avoided as simvastatin toxicity may be increased. If coadministration is unavoidable, monitor closely for simvastatin toxicity and decrease the dose in accordance with the label.

Description:

See summary

Potential Weak Interaction

Capmatinib

Sirolimus

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Sirolimus is metabolised by CYP3A4 and is substrate of P-gp and concentrations may increase due to inhibition of P-gp by capmatinib. After coadministration with digoxin, a P-gp substrate, the AUC of digoxin increased by 47%. Coadministration should be monitored for sirolimus toxicity and plasma concentrations. No a priori dose adjustment is required.

Description:

See summary

Potential Weak Interaction

Capmatinib

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 (active secretion by OAT3, OATP4C1, and P-gp) and metabolism by CYP3A4 represents a minor metabolic pathway. Concentrations may increase due to inhibition of P-gp by capmatinib. After coadministration with digoxin, a P-gp substrate, the AUC of digoxin increased by 47%. Coadministration should be monitored for sitagliptin toxicity. No a priori dose adjustment is required.

Description:

See summary

No Interaction Expected

Capmatinib

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. This is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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

Description:

See summary

Do Not Coadminister

Capmatinib

St John's Wort

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is contraindicated. St John’s wort is a P-gp and CYP3A4 inducer. Concentrations of capmatinib may decrease due to strong induction of CYP3A by St John’s Wort. Decreases in capmatinib exposure may decrease capmatinib anti-tumour activity. After coadministration with rifampicin, a strong CYP3A inducer, capmatinib exposure decreased by 67%. A similar effect may occur with St John’s Wort, therefore coadministration is contraindicated.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib. 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. Concentrations of capmatinib may increase due to inhibition of CYP3A by tacrolimus, but this is unlikely to be clinically significant.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which are not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

Potential Interaction

Capmatinib

Telithromycin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Telithromycin is metabolised by CYP3A4 (50%) with the remaining 50% metabolised via non-CYP mediated pathways. This is not affected by capmatinib. Telithromycin is also an inhibitor of CYP3A4 (strong), and P-gp. The clinical relevance of P-gp inhibition is unknown. Concentrations of capmatinib may increase due to strong inhibition of CYP3A by telithromycin. After coadministration with itraconazole, a strong CYP3A4 inhibitor, exposure increased by 42% (no change Cmax). Monitor closely for capmatinib toxicities. If treatment-limiting toxicities occur, a dose reduction should be considered e.g., from a daily dose of 800 mg (400 mg twice daily) to a daily dose of 500 mg (300 mg in the morning, 200 mg in the evening).

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

Potential Interaction

Capmatinib

Terbinafine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Terbinafine is metabolised by CYPs 1A2, 2C9, 3A4, and to a lesser extent CYP2C8 and CYP2C19. Concentrations of terbinafine may increase due to inhibition of CYP1A2 by capmatinib. After coadministration with caffeine, a CYP1A2 substrate, AUC of caffeine increased by 134%. Coadministration should be avoided as terbinafine toxicity may be increased. If coadministration is unavoidable, monitor closely for terbinafine toxicity and decrease the dose of terbinafine in accordance with the label. Terbinafine is also a moderate-strong inhibitor of CYP2D6, which does not affect capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

Potential Interaction

Capmatinib

Theophylline

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Theophylline is mainly metabolised by CYP1A2 and concentrations may increase due to inhibition of CYP1A2 by capmatinib. After coadministration with caffeine, a CYP1A2 substrate, the AUC of caffeine increased by 134%. Coadministration should be avoided as theophylline toxicity may be increased. If coadministration is unavoidable, monitor closely for theophylline toxicity and decrease the dose of theophylline in accordance with the label.

Description:

See summary

No Interaction Expected

Capmatinib

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

Capmatinib

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, which are not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

Potential Interaction

Capmatinib

Ticagrelor

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Ticagrelor is a substrate of CYP3A4 and P-gp and concentrations may increase due to inhibition of P-gp by capmatinib. After coadministration with digoxin, a P-gp substrate, the AUC of digoxin increased by 47%. Coadministration should be avoided as ticagrelor toxicity may be increased. If coadministration is unavoidable, monitor closely for ticagrelor toxicity and decrease the dose in accordance with the label. Ticagrelor is also a weak inhibitor of CYP3A4. Concentrations of capmatinib may increase due to weak inhibition of CYP3A by ticagrelor, but this is unlikely to be clinically significant.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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. This is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

Tolbutamide

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tolbutamide is mainly metabolised by CYP2C9 and to a lesser extent by CYPs 2C8 and 2C19, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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. This is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib. Furthermore, OAT1/3 are the major transporters of loop and thiazide diuretics and are not affected by capmatinib. 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.

Description:

See summary

No Interaction Expected

Capmatinib

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. This is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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. This is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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. This is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

Potential Weak Interaction

Capmatinib

Trimethoprim/Sulfamethoxazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. 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). Trimethoprim concentrations may increase due to inhibition of CYP1A2 by capmatinib. After coadministration with caffeine, a CYP1A2 substrate, the AUC of caffeine increased by 134%. Coadministration should be monitored for trimethoprim toxicity. No a priori dose adjustment is required. Sulfamethoxazole is metabolised by CYP2C9, which is not affected by capmatinib. Trimethoprim is a weak CYP2C8 inhibitor and in vitro data also suggest that trimethoprim is an inhibitor of OCT2 and MATE1, which do not affect capmatinib. Sulfamethoxazole is a weak inhibitor of CYP2C9, which does not affect capmatinib either.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

Potential Weak Interaction

Capmatinib

Tropisetron

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Tropisetron is metabolised mainly by CYP2D6, which is not affected by capmatinib. Additionally, tropisetron is a substrate of P-gp and concentrations may increase due to inhibition of P-gp by capmatinib. After coadministration with digoxin, a P-gp substrate, the AUC of digoxin increased by 47%. Coadministration should be monitored for tropisetron toxicity. No a priori dose adjustment is required.

Description:

See summary

No Interaction Expected

Capmatinib

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 metabolized by CYP3A4 and to a lesser extent CYP1A2 and CYP2D6. Concentrations may increase due to inhibition of CYP1A2 by capmatinib. Howvever, as CYP1A2 represents a minor pathway this is unlikely to be clinically significant.

Description:

See summary

No Interaction Expected

Capmatinib

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 metabolised by glucuronidation (50%) and mitochondrial beta-oxidation (30-40%). To a lesser extent (10%) valproic acid is metabolised by CYP2C9 and CYP2C19, which is not affected by capmatinib. In addition, valproic acid is an inhibitor of CYP2C9, which does not affect capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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), which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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. This is not affected by capmatinib.

Description:

See summary

Potential Weak Interaction

Capmatinib

Verapamil

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Verapamil is metabolised mainly by CYP3A4 and to a lesser extent by CYPs 1A2, 2C8, and 2C9. Concentrations may increase due to inhibition of CYP1A2 by capmatinib. After coadministration with caffeine, a CYP1A2 substrate, the AUC of caffeine increased by 134%. Coadministration should be monitored for verapamil toxicity. No a priori dose adjustment of verapamil is required. Moreover, verapamil is an inhibitor of CYP3A4 (moderate) and P-gp (strong). Concentrations of capmatinib may increase due to moderate inhibition of CYP3A by verapamil. It is predicted that a moderate CYP3A inhibitor may increase capmatinib exposure by 30%. Coadministration should be monitored as toxicity of capmatinib may be increased. No a priori dose adjustment is required. If treatment-toxicities occur, a dose reduction to 300 mg twice daily should be considered.

Description:

See summary

Potential Weak Interaction

Capmatinib

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 and is a substrate of P-gp. Concentrations may increase due to inhibition of P-gp by capmatinib. After coadministration with digoxin, a P-gp substrate, the AUC of digoxin increased by 47%. Coadministration should be monitored for vildagliptin toxicity. No a priori dose adjustment is required.

Description:

See summary

No Interaction Expected

Capmatinib

Vitamin E

Quality of Evidence: Very Low

Summary:

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

Description:

See summary

Potential Interaction

Capmatinib

Voriconazole

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but should be approached with caution. Voriconazole is metabolised by CYP2C19 (major pathway) and to a lesser extent by CYP3A4 and CYP2C9. This is not affected by capmatinib. Voriconazole is also a strong inhibitor of CYP3A4 and a weak inhibitor of CYPs 2C9, 2C19, and 2B6. Concentrations of capmatinib may increase due to strong inhibition of CYP3A by voriconazole. After coadministration with itraconazole, a strong CYP3A4 inhibitor, exposure increased by 42% (no change Cmax). Monitor closely for capmatinib toxicities. If treatment-limiting toxicities occur, a dose reduction should be considered, e.g., from a daily dose of 800 mg (400 mg twice daily) to a daily dose of 500 mg (300 mg in the morning, 200 mg in the evening).

Description:

See summary

Potential Interaction

Capmatinib

Warfarin

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but is not recommended. Warfarin is a mixture of enantiomers which are metabolised by different cytochromes. R-warfarin is primarily metabolised by CYP1A2 and CYP3A4 and concentrations may increase due to inhibition of CYP1A2 by capmatinib. After coadministration with caffeine, a CYP1A2 substrate, the AUC of caffeine increased by 134%. Coadministration should be avoided as warfarin toxicity may be increased. If coadministration is unavoidable, monitor closely for warfarin toxicity and monitor INR/PT. S-warfarin (more potent) is metabolised by CYP2C9, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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 and are not affected by capmatinib. 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.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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). This is not affected by capmatinib.

Description:

See summary

No Interaction Expected

Capmatinib

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. This is not affected by capmatinib.

Description:

See summary

Potential Weak Interaction

Capmatinib

Zolpidem

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Zolpidem is metabolised mainly by CYP3A4 and to a lesser extent by CYP2C9, CYP2C19, CYP2D6, and CYP1A2. Concentrations may increase due to inhibition of CYP1A2 by capmatinib. After coadministration with caffeine, a CYP1A2 substrate, the AUC of caffeine increased by 134%. Coadministration should be monitored for zolpidem toxicity. No a priori dose adjustment is required.

Description:

See summary

No Interaction Expected

Capmatinib

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. This is not affected by capmatinib.

Description:

See summary

Potential Weak Interaction

Capmatinib

Zotepine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied but care should be taken. Zotepine is mainly metabolized by CYP3A4 and to a lesser extent by CYP1A2 and CYP2D6. Concentrations may increase due to inhibition of CYP1A2 by capmatinib. After coadministration with caffeine, a CYP1A2 substrate, the AUC of caffeine increased by 134%. Coadministration should be monitored for zotepine toxicity. No a priori dose adjustment is required.

Description:

See summary

No Interaction Expected

Capmatinib

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, which is not affected by capmatinib.

Description:

See summary