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. 

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Acenocoumarol is mainly metabolized by CYP2C9 and to a lesser extent by CYP1A2 and CYP2C19. Sunitinib does not inhibit or induce CYPs. However, an increased risk of bleeding is possible with sunitinib in combination with coumarins and close monitoring of INR/PT is recommended.

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 metabolized by glucuronidation (by several UGT, major UGT1A6). Sunitinib does not inhibit or induce CYPs or UGTs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as agomelatine is metabolised predominantly via CYP1A2. Sunitinib does not inhibit or induce CYPs.

Coadministration has not been studied. Alendronate is not metabolised and is cleared from the plasma by uptake into bone and elimination via renal excretion. Although no pharmacokinetic interaction is expected, alendronate should be separated from food or other medicinal products and patients must wait at least 30 minutes after taking alendronate before taking any other oral medicinal product. Osteonecrosis of the jaw has been reported in an increasing number of renal cell cancer patients since the use of combined therapies consisting of nitrogen-containing bisphosphonates and antiangiogenic targeted agents. This suggests that angiogenesis suppression might increase the risk of osteonecrosis of the jaw when coadministered with bisphosphonates. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Alfentanil undergoes extensive CYP3A4 metabolism but sunitinib is not an inducer or inhibitor of cytochrome P450 isozymes. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as alfuzosin is metabolized by CYP3A. Sunitinib does not inhibit or induce CYPs. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Aliskiren is minimally metabolized and is mainly excreted unchanged in faeces. However, P-glycoprotein is a major determinant of aliskiren bioavailability. Therefore, inhibition of P-gp by sunitinib may increase aliskiren concentrations. If the combination appears necessary, monitoring of blood pressure is recommended.

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely as allopurinol is converted to oxipurinol by xanthine oxidase and aldehyde oxidase. Sunitinib not interfere with this metabolic pathway. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. In vitro data indicate that alosetron is metabolized by CYP2C9, 3A4 and 1A2. Sunitinib does not inhibit of induce CYPs. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Alprazolam is mainly metabolized by CYP3A4. Sunitinib does not inhibit or induce CYPs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Sunitinib is freely soluble from pH 1.2 to 6.8 and decreased absorption of sunitinib would not be expected in combination with antacids.

Coadministration has not been studied. Ambrisentan is metabolised by glucuronidation via UGTs 1A3, 1A9 and 2B7, and to a lesser extent by CYP3A4 and CYP2C19. Ambrisentan is also a substrate of P-gp. Sunitinib is an inhibitor of P-gp and may increase concentrations of ambrisentan. The clinical relevance of this interaction is unknown.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as amikacin is eliminated by glomerular filtration.

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. Sunitinib is unlikely to affect amiloride renal elimination.

Coadministration has not been studied. Sunitinib should be used with caution when co-administered with a drug with a known risk of Torsade de Pointes. In patients, therapeutic doses of sunitinib have been shown to prolong the QTc interval with a median of 9.6 msec. If coadministration is necessary, close monitoring including ECG assessment is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amisulpride is weakly metabolized and is primarily eliminated renally (possibly via OCT). Sunitinib is unlikely to significantly affect amisulpride elimination. 

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Amitriptyline is metabolised predominantly by CYP2D6 and CYP2C19. Sunitinib does not interact with this metabolic pathway. However, caution is needed when sunitinib is coadministered with a drug with a known risk of Torsade de Pointes. In patients, therapeutic doses of sunitinib have been shown to prolong the QTc interval. If coadministration is necessary, close monitoring including ECG assessment is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amlodipine is metabolized by CYP3A4. Sunitinib does not inhibit or induce CYPs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as amoxicillin is mainly excreted in the urine by glomerular filtration and tubular secretion. In vitro data indicate that amoxicillin is a substrate of OAT3. Sunitinib is unlikely to interfere with amoxicillin renal elimination.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely as amphotericin is not appreciably metabolized and is eliminated to a large extent in the bile. Sunitinib does not interfere with amphotericin B elimination pathway. However, the European SPC for amphotericin states that concomitant use of amphotericin B and antineoplastic agents can increase the risk of renal toxicity, bronchospasm and hypotension. Furthermore, amphotericin B has a possible risk of QT interval prolongation. Therefore, caution is needed when sunitinib is co-administered with amphotericin B. In patients, therapeutic doses of sunitinib have been shown to prolong the QTc interval. If coadministration is necessary, close monitoring including ECG assessment is recommended.

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

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 temperature. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Sunitinib is freely soluble from pH 1.2 to 6.8 and decreased absorption of sunitinib would not be expected in combination with antacids.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Apixaban is metabolized by CYP3A4 and to a lesser extent by CYP1A2, CYP2C8, CYP2C9 and CYP2C19. Sunitinib does not inhibit or induce CYPs. 

Coadministration has not been studied but should be approached with caution. Aprepitant is mainly metabolised by CYP3A4 and to a lesser extent by CYP1A2 and CYP2C19. Sunitinib does not inhibit or induce CYPs. However, during treatment aprepitant is a moderate inhibitor of CYP3A4 and may increase sunitinib concentrations during the three days of coadministration. Therefore, coadministration is not recommended. If coadministration is unavoidable, reduce the sunitinib dose by approximately 50%. Monitor closely for sunitinib toxicity. After treatment aprepitant is a weak inducer of CYP3A4, CYP2C9 and UGT. Concentrations of sunitinib may decrease due to weak induction of CYP3A4, but this is not considered to be clinically relevant.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Asenapine is metabolized by glucuronidation (UGT1A4) and oxidative metabolism (CYP1A2 (major) and CYP3A4, 2D6 (minor). Sunitinib does not inhibit or induce CYPs.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely as astemizole is metabolized by CYPs 2D6, 2J2 and 3A4. 

However, caution is needed when sunitinib is co-administered with a drug with a known risk of Torsade de Pointes. In patients, therapeutic doses of sunitinib have been shown to prolong the QTc interval. If coadministration is necessary, close monitoring including ECG assessment is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as atenolol is mainly eliminated unchanged in the kidney, predominantly by glomerular filtration. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Atorvastatin is metabolized by CYP3A4 and is a substrate of P-gp. Sunitinib does not inhibit or induce CYPs. However, inhibition of P-gp by sunitinib may increase atorvastatin concentrations. It is recommended to start with the lowest dose and titrate up to the desired clinical effect while monitoring for safety.

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 metabolized analogously to natural purines. Sunitinib does not interfere with this metabolic pathway. However, due to the risk of additive haematological toxicity, haematological parameters should be monitored if coadministered.

Coadministration has not been studied. Azithromycin is mainly eliminated via biliary excretion and animal data suggest this may occur via P-glycoprotein and MRP2. Therefore, azithromycin concentrations may potentially increase due to inhibition of P-gp by sunitinib. No effect on sunitinib concentrations is expected. Caution should be taken when using azithromycin with drugs that are known to prolong the QT interval. In patients, therapeutic doses of sunitinib have been shown to prolong the QTc interval. If coadministration is necessary, close monitoring including ECG assessment is recommended.

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. Sunitinib does not interact with this pathway. 

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely as bedaquiline is metabolised by CYP3A4. Sunitinib does not inhibit or induce CYPs. However, bedaquiline prolongs the QTc interval and if coadministered with sunitinib an additive or synergistic effect on QT prolongation cannot be excluded. If coadministration is necessary, close monitoring including ECG assessment is recommended. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bendroflumethiazide is mainly eliminated by hepatic metabolism (70%) and excreted unchanged in the urine (30%) via OAT1 and OAT3. In vitro data indicate that bendroflumethiazide inhibits these renal transporters but a clinically relevant drug interaction is unlikely in the range of observed clinical concentrations. In addition, there is no evidence that bendroflumethiazide inhibits or induces CYP450 enzymes and therefore is unlikely to impact sunitinib.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Bepridil is metabolized by CYP2D6 (major) and 3A4. Sunitinib does not inhibit or induce CYPs. However, caution is needed when co-administering sunitinib with a drug with a known risk of Torsade de Pointes. In patients, therapeutic doses of sunitinib have been shown to prolong the QTc interval. If coadministration is necessary, close monitoring including ECG assessment is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Betamethasone is metabolized by CYP3A4. Sunitinib does not inhibit or induce CYPs. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as half of bezafibrate dose is eliminated unchanged in the urine. In vitro data suggest that bezafibrate inhibits the renal transporter OAT1. 

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. 

Coadministration has not been studied. Bisoprolol is partly metabolized by CYP3A4 and CYP2D6 and partly eliminated unchanged in the urine. Sunitinib does not inhibit or induce CYPs. However, bisoprolol is a substrate for P-gp and concentrations may potentially increase due to inhibition of P-gp by sunitinib. The clinical relevance of this interaction is unknown and monitoring of blood pressure may be required.

Coadministration has not been studied. Bosentan is a substrate and inducer of CYP3A4 and CYP2C9 and could potentially decrease sunitinib exposure. In a phase III study, imatinib concentrations, on average, decreased by 33% (95% CI 18%, 45%) in the presence of bosentan. Imatinib and sunitinib are both are metabolized mainly by CYP3A4 and a similar result may occur with sunitinib. If coadministration is necessary, close monitoring is required.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bromazepam undergoes oxidative biotransformation. Drug-drug interaction studies indicate that CYP3A4 plays a minor role in bromazepam metabolism, but other cytochromes such as CYP2D6 or CYP1A2 may play a role. Sunitinib does not inhibit or induce CYPs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Budesonide is metabolized by CYP3A4. Sunitinib does not inhibit or induce CYPs.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bupropion is primarily metabolized by CYP2B6. Sunitinib does not inhibit or induce CYPs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Buspirone is metabolized by CYP3A4. Sunitinib does not inhibit or induce CYPs.

Coadministration has not been studied but a clinically significant pharmacokinetic interaction is unlikely. Calcium is eliminated through faeces, urine and sweat. 

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. 

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. Sunitinib does not interfere with capreomycin renal elimination.

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. Sunitinib does not interfere with captopril elimination.

Coadministration has not been studied but should be avoided. Carbamazepine is primarily metabolised by CYP3A4 and to a lesser extent by CYP2C8. Sunitinib does not inhibit or induce CYPs. However, carbamazepine is an inducer of CYPs 2C8 (strong), 2C9 (strong), 3A4 (strong), 1A2 (weak), 2B6 and UGT1A1. Significant decreases in sunitinib plasma concentrations may occur due to induction of CYP3A4. If coadministration is clinically necessary, the product labels for sunitinib recommend a dose increase in 12.5 mg increments up to a maximum of 87.5 mg per day, based on careful monitoring of tolerability. Monitoring of sunitinib plasma concentrations should be considered, if available.

Coadministration has not been studied. Carvedilol undergoes glucuronidation via UGTs 1A1, 2B4 and 2B7, and metabolism via CYP2D6 and to a lesser extent CYPs 2C9 and 1A2. Sunitinib does not inhibit or induce CYPs. However, carvedilol is a substrate for P-gp and concentrations may potentially increase due to inhibition of P-gp by sunitinib. The clinical relevance of this interaction is unknown and monitoring of blood pressure may be required.

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. Sunitinib does not interact with this metabolic pathway. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cefalexin is predominantly eliminated unchanged renally by glomerular filtration and tubular secretion via OAT1 and MATE1. Sunitinib does not interfere with cefalexin renal elimination.

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. Sunitinib does not interfere with cefazolin renal elimination.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as cefixime is renally excreted predominantly by glomerular filtration. Sunitinib does not interfere with cefixime renal elimination.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as ceftazidime is excreted predominantly by renal glomerular filtration. Sunitinib does not interfere with ceftazidime renal elimination.

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. Sunitinib does not interfere with ceftriaxone renal elimination.

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

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 inhibits OCT2. Sunitinib is unlikely to interact with cetirizine’s renal elimination.

Coadministration has not been studied. In vitro studies have shown that chloramphenicol inhibits CYP3A4. Coadministration may potentially increase levels of sunitinib via this mechanism, increasing the risk of adverse events. The clinical significance of this interaction is unknown and close monitoring is recommended. Ocular use: Although chloramphenicol is systemically absorbed when used topically in the eye, the concentrations used are unlikely to cause a clinically significant interaction. 

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Chlorphenamine is predominantly metabolized in the liver via CYP2D6. Sunitinib is unlikely to interact with this pathway. 

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Chlorpromazine is metabolized mainly by CYP2D6, but also by CYP1A2. Sunitinib does not interact with this metabolic pathway. However, caution is needed when sunitinib is co-administered with a drug with a known risk of Torsade de Pointes. In patients, therapeutic doses of sunitinib have been shown to prolong the QTc interval. If coadministration is necessary, close monitoring including ECG assessment is recommended.

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. 

Coadministration has not been studied. Ciclosporin is a substrate of CYP3A4 and P-gp, and inhibits CYP3A4 and OATP1B1. Ciclosporin may potentially increase sunitinib concentrations due to CYP3A4 inhibition. No a priori dosage adjustment is commended for sunitinib, but close monitoring is recommended.

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. 

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely as cimetidine is unlikely to alter sunitinib absorption. Sunitinib is freely soluble from pH 1.2 to 6.8. Therefore, decreased absorption of sunitinib is not expected in combination with H2-antagonists and proton pump inhibitors. In vitro data indicate that cimetidine inhibits OAT1 and OCT2 but at concentrations much higher than the observed clinical concentrations. Sunitinib does not interact with this pathway. 

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Ciprofloxacin is primarily eliminated unchanged in the kidneys by glomerular filtration and tubular secretion via OAT3. Ciprofloxacin is also metabolised and partially cleared through the bile and intestine. Sunitinib does not interfere with the elimination of ciprofloxacin. Although ciprofloxacin is an inhibitor of CYP1A2 and CYP3A4, no clinically significant effect on sunitinib is expected. However, caution should be taken when using ciprofloxacin with drugs that are known to prolong the QT interval. In patients, therapeutic doses of sunitinib have been shown to prolong the QTc interval. If coadministration is necessary, monitoring including ECG assessment is recommended.

Coadministration has not been studied and should be avoided. Cisapride is metabolised by CYP3A4. Sunitinib does not inhibit or induce CYPs. However, sunitinib should be used with caution when co-administered with a drug with a known risk of Torsade de Pointes. 

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Citalopram is metabolized by CYP2C19 (38%), 2D6 (31%) and 3A4 (31%). Sunitinib does not inhibit or induce CYPs. However, caution is needed when sunitinib is co-administered with a drug with a known risk of Torsade de Pointes. In patients, therapeutic doses of sunitinib have been shown to prolong the QTc interval. If coadministration is necessary, close monitoring including ECG assessment is recommended.

Coadministration has not been studied and is not recommended. Clarithromycin may increase sunitinib concentrations due to inhibition of CYP3A4 and P-gp. Concurrent use of potent CYP3A4 inhibitors should be avoided because sunitinib is relatively toxic and can cause dose-related QT-prolongation. If coadministration is unavoidable, monitor closely for sunitinib toxicity and reduce sunitinib dose in steps of 12.5 mg (25-33% dose reduction). For example, the dose of sunitinib may need to be reduced from 50 mg to 37.5 mg daily for GIST and MRCC in a 4/2 week intermittent scheme (25% dose reduction) and from 37.5 mg to 25 mg in a continuously daily dosing scheme for pNET, MRCC and GIST (33% dose reduction), based on careful monitoring of tolerability. Consider monitoring of sunitinib plasma concentrations, if available. ECG assessment is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clavulanic acid is extensively metabolized (likely non CYP mediated pathway) and excreted in the urine by glomerular filtration. Sunitinib does not inhibit or induce CYPs. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clemastine is predominantly metabolized in the liver via CYP2D6. Sunitinib is unlikely to interact with this pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clindamycin is metabolized by CYP3A4. Sunitinib does not inhibit or induce CYPs. 

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

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Clofazimine is largely excreted unchanged in the faeces, both as unabsorbed drug and via biliary excretion. However, in patients therapeutic doses of sunitinib have been shown to prolong the QTc interval. Caution should be taken when using clofazimine with drugs that are known to prolong the QT interval. If coadministration is necessary, close monitoring including ECG assessment is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clofibrate is hydrolyzed to an active metabolite, clofibric acid. Excretion of clofibric acid glucuronide is possibly performed via OAT1. Sunitinib does not interfere with clofibrate elimination.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Clomipramine is metabolized by CYP3A4, 1A2 and 2C19 to desmethylclomipramine, an active metabolite which has a higher activity than the parent drug. In addition, clomipramine and desmethylclomipramine are metabolized by CYP2D6. Sunitinib does not inhibit or induce CYPs. However, caution is needed when sunitinib is co-administered with a drug with a known risk of Torsade de Pointes. In patients, therapeutic doses of sunitinib have been shown to prolong the QTc interval. If coadministration is necessary, close monitoring including ECG assessment is recommended.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clopidogrel is a prodrug and is converted to its active metabolite via CYPs 3A4, 2B6, 2C19 and 1A2. Sunitinib does not inhibit or induce CYPs. 

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 metabolized to oxazepam by CYP3A4. Sunitinib does not inhibit or induce CYPs.

Coadministration has not been studied but based on the 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. Sunitinib does not interact with this metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Clozapine is metabolised mainly by CYP1A2 and CYP3A4, and to a lesser extent by CYP2C19 and CYP2D6. Sunitinib does not inhibit or induce CYPs. However, caution is needed when sunitinib is coadministered with a drug with a known risk of Torsade de Pointes. In patients, therapeutic doses of sunitinib have been shown to prolong the QTc interval. If coadministration is necessary, close monitoring including ECG assessment is recommended. Furthermore, due to the risk of additive haematological toxicity, haematological parameters should be monitored if coadministered.

Coadministration has not been studied. Codeine is converted via CYP2D6 to morphine, an active metabolite with analgesic and opioid properties. Morphine is further metabolised by conjugation with glucuronic acid to morphine-3-glucuronide (inactive) and morphine-6-glucuronide (active). Morphine is also a substrate of P-gp. Sunitinib is an inhibitor of P-gp and may increase concentrations of morphine. The clinical relevance of this interaction is unknown. Furthermore, codeine is converted via CYP3A4 to norcodeine, an inactive metabolite. Sunitinib does not inhibit or induce CYPs or UGTs.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely as colchicine is metabolized by CYP3A4. Sunitinib does not inhibit or induce CYPs. In a case report is was shown that a patient experienced colchicine toxicity probably due to P-gp inhibition of by sunitinib. However this patient also exhibited other risk factors for colchicine toxicity, namely renal impairment and coadministration with diltiazem. Use colchicine with caution.

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Cycloserine is predominantly excreted renally via glomerular filtration. Sunitinib does not interact with this metabolic pathway.

Coadministration has not been studied. Dabigatran is a substrate of P-gp and is renally excreted. Sunitinib is an inhibitor of P-gp and may increase concentrations of dabigatran. As the clinical relevance of this interaction is unknown, monitoring may be required.

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. Sunitinib does not interfere with the renal excretion of dalteparin. 

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 CYP P450 enzymes. Sunitinib does not inhibit or induce CYPs. 

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely as desipramine is metabolized by CYP2D6. Sunitinib does not inhibit or induce CYPs. However, caution is needed when sunitinib is co-administered with a drug with a known risk of Torsade de Pointes. In patients, therapeutic doses of sunitinib have been shown to prolong the QTc interval. If coadministration is necessary, close monitoring including ECG assessment is recommended.

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. Sunitinib does not inhibit or induce CYPs.

Coadministration has not been studied. Dexamethasone has been described as a weak inducer of CYP3A4 and could possibly decrease sunitinib plasma concentrations. However, the clinical relevance of CYP3A4 induction by dexamethasone has not been established yet. Monitoring may be required. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dextropropoxyphene is mainly metabolized by CYP3A4. Sunitinib does not inhibit or induce CYPs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Diamorphine is rapidly metabolized 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). Sunitinib does not interact with this metabolic pathway. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Diazepam is metabolized to nordiazepam (by CYP3A4 and 2C19) and to temazepam (mainly by CYP3A4. Sunitinib does not inhibit or induce CYPs.

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 oxidized by CYP2C9. Sunitinib does not inhibit or induce CYPs or UGTs.

Coadministration has not been studied. Digoxin is eliminated renally via the renal transporters OATP4C1 and P-glycoprotein. Sunitinib is an inhibitor of P-gp and may possibly increase digoxin concentrations. It is recommended that the lowest possible dose of digoxin should initially be given to patients on sunitinib. The digoxin dose should be carefully titrated to obtain the desired clinical effect while assessing the overall clinical state of the subject.

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. Sunitinib does not inhibit or induce CYPs or UGTs. 

Coadministration has not been studied. Diltiazem is metabolized by CYP3A4 and CYP2D6and sunitinib does not inhibit or induce CYPs. However, diltiazem is a moderate inhibitor of CYP3A4 and therefore could potentially increase sunitinib exposure. The clinical relevance of this interaction is unknown. No a priori dosage adjustment is recommended for sunitinib. Close monitoring of sunitinib tolerability is recommended. 

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Diphenhydramine is mainly metabolized by CYP2D6. Sunitinib does not interact with this metabolic pathway. However, caution is needed when sunitinib is co-administered with a drug with a known risk of Torsade de Pointes. In patients, therapeutic doses of sunitinib have been shown to prolong the QTc interval. If coadministration is necessary, close monitoring including ECG assessment is recommended. 

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. Sunitinib is unlikely to interfere with this pathway.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Disopyramide is metabolized by CYP3A4 (25%) and 50% of the drug is eliminated unchanged in the urine. Sunitinib does not interact with this metabolic pathway. However, caution is needed when co-administering sunitinib with a drug with a known risk of Torsade de Pointes. In patients, therapeutic doses of sunitinib have been shown to prolong the QTc interval. If coadministration is necessary, close monitoring including ECG assessment is recommended.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Dolasetron is converted by carbonyl reductase to its active metabolite, hydrodolasetron, which is mainly glucuronidated (60%) and metabolized by CYP2D6 (10-20%) and CYP3A4 (<1%). Sunitinib does not interfere with this pathway. However, dolasetron may prolong the QT interval and in sunitinib has been shown to prolong the QT interval. Caution should be taken when using dolasetron with drugs that are known to prolong the QT interval. If coadministration is necessary, close monitoring including ECG assessment is recommended.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Domperidone is mainly metabolized by CYP3A4. Sunitinib does not inhibit of induce CYPs. However, sunitinib should be used with caution when co-administered with a drug with a known risk of Torsade de Pointes. Sunitinib has been shown to prolong the QTc interval. If coadministration is necessary, close monitoring including ECG assessment is recommended.

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 sunitinib, or to be affected if co-administered with sunitinib.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Doxazosin is metabolized mainly by CYP3A4. Sunitinib does not inhibit or induce CYPs. 

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

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Doxycycline is excreted in the urine and faeces as unchanged active substance. Between 40%-60% of an administered dose can be accounted for in the urine. Sunitinib does not inhibit or induce CYPs. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dronabinol is mainly metabolized by CYP2C9 and to a lesser extent by CYP3A4. Sunitinib does not inhibit or induce CYPs. 

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. Sunitinib does not inhibit or induce CYPs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as dulaglutide is degraded by endogenous endopeptidases. Dulaglutide delays gastric emptying and could possibly decrease the absorption rate of concomitantly administered oral drugs. Since sunitinib is absorbed in 6-12h, the clinical relevance of delayed absorption is considered to be limited.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dutasteride is mainly metabolized by CYP3A4. Sunitinib does not inhibit or induce CYPs. 

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). Sunitinib does not inhibit or induce CYPs.

Coadministration has not been studied. Edoxaban plasma concentrations may increase due to inhibition of P-gp by sunitinib. The clinical relevance of this interaction is not known and monitoring may be required.

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Eltrombopag is metabolised by cleavage conjugation (via UGT1A1, UGT1A3) and oxidation (via CYP1A2 and CYP2C8). Sunitinib does not interact with this metabolic pathway.

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). 

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as eprosartan is largely excreted in bile and urine as unchanged drug. 

Coadministration has not been studied but based on the 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 component. Sunitinib does not interact with this metabolic pathway.

Coadministration has not been studied and is not recommended. Erythromycin may increase sunitinib concentrations due to inhibition of CYP3A4. Concurrent use of potent CYP3A4 inhibitors should be avoided because sunitinib is relatively toxic and can cause dose-related QT-prolongation. If coadministration is unavoidable, monitor closely for sunitinib toxicity and reduce sunitinib dose in steps of 12.5 mg (25-33% dose reduction). For example, the dose of sunitinib may need to be reduced from 50 mg to 37.5 mg daily for GIST and MRCC in a 4/2 week intermittent scheme (25% dose reduction) and from 37.5 mg to 25 mg in a continuously daily dosing scheme for pNET, MRCC and GIST (33% dose reduction), based on careful monitoring of tolerability. Consider monitoring of sunitinib plasma concentrations, if available. ECG assessment is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Escitalopram is metabolized by CYP2C19 (37%), 2D6 (28%) and 3A4 (35%) to form N-desmethylescitalopram. Sunitinib does not inhibit or induce CYPs. However, caution is needed when sunitinib is co-administered with a drug with a known risk of Torsade de Pointes. In patients, therapeutic doses of sunitinib have been shown to prolong the QTc interval. If coadministration is necessary, close monitoring including ECG assessment is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as esomeprazole is unlikely to alter sunitinib absorption. Sunitinib is freely soluble from pH 1.2 to 6.8. Therefore, decreased absorption of sunitinib is not expected in combination with H2-antagonists and proton pump inhibitors. Moreover, esomeprazole is metabolised by CYP2C19 and CYP3A4. Esomeprazole inhibits CYP2C19. Sunitinib does not interact with this pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Estazolam is metabolized to its major metabolite 4-hydroxyestazolam via CYP3A4. Sunitinib does not inhibit or induce CYPs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Estradiol is metabolized by CYP3A4, CYP1A2 and is glucuronidated. Sunitinib does not inhibit or induce CYPs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ethambutol is partly metabolized by alcohol dehydrogenase (20%) and partly eliminated unchanged in the faeces (20%) and in the urine (50%). Sunitinib does not interact with this metabolic pathway.

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

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Etonogestrel is metabolized by CYP3A4. Sunitinib does not inhibit or induce CYPs.

Everolimus is mainly metabolised by CYP3A4 and is a substrate of P-gp. Sunitinib is an inhibitor of P-gp and may increase concentrations of everolimus. In patients with metastatic renal cell carcinoma (n=20), coadministration of sunitinib (37.5 or 50 mg once daily, 4 weeks on/2 weeks off) and everolimus (2.5-5 mg daily or 20-30 mg once weekly, maximum tolerated dose) showed no pharmacokinetic interaction but increased toxicity was observed when everolimus was administered at 5 mg once daily. A schedule of 20 mg everolimus weekly/37.5 mg sunitinib was tolerated as chronic therapy. Since everolimus as an immunosuppressant is dosed much lower than as an anticancer therapy, no tolerability issues at reduced dose are expected. Close monitoring for everolimus toxicity is recommended. Due to the risk of additive haematological toxicity, haematological parameters should be monitored if coadministered.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as exenatide is cleared mainly by glomerular filtration. Exenatide delays gastric emptying and could possibly decrease the absorption rate of concomitantly administered oral drugs. Since sunitinib is absorbed in 6-12h, the clinical relevance of delayed absorption is considered to be limited.

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. Sunitinib does not interact with this metabolic pathway. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as famotidine is unlikely to alter sunitinib absorption. Sunitinib is freely soluble from pH 1.2 to 6.8. Therefore, decreased absorption of sunitinib is not expected in combination with H2-antagonists and proton pump inhibitors.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Felodipine is metabolized by CYP3A4. Sunitinib does not inhibit or induce CYPs.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fentanyl undergoes extensive CYP3A4 metabolism. Sunitinib does not inhibit or induce CYPs. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fexofenadine undergoes negligible metabolism and is mainly eliminated unchanged in the faeces. 

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

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

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Flecainide is metabolized mainly via CYP2D6, with a proportion (approximately 30%) of the parent drug also eliminated unchanged renally. Sunitinib does not interact with this metabolic pathway. However, caution is needed when co-administered sunitinib with a drug with a known risk of Torsade de Pointes. In patients, therapeutic doses of sunitinib have been shown to prolong the QTc interval. If coadministration is necessary, close monitoring including ECG assessment is recommended.

Coadministration has not been studied. Flucloxacillin is mainly eliminated renally partly by glomerular filtration and partly by active secretion via OAT1. Sunitinib does not interact with this metabolic pathway. However, flucloxacillin was shown to induce CYP3A4 and P-gp and could potentially decrease sunitinib exposure. Close monitoring is recommended.

Coadministration has not been studied and is not recommended as sunitinib concentrations may increase due to inhibition of CYP3A4 by fluconazole. Coadministration of sunitinib and ketoconazole increased total sunitinib plus active metabolite Cmax and AUC by 49% and 51%, respectively. The effect of fluconazole is expected to be comparable. Concurrent use of CYP3A4 inhibitors should be avoided, because sunitinib is relatively toxic and can cause dose-related QT-prolongation. If coadministration is unavoidable, monitor closely for sunitinib toxicity and reduce sunitinib dose in steps of 12.5 mg (25-33% dose reduction). For example, the dose of sunitinib may need to be reduced from 50 mg to 37.5 mg daily for GIST and MRCC in a 4/2 week intermittent scheme (25% dose reduction) and from 37.5 mg to 25 mg in a continuously daily dosing scheme for pNET, MRCC and GIST (33% dose reduction), based on careful monitoring of tolerability. Consider monitoring of sunitinib plasma concentrations, if available. ECG assessment is recommended.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fludrocortisone is metabolized in the liver to inactive metabolites, possibly via CYP3A. Sunitinib does not inhibit or induce CYPs. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Flunitrazepam is metabolized mainly via CYP3A4 and 2C19. Sunitinib does not inhibit or induce CYPs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fluoxetine is metabolized by CYP2D6 and 2C9 and to a lesser extent by 2C19 and 3A4 to form norfluoxetine. Sunitinib does not inhibit or induce CYPs. 

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Fluphenazine is metabolised by CYP2D6. Sunitinib does not inhibit or induce CYPs. However, caution is needed when sunitinib is co-administered with a drug with a known risk of Torsade de Pointes. In patients, therapeutic doses of sunitinib have been shown to prolong the QTc interval. If coadministration is necessary, close monitoring including ECG assessment is recommended.

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. Sunitinib does not inhibit or induce CYPs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fluticasone is metabolized by CYP3A4. Sunitinib does not inhibit or induce CYPs. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as fluvastatin is mainly metabolized by CYP2C9. Sunitinib does not inhibit or induce CYPs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fluvoxamine is metabolized mainly by CYP2D6 and to a lesser extent by CYP1A2. Sunitinib does not inhibit or induce CYPs. However, fluvoxamine inhibits CYPs 1A2, 2C19, 3A4, 2C9 and sunitinib concentrations may be slightly increased if co-administered with fluvoxamine. The clinical relevance of this interaction is unknown and monitoring may be required.

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. Sunitinib does not interact with this metabolic pathway.

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 being another pathway. As multiple CYP450 and UGT enzymes catalyze the transformation the potential for a pharmacokinetic interaction is low and sunitinib does not interact with these metabolic pathways

Coadministration has not been studied but should be approached with caution. Fosaprepitant is rapidly, almost completely, converted to the active metabolite aprepitant. Sunitinib does not interact with this metabolic pathway. Aprepitant is mainly metabolised by CYP3A4 and to a lesser extent by CYP1A2 and CYP2C19. Sunitinib does not inhibit or induce CYPs. However, during treatment aprepitant is a moderate inhibitor of CYP3A4 and may increase sunitinib concentrations during the three days of coadministration. Therefore, coadministration is not recommended. If coadministration is unavoidable, reduce the sunitinib dose by approximately 50%. Monitor closely for sunitinib toxicity. After treatment aprepitant is a weak inducer of CYP3A4, CYP2C9 and UGT. Concentrations of sunitinib may decrease due to weak induction of CYP3A4, but this is not considered to be clinically relevant.

Coadministration has not been studied but should be avoided. Fosphenytoin is rapidly converted to the active metabolite phenytoin. Phenytoin is mainly metabolised by CYP2C9 and to a lesser extent by CYP2C19. Sunitinib does not interact with this pathway. However, phenytoin is a potent inducer of CYP3A4, UGT and P-gp. Concentrations of sunitinib may decrease due to induction of CYP3A4. Therefore, coadministration should be avoided. If coadministration is unavoidable, the dose of sunitinib may need to be increased in increments of 12.5 mg up to a maximum of 87.5 mg daily, with careful monitoring of tolerability. Consider monitoring of sunitinib plasma concentrations, if available.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Furosemide is glucuronidated mainly in the kidney (UGT1A9) and to a lesser extent in the liver (UGT1A1). A large proportion of furosemide is also eliminated unchanged renally (via OATs). In vitro data indicate that furosemide is an inhibitor of the renal transporters OAT1/OAT3. Sunitinib does not interfere with furosemide elimination.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as gabapentin is cleared mainly by glomerular filtration. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Gemfibrozil is metabolised by UGT2B7. Sunitinib does not interact with this metabolic pathway. 

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. Sunitinib does not interact with this metabolic pathway. 

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. Sunitinib does not inhibit or induce CYPs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Glibenclamide is mainly metabolized by CYP3A4 and to a lesser extent by CYP2C9. Sunitinib does not inhibit or induce CYPs.

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

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

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

Coadministration has not been studied. Granisetron is metabolized by CYP3A4. Sunitinib does not inhibit of induce CYPs. However, granisetron is substrate of P-gp and concentrations may potentially increase due to inhibition of P-gp by sunitinib. Moreover, granisetron may prolong the QT interval and sunitinib has been shown to prolong the QTc interval. Caution should be taken when using granisetron with drugs that are known to prolong the QT interval. If coadministration is necessary, clinical monitoring including ECG assessment is recommended.

Grapefruit juice is known to inhibit CYP3A4 enzymes and could potentially increase sunitinib concentrations. Coadministration of sunitinib and grapefruit juice in 8 patients increased sunitinib AUC by 11%. The increased exposure in the study was not considered clinically relevant. However, the magnitude of this potential interaction is difficult to predict as the effect of grapefruit juice is concentration-, dose- and preparation-dependent and varies widely across brands. The product labels for sunitinib advise to avoid coadministration with grapefruit juice.

Coadministration of green tea was associated with decreased therapeutic effects in a case report. In an additional rat model study an interaction of the green tea polyphenol epigallocatechin gallate (EGCG) with sunitinib was shown. The bioavailability of sunitinib reduced markedly by coadministration of EGCG via complex formation in the gastro-intestinal tract (AUC ratio 0.5). The use of green tea should be avoided during sunitinib treatment.

Coadministration has not been studied. Less than 1% of a griseofulvin dose is excreted unchanged via the kidneys. Sunitinib does not interfere with griseofulvin elimination pathway. However, griseofulvin is a liver microsomal enzyme inducer and may lower plasma levels, and therefore reduce the efficacy, of concomitantly administered medicinal products metabolized by CYP3A4, such as sunitinib. 

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Haloperidol has a complex metabolism as it undergoes glucuronidation (UGT2B7>1A4, 1A9), carbonyl reduction as well as oxidative metabolism (CYP3A4, 2D6). Sunitinib does not inhibit or induce CYPs. However, caution is needed when sunitinib is co-administered with a drug with a known risk of Torsade de Pointes. In patients, therapeutic doses of sunitinib have been shown to prolong the QTc interval. If coadministration is necessary, close monitoring including ECG assessment is recommended.

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. Sunitinib does not interact with this metabolic pathway.

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. Although in vitro studies have suggested that hydralazine is a mixed enzyme inhibitor, which may weakly inhibit CYP3A4 and CYP2D6, it is not expected that this will lead to a clinical relevant interaction with sunitinib. 

Coadministration has not been studied. Hydrochlorothiazide is not metabolized and is cleared by the kidneys via OAT1. In vitro data indicate that hydrochlorothiazide is unlikely to inhibit OAT1 in the range of clinically relevant concentrations. Significant interactions are not expected with sunitinib.

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. Sunitinib does not inhibit or induce CYPs. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Hydrocortisone is metabolized by CYP3A4. Sunitinib does not inhibit or induce CYPs. 

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

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. Sunitinib not interact with this metabolic pathway. 

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Hydroxyurea is not a substrate of CYP enzymes or P-gp. However, coadministration may increase risk of gastro-intestinal toxicity, haematological toxicity or mucositis. Monitor haematological parameters if used concurrently.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Hydroxyzine is partly metabolized by alcohol dehydrogenase and partly by CYP3A4. Sunitinib does not inhibit or induce CYPs. However, caution is needed when sunitinib is co-administered with a drug with a known risk of Torsade de Pointes. In patients, therapeutic doses of sunitinib have been shown to prolong the QTc interval. If coadministration is necessary, close monitoring including ECG assessment is recommended.

Coadministration has not been studied. 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. Osteonecrosis of the jaw has been reported in an increasing number of renal cell cancer patients since the use of combined therapies consisting of nitrogen-containing bisphosphonates and antiangiogenic targeted agents. This suggests that angiogenesis suppression might increase the risk of osteonecrosis of the jaw when coadministered with bisphosphonates. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ibuprofen is metabolized mainly by CYP2C9 and to a lesser extent by CYP2C8 and direct glucuronidation. Sunitinib does not inhibit or induce CYPs or UGTs. 

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Iloperidone is metabolized by CYP3A4 and CYP2D6. Sunitinib does not inhibit or induce CYPs. However, caution is needed when sunitinib is co-administered with a drug with a known risk of Torsade de Pointes. In patients, therapeutic doses of sunitinib have been shown to prolong the QTc interval. If coadministration is necessary, close monitoring including ECG assessment is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Imipenem and cilastatin are eliminated by glomerular filtration and to a lesser extent, active tubular secretion. Sunitinib does not interact with this metabolic pathway. 

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Imipramine is metabolized by CYPs 3A4, 2C19 and 1A2 to desipramine. Imipramine and desipramine are both metabolized by CYP2D6. Sunitinib does not inhibit or induce CYPs. However, caution is needed when sunitinib is co-administered with a drug with a known risk of Torsade de Pointes. In patients, therapeutic doses of sunitinib have been shown to prolong the QTc interval. If coadministration is necessary, close monitoring including ECG assessment is recommended.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Indapamide is extensively metabolized by CYP P450. Sunitinib does not inhibit or induce CYPs. However, sunitinib has been shown to prolong the QTc interval and the use of indapamide in patients treated with QT prolonging medicinal products should be avoided. If coadministration is necessary, close monitoring including ECG assessment is recommended.

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

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. However, coadministration may increase risk of neutropenia, fatigue, and thrombocytopenia. Monitor haematological parameters if used concurrently.

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. 

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. Sunitinib does not interact with this metabolic pathway.

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

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

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. Sunitinib does not interact with this metabolic pathway. 

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. Sunitinib does not inhibit or induce CYPs. As renal elimination of unchanged drug is a minor pathway, there is little potential for an interaction.

Coadministration has not been studied and is not recommended as sunitinib concentrations may increase due to inhibition of CYP3A4 by itraconazole. Coadministration of sunitinib and ketoconazole increased total sunitinib plus active metabolite Cmax and AUC by 49% and 51%, respectively. The effect of itraconazole is expected to be comparable. Concurrent use of CYP3A4 inhibitors should be avoided, because sunitinib is relatively toxic and can cause dose-related QT-prolongation. If coadministration is unavoidable, monitor closely for sunitinib toxicity and reduce sunitinib dose in steps of 12.5 mg (25-33% dose reduction). For example, the dose of sunitinib may need to be reduced from 50 mg to 37.5 mg daily for GIST and MRCC in a 4/2 week intermittent scheme (25% dose reduction) and from 37.5 mg to 25 mg in a continuously daily dosing scheme for pNET, MRCC and GIST (33% dose reduction), based on careful monitoring of tolerability. Consider monitoring of sunitinib plasma concentrations, if available. ECG assessment is recommended.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Ivabradine is metabolized by CYP3A4. Sunitinib does not inhibit or induce CYPs. However, sunitinib has been shown to prolong the QTc interval and the product labels advise that the use of ivabradine in patients treated with QT prolonging medicinal products should be avoided. If the combination appears necessary, close ECG monitoring is needed.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as kanamycin is eliminated unchanged predominantly via glomerular filtration.

Coadministration of sunitinib and ketoconazole to healthy subjects increased total sunitinib plus active metabolite Cmax and AUC by 49% and 51%, respectively, due to inhibition of CYP3A4. Concurrent use of CYP3A4 inhibitors should be avoided, because sunitinib is relatively toxic and can cause dose-related QT-prolongation. If coadministration is unavoidable, monitor closely for sunitinib toxicity and reduce sunitinib dose in steps of 12.5 mg (25-33% dose reduction). For example, the dose of sunitinib may need to be reduced from 50 mg to 37.5 mg daily for GIST and MRCC in a 4/2 week intermittent scheme (25% dose reduction) and from 37.5 mg to 25 mg in a continuously daily dosing scheme for pNET, MRCC and GIST (33% dose reduction), based on careful monitoring of tolerability. Consider monitoring of sunitinib plasma concentrations, if available. ECG assessment is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Labetalol is mainly glucuronidated (via UGT1A1 and 2B7). Sunitinib does not interact with this metabolic pathway. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lacidipine is metabolized by CYP3A4. Sunitinib does not inhibit or induce CYPs. 

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. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as lansoprazole is unlikely to alter sunitinib absorption. Sunitinib is freely soluble from pH 1.2 to 6.8. Therefore, decreased absorption of sunitinib is not expected in combination with H2-antagonists and proton pump inhibitors. Moreover, lansoprazole is mainly metabolised by CYP2C19 and in lesser extent by CYP3A4. Sunitinib does not interact with this pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lercanidipine is mainly metabolized by CYP3A4. Sunitinib does not inhibit or induce CYPs. 

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

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Levofloxacin is eliminated renally mainly by glomerular filtration and active secretion (possibly OCT2). Sunitinib does not interact with this metabolic pathway. However, sunitinib should be used with caution when co-administered with a drug with a known risk of QTc interval prolongation. In patients therapeutic doses of sunitinib have been shown to prolong the QTc interval. If coadministration is necessary, close monitoring including ECG assessment is recommended.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Levomepromazine is metabolized by CYP2D6. Sunitinib does not inhibit or induce CYPs. However, caution is needed when sunitinib is co-administered with a drug with a known risk of Torsade de Pointes. In patients, therapeutic doses of sunitinib have been shown to prolong the QTc interval. If coadministration is necessary, close monitoring including ECG assessment is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Levonorgestrel is metabolized by CYP3A4 and is glucuronidated to a minor extent. Sunitinib does not interact with this metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Levonorgestrel is metabolized by CYP3A4 and is glucuronidated to a minor extent. Sunitinib does not interact with this metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Levothyroxine is metabolized by deiodination (by enzymes of deiodinase family) and glucuronidation. Sunitinib does not interact with levothyroxine metabolism. However, a case report showed that the plasma exposure to levothyroxine may be decreased when sunitinib is co-administered. Monitoring of TSH levels is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. CYP1A2 is the predominant enzyme involved in lidocaine metabolism in the range of therapeutic concentrations with a minor contribution from CYP3A4. Sunitinib does not inhibit or induce CYPs. 

Coadministration has not been studied and is not recommended. Linagliptin is mainly eliminated as parent compound in faeces with metabolism by CYP3A4 representing a minor elimination pathway. Linagliptin is a substrate for P-glycoprotein (P-gp) and is an inhibitor of CYP3A4. Linagliptin concentrations may increase due to inhibition of P-gp by sunitinib and sunitinib concentrations may increase due to inhibition of CYP3A4 by linagliptin. The clinical relevance of this interaction is unknown and close monitoring may be required.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Linezolid undergoes non CYP mediated metabolism. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as liraglutide is degraded by endogenous endopeptidases. 

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. 

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic 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. However, caution is needed when sunitinib is co-administered with a drug with a known risk of Torsade de Pointes. In patients, therapeutic doses of sunitinib have been shown to prolong the QTc interval. If coadministration is necessary, close monitoring including ECG assessment is recommended.

Coadministration of live vaccines (such as BCG vaccine; measles, mumps and rubella vaccines; varicella vaccines; typhoid vaccines; rotavirus vaccines; yellow fever vaccines; oral polio vaccine) has not been studied. In patients, who are receiving cytotoxics or other immunosuppressant drugs, use of live vaccines for immunisation is contraindicated. If coadministration is judged clinically necessary, use with extreme caution since generalized infections can occur.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Loperamide is mainly metabolized by CYP3A4 and CYP2C8. Sunitinib does not inhibit or induce CYPs. Although, loperamide is a substrate of P-gp and concentrations may increase due to inhibition of P-gp by sunitinib, this is unlikely to be clinically relevant.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lorazepam is eliminated by non-CYP-mediated pathways and no effect on plasma concentrations is expected when coadministered with sunitinib. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lormetazepam is mainly glucuronidated. Sunitinib does not interact with this metabolic pathway. 

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. Sunitinib does not interact with this metabolic pathway. 

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Macitentan is metabolized mainly by CYP3A4 and to a lesser extent by CYPs 2C19, 2C9 and 2C8. Sunitinib does not inhibit or induce CYPs. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Magnesium is eliminated in kidney, mainly by glomerular filtration. 

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Medroxyprogesterone is metabolized by CYP3A4. Sunitinib does not inhibit or induce CYPs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Medroxyprogesterone is metabolized by CYP3A4. Sunitinib does not inhibit or induce CYPs.

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

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. 

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

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

Coadministration has not been studied, but should be approached with caution. Metamizole may decrease sunitinib concentrations due to induction of CYP3A4. Decreases in sunitinib exposure can lead to decreased efficacy. Selection of an alternative concomitant medication with no or minimal enzyme or transporter induction potential is recommended. The clinical relevance of this interaction is unknown; monitoring and dose adjustment may be required.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metformin is mainly eliminated unchanged in the urine (via OCT2). Sunitinib does not interact with metformin metabolic and elimination pathway.

Coadministration has not been studied. Sunitinib should be used with caution when coadministered with a drug with a known risk of Torsade de Pointes. In patients, therapeutic doses of sunitinib have been shown to prolong the QTc interval. If coadministration is necessary, close monitoring including ECG assessment is recommended.

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. It is unlikely to affect the disposition of sunitinib, or to be altered by coadministration with sunitinib.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Methylphenidate is not metabolized by cytochrome P450 to a clinically relevant extent and does not inhibit cytochrome P450s. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Methylprednisolone is metabolized by CYP3A4. Sunitinib does not inhibit or induce CYPs. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metoclopramide is partially metabolized by CYP450 system (mainly CYP2D6). Sunitinib does not interact with this metabolic pathway. 

Coadministration has not been studied, but based on metabolism and clearance a clinically significant interaction is unlikely as metolazone is largely excreted unchanged in the urine. 

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

Coadministration has not been studied but 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). Since the mechanism of the interaction with CYP3A has not yet been identified, an interaction with sunitinib cannot be excluded and close monitoring is recommended.

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

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

Coadministration has not been studied. Miconazole inhibits CYP2C9 and CYP3A4 and could potentially increase sunitinib concentrations. Oromucosal coadministration may increase sunitinib concentrations due to inhibition of CYP3A4. Concurrent use of CYP3A4 inhibitors should be avoided, because sunitinib is relatively toxic and can cause dose-related QT-prolongation. If coadministration is unavoidable, monitor closely for sunitinib toxicity and reduce sunitinib dose in steps of 12.5 mg (25-33% dose reduction). For example, the dose of sunitinib may need to be reduced from 50 mg to 37.5 mg daily for GIST and MRCC in a 4/2 week intermittent scheme (25% dose reduction) and from 37.5 mg to 25 mg in a continuously daily dosing scheme for pNET, MRCC and GIST (33% dose reduction), based on careful monitoring of tolerability. Consider monitoring of sunitinib plasma concentrations, if available. ECG assessment is recommended. Note, no a priori dosage adjustment is recommended for sunitinib with dermal administration of miconazole, since systemic exposure of miconazole is limited when used topically.

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

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

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%). Sunitinib is unlikely to interfere with this pathways.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Mometasone is metabolized by CYP3A4. Sunitinib does not inhibit or induce CYPs. 

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Morphine is mainly glucuronidated to morphine-3-glucuronide (UGT2B7>UGT1A1) and, to a lesser extent, to the pharmacologically active morphine-6-glucuronide (UGT2B7>UGT1A1). Sunitinib does not interact with this metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Moxifloxacin is predominantly glucuronidated by UGT1A1. Sunitinib is unlikely to interfere with this pathway. However, sunitinib should be used with caution when co-administered with a drug with a known risk of Torsade de Pointes. In patients therapeutic doses of sunitinib have been shown to prolong the QTc interval. If coadministration is necessary, close monitoring including ECG assessment is recommended.

Coadministration has not been studied, but based on metabolism and clearance a clinically significant interaction is unlikely. Mycophenolate is mainly glucuronidated by UGT1A9 and 2B7. Sunitinib does not interact with this metabolic pathway. In addition, inhibition of OAT1/OAT3 renal transporters by mycophenolic acid (active metabolite) is unlikely to interfere with sunitinib elimination. However, due to the risk of additive haematological toxicity, haematological parameters should be monitored if coadministered.

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

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

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nateglinide is mainly metabolized by CYP2C9 (70%) and to a lesser extent CYP3A4 (30%). Sunitinib does not inhibit or induce CYPs.

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

Coadministration has not been studied and is not recommended. Nefazodone is metabolized mainly by CYP3A4 and is an inhibitor of CYP3A4. Nefazodone may increase sunitinib concentrations due to inhibition of CYP3A4. Concurrent use of CYP3A4 inhibitors should be avoided because sunitinib is relatively toxic and can cause dose-related QT-prolongation. If coadministration is unavoidable, monitor closely for sunitinib toxicity and reduce sunitinib dose in steps of 12.5 mg (25-33% dose reduction). For example, the dose of sunitinib may need to be reduced from 50 mg to 37.5 mg daily for GIST and MRCC in a 4/2 week intermittent scheme (25% dose reduction) and from 37.5 mg to 25 mg in a continuously daily dosing scheme for pNET, MRCC and GIST (33% dose reduction), based on careful monitoring of tolerability. Consider monitoring of sunitinib plasma concentrations, if available. ECG assessment is recommended.

Coadministration has not been studied. Nicardipine is metabolised mainly by CYP3A4 and to a lesser extent by CYP2D6 and 2C8. Sunitinib does not inhibit or induce CYPs. However, nicardipine inhibits CYP3A4 and could potentially increase sunitinib concentrations. No a priori dosage adjustment is recommended for sunitinib. Monitoring of sunitinib tolerability is recommended. 

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 metabolized by xanthine oxidase and aldehyde oxidase. Sunitinib does not interact with this metabolic pathway. In addition, nicotinic acid and its metabolites do not inhibit CYP-mediated reactions in vitro and therefore are unlikely to impact sunitinib exposure.

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

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nisoldipine is metabolized by CYP3A4. Sunitinib does not inhibit or induce CYPs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nitrendipine is extensively metabolized mainly by CYP3A4. Sunitinib does not inhibit or induce CYPs.

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

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). Sunitinib does not inhibit or induce CYPs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Norethisterone is extensively biotransformed, first by reduction and then by sulfate and glucuronide conjugation. Sunitinib does not interact with these metabolic pathways. 

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. Sunitinib does not interact with these metabolic pathways.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Norgestrel is a racemic mixture with levonorgestrel being biologically active. Levonorgestrel is mainly metabolized by CYP3A4. Sunitinib does not inhibit or induce CYPs.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Nortriptyline is metabolized mainly by CYP2D6. Sunitinib does not inhibit or induce CYPs. However, caution is needed when sunitinib is co-administered with a drug with a known risk of Torsade de Pointes. In patients, therapeutic doses of sunitinib have been shown to prolong the QTc interval. If coadministration is necessary, close monitoring including ECG assessment is recommended.

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. 

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Ofloxacin is eliminated unchanged renally by glomerular filtration and active tubular secretion via both cationic and anionic transport systems. Sunitinib is unlikely to interfere with this pathway. However, sunitinib should be used with caution when co-administered with a drug with a known risk of Torsade de Pointes. In patients therapeutic doses of sunitinib have been shown to prolong the QTc interval. If coadministration is necessary, close monitoring including ECG assessment is recommended.

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

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. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as omeprazole is unlikely to alter sunitinib absorption. Sunitinib is freely soluble from pH 1.2 to 6.8. Therefore, decreased absorption of sunitinib is not expected in combination with H2-antagonists and proton pump inhibitors. Moreover, omeprazole is mainly metabolised by CYP2C19 and in lesser extent by CYP3A4. Omeprazole induces CYP1A2 and inhibits CYP2C19. Sunitinib does not interact with this pathway. 

Coadministration has not been studied. Ondansetron is metabolized mainly by CYP1A2 and CYP3A4 and to a lesser extent by CYP2D6. Sunitinib does not inhibit of induce CYPs. However, ondansetron is substrate of P-gp and concentrations may potentially increase due to inhibition of P-gp by sunitinib. Moreover, ondansetron may prolong the QT interval dose dependently and sunitinib has been shown to prolong the QTc interval. Caution should be taken when using ondansetron with drugs that are known to prolong the QT interval. If coadministration is necessary, clinical monitoring including ECG assessment is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Oxazepam is mainly glucuronidated. Sunitinib does not interact with this metabolic pathway. 

Coadministration has not been studied but should be avoided as significant decreases in sunitinib plasma concentrations may occur due to induction of CYP3A4. If coadministration is clinically necessary, the product labels for sunitinib recommend a dose increase in 12.5 mg increments up to a maximum of 87.5 mg per day, based on careful monitoring of tolerability. Monitoring of sunitinib plasma concentrations should be considered, if available.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Oxprenolol is largely metabolized via glucuronidation. Sunitinib does not interact with this metabolic pathway. 

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. Sunitinib does not inhibit or induce CYPs. 

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 3A4. Sunitinib does not inhibit or induce CYPs.

Coadministration has not been studied. Palonosetron is metabolized mainly by CYP3A4 and to a lesser extent by CYP2D6 and CYP1A2. Sunitinib does not inhibit of induce CYPs. However, palonosetron is substrate of P-gp and concentrations may potentially increase due to inhibition of P-gp by sunitinib. The clinical relevance of this interaction is not known and monitoring may be required.

Osteonecrosis of the jaw has been reported in an increasing number of renal cell cancer patients since the use of combined therapies consisting of nitrogen-containing bisphosphonates and antiangiogenic targeted agents. This suggests that angiogenesis suppression might increase the risk of osteonecrosis of the jaw when coadministered with bisphosphonates. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as pantoprazole is unlikely to alter sunitinib absorption. Sunitinib is freely soluble from pH 1.2 to 6.8. Therefore, decreased absorption of sunitinib is not expected in combination with H2-antagonists and proton pump inhibitors. Moreover, pantoprazole is mainly metabolised by CYP2C19 and in lesser extent by CYP3A4, 2D6 and 2C9. Sunitinib does not interact with this pathway.

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. Sunitinib does not interact with this metabolic pathway. 

Coadministration has not been but based on metabolism and clearance a clinically significant interaction is unlikely. Paracetamol is mainly metabolized by glucuronidation (via UGT1A9 (major), UGT1A6, UGT1A1, UGT2B15) and sulfation and, to a lesser extent, by oxidation (CYP2E1 (major), 1A2, 3A4 and 2D6). There is no evidence that sunitinib inhibits or induces UGTs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Paroxetine is mainly metabolized by CYP2D6 and CYP3A4. Sunitinib does not inhibit or induce CYPs. 

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. However, coadministration may increase risk of neutropenia, fatigue, and thrombocytopenia. Monitor haematological parameters if used concurrently.

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). Sunitinib does not interfere with elimination of penicillins.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Perazine is demethylated via CYP3A4 and to a lesser extent by CYP2C9, and oxidated via FMO3. Sunitinib does not inhibit or induce CYPs.

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. Sunitinib does not inhibit or induce CYPs.

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 metabolized to other inactive metabolites. Elimination occurs predominantly via the urine. 

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Perphenazine is metabolized by CYP2D6. Sunitinib does not inhibit or induce CYPs. However, caution is needed when sunitinib is co-administered with a drug with a known risk of Torsade de Pointes. In patients, therapeutic doses of sunitinib have been shown to prolong the QTc interval. If coadministration is necessary, close monitoring including ECG assessment is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pethidine is metabolized mainly by CYP2B6 and to a lesser extent by CYP3A4. Sunitinib does not inhibit or induce CYPs. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Phenelzine is primarily metabolized by oxidation via monoamine oxidase and to a lesser extent acetylation. 

Coadministration has not been studied but should be avoided as significant decreases in sunitinib plasma concentrations may occur due to induction of CYP3A4. If coadministration is clinically necessary, the product labels for sunitinib recommend a dose increase in 12.5 mg increments up to a maximum of 87.5 mg per day, based on careful monitoring of tolerability. Monitoring of sunitinib plasma concentrations should be considered, if available.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Phenprocoumon is metabolised by CYP2C9 and CYP3A4. Sunitinib does not inhibit or induce CYPs. However increased risk of bleeding is possible with sunitinib in combination with coumarins. If coadministration is unavoidable, monitor closely for haemorrhage.

Coadministration has not been studied but should be avoided. Phenytoin is mainly metabolised by CYP2C9 and to a lesser extent by CYP2C19. Sunitinib does not inhibit or induce CYPs. However, phenytoin is a potent inducer of CYP3A4, UGT and P-gp. Concentrations of sunitinib may decrease due to induction of CYP3A4. Therefore, coadministration should be avoided. If coadministration is unavoidable, the dose of sunitinib may need to be increased in increments of 12.5 mg up to a maximum of 87.5 mg daily, with careful monitoring of tolerability. Consider monitoring of sunitinib plasma concentrations, if available.

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. Sunitinib does not interact with this metabolic pathway. 

Coadministration has not been studied and is contraindicated. Based on metabolism and clearance a pharmacokinetic interaction is unlikely as pimozide is mainly metabolized by CYP3A4 and sunitinib does not inhibit or induce CYPs. However, the product labels for pimozide contraindicate its use in the presence of other drugs that prolong the QT interval, such as sunitinib. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pindolol is partly metabolized to hydroxymetabolites (possibly via CYP2D6) and partly eliminated unchanged in the urine. Sunitinib is not expected to interfere with pindolol elimination. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pioglitazone is metabolized mainly by CYP2C8 and to a lesser extent by CYPs 3A4, 1A2 and 2C9. Sunitinib does not inhibit or induce CYPs.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. The metabolism of pipotiazine has not been well described but may involve CYP2D6. Sunitinib does not inhibit or induce CYPs. However, caution is needed when sunitinib is co-administered with a drug with a known risk of Torsade de Pointes. In patients, therapeutic doses of sunitinib have been shown to prolong the QTc interval. If coadministration is necessary, close monitoring including ECG assessment is recommended.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pitavastatin is metabolized by UGTs 1A3 and 2B7 with minimal metabolism by CYPs 2C9 and 2C8. Sunitinib does not interact with this metabolic pathway. 

Coadministration has not been studied and is not recommended as sunitinib concentrations may increase due to inhibition of CYP3A4 by posaconazole. Coadministration of sunitinib and ketoconazole increased total sunitinib plus active metabolite Cmax and AUC by 49% and 51%, respectively. The effect of posaconazole is expected to be comparable. Concurrent use of CYP3A4 inhibitors should be avoided, because sunitinib is relatively toxic and can cause dose-related QT-prolongation. If coadministration is unavoidable, monitor closely for sunitinib toxicity and reduce sunitinib dose in steps of 12.5 mg (25-33% dose reduction). For example, the dose of sunitinib may need to be reduced from 50 mg to 37.5 mg daily for GIST and MRCC in a 4/2 week intermittent scheme (25% dose reduction) and from 37.5 mg to 25 mg in a continuously daily dosing scheme for pNET, MRCC and GIST (33% dose reduction), based on careful monitoring of tolerability. Consider monitoring of sunitinib plasma concentrations, if available. ECG assessment is recommended.

Coadministration has not been studied but based on limited data available an interaction appears unlikely. Potassium is eliminated renally. 

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. Sunitinib does not inhibit or induce CYPs.

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

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Prednisolone undergoes hepatic metabolism via CYP3A4. Sunitinib does not inhibit or induce CYPs. 

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 metabolized by CYP3A4. Sunitinib does not inhibit or induce CYPs. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as pregabalin is cleared mainly by glomerular filtration.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Prochlorperazine is metabolised by CYP2D6 and CYP2C19. Sunitinib does not inhibit of induce CYPs. However, sunitinib should be used with caution when coadministered with a drug that has a potential risk to prolong the QT interval. Sunitinib has been shown to prolong the QT interval. If coadministration is necessary, clinical monitoring including ECG assessment is recommended.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Promethazine is metabolized by CYP2D6. Sunitinib does not inhibit or induce CYPs. However, caution is needed when sunitinib is co-administered with a drug with a known risk of Torsade de Pointes. In patients, therapeutic doses of sunitinib have been shown to prolong the QTc interval. If coadministration is necessary, close monitoring including ECG assessment is recommended.

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

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Prucalopride is minimally metabolised and mainly eliminated renally, partly by active secretion by renal transporters (of note no clinically relevant interactions were observed when prucalopride was coadministered with inhibitors of renal P-gp, OAT and OCT transporters). 

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

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Quetiapine is primarily metabolized by CYP3A4. Sunitinib does not inhibit or induce CYPs.

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. Sunitinib does not impact this renal transporter. 

Coadministration has not been studied. Sunitinib should be used with caution when co-administered with a drug with a known risk of Torsade de Pointes. In patients, therapeutic doses of sunitinib have been shown to prolong the QTc interval. If coadministration is necessary, close monitoring including ECG assessment is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as rabeprazole is unlikely to alter sunitinib absorption. Sunitinib is freely soluble from pH 1.2 to 6.8. Therefore, decreased absorption of sunitinib is not expected in combination with H2-antagonists and proton pump inhibitors. Moreover, rabeprazole is mainly metabolised via non-enzymatic reduction and in lesser extent by CYP2C19 and 3A4. Sunitinib does not interact with this pathway.

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 metabolized to the diketopiperazine ester, diketopiperazine acid and the glucuronides of ramipril and ramiprilat. Sunitinib is not expected to interact with these metabolic pathways. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as ranitidine is unlikely to alter sunitinib absorption. Sunitinib is freely soluble from pH 1.2 to 6.8. Therefore, decreased absorption of sunitinib is not expected in combination with H2-antagonists and proton pump inhibitors.

Coadministration has not been studied but should be approached with caution. Ranolazine is primarily metabolised by CYP3A4 and to a lesser extent by CYP2D6. Ranolazine is also a substrate of P-gp. Sunitinib is an inhibitor of P-gp and may increase concentrations of ranolazine. Furthermore, ranolazine is a weak inhibitor of P-gp, CYP3A4 and CYP2D6. Ranolazine could potentially increase sunitinib concentrations due to CYP3A4 inhibition. The clinical relevance of this interaction is unknown. No a priori dosage adjustment is recommended. However, caution is warranted when coadministering these drugs due to the risk of QT interval prolongation. If coadministration is necessary, close monitoring including ECG assessment is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Reboxetine is metabolized by CYP3A4. In vitro data indicate reboxetine to be a weak inhibitor of CYP3A4 but in vivo data showed no inhibitory effect on CYP3A4. Sunitinib does not interact with reboxetine metabolic pathway. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Repaglinide is metabolized by CYP2C8 and 3A4 and clinical data seem to indicate that it is a substrate of the hepatic transporter OATP1B1. Sunitinib does not interact with this metabolic pathways.

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. Retinol not stored in the liver undergoes glucuronide conjugation and subsequent oxidation to retinal and retinoic acid. Sunitinib does not interact with this metabolic pathway. 

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

Coadministration has not been studied but should be avoided as significant decreases in sunitinib plasma concentrations may occur due to induction of CYP3A4. If coadministration is clinically necessary, the product labels for sunitinib recommend a dose increase in 12.5 mg increments (up to 87.5 mg per day for GIST and MRCC or 62.5 mg per day for pNET), based on careful monitoring of tolerability. Monitoring of sunitinib plasma concentrations should be considered, if available.

Coadministration should be avoided as significant decreases in sunitinib plasma concentrations occur due to induction of CYP3A4. Coadministration of sunitinib and rifampicin decreased sunitinib Cmax and AUC by 23% and 46%, respectively. If coadministration is clinically necessary, the product labels for sunitinib recommend a dose increase in 12.5 mg increments (up to 87.5 mg per day for GIST and MRCC or 62.5 mg per day for pNET), based on careful monitoring of tolerability. Monitoring of sunitinib plasma concentrations should be considered, if available.

Coadministration has not been studied but should be avoided as significant decreases in sunitinib plasma concentrations may occur due to induction of CYP3A4. If coadministration is clinically necessary, the product labels for sunitinib recommend a dose increase in 12.5 mg increments (up to 87.5 mg per day for GIST and MRCC or 62.5 mg per day for pNET), based on careful monitoring of tolerability. Monitoring of sunitinib plasma concentrations should be considered, if available.

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. Sunitinib does not interact with this metabolic pathway. 

Coadministration has not been studied. Risperidone is metabolized by CYP2D6 and to a lesser extent by CYP3A4. Sunitinib does not inhibit or induce CYPs. However, risperidone is a substrate of P-gp and concentrations may potentially increase due to inhibition of P-gp by sunitinib. The clinical relevance of this interaction is unknown and monitoring may be required.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Rivaroxaban is partly metabolized in the liver (by CYP3A4, CYP2J2 and hydrolytic enzymes) and partly eliminated unchanged in urine (by P-gp and BCRP). Increases in rivaroxaban plasma concentrations cannot be excluded via of inhibition of P-gp. The clinical relevance of this interaction is not known and monitoring may be required.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Rosiglitazone is metabolized mainly by CYP2C8 and to a lesser extent 2C9. Sunitinib does not inhibit or induce CYPs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as rosuvastatin is largely excreted unchanged via the faeces. 

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Salmeterol is metabolized by CYP3A4. Sunitinib does not inhibit or induce CYPs.

Coadministration has not been studied. Saxagliptin is mainly metabolized by CYP3A4 and is a substrate of P-gp. Saxagliptin concentrations may potentially increase due to inhibition of P-gp by sunitinib. Monitoring may be required.

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 drug interactions are known. 

Coadministration has not been studied and is contraindicated. Based on metabolism and clearance a pharmacokinetic interaction is unlikely as sertindole is metabolized by CYP2D6 and CYP3A4 and sunitinib does not inhibit or induce CYPs. However, the product labels for sertindole contraindicate its use in the presence of other drugs that prolong the QT interval, such as sunitinib.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Sertraline is mainly metabolized by CYP2B6 and to a lesser extent by CYPs 2C9, 2C19, 2D6 and 3A4. Sunitinib does not inhibit or induce CYPs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Sildenafil is metabolized mainly by CYP3A4 and to a lesser extent by CYP2C9. Sunitinib does not inhibit or induce CYPs. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Simvastatin is metabolized by CYP3A4. Sunitinib does not inhibit or induce CYPs. 

Coadministration has not been studied. Sirolimus is metabolized by CYP3A4 and is substrate of P-gp. Sunitinib does not inhibit or induce CYPs, but may possibly increase sirolimus concentrations by inhibition of P-gp. A study of temsirolimus (the water soluble ester of sirolimus) and sunitinib showed dose limiting toxicities even at low doses. Use with caution and with close monitoring for adverse effects. Due to the risk of additive haematological toxicity, haematological parameters should be monitored if coadministered.

Coadministration has not been studied. Sitagliptin is primarily eliminated in urine as unchanged drug (active secretion by OAT3, OATP4C1, P-gp) and metabolism by CYP3A4 represents a minor elimination pathway. Sitagliptin concentrations may potentially increase due to inhibition of P-gp by sunitinib. Monitoring may be required.

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. There is little potential for sodium nitroprusside to affect the disposition of sunitinib, or to be affected if co-administered with sunitinib. 

Coadministration has not been studied and is not recommended. Based on metabolism and clearance a pharmacokinetic interaction is unlikely as sotalol is excreted unchanged via renal elimination. However, coadministration is not recommended due to the potential of life threatening arrhythmias such as torsade de pointes and sudden death. The product labels for sotalol advise extreme caution if given with other drugs that prolong the QT interval, such as sunitinib. 

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. Sunitinib does not interact with this metabolic pathway. 

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

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

Coadministration has not been studied and should be avoided. St John’s wort may cause significant and unpredictable decreases in the plasma concentrations of sunitinib due to induction of CYP3A4 and P-gp.

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. Streptokinase is unlikely to affect the disposition of tyrosine kinase inhibitors, or to be affected if coadministered with tyrosine kinase inhibitors.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as streptomycin is eliminated by glomerular filtration.

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. Sunitinib does not interfere with sulfadiazine metabolism.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Sulpiride is mainly excreted in the urine and faeces as unchanged drug. However, caution is needed when sunitinib is co-administered with a drug with a known risk of Torsade de Pointes. In patients, therapeutic doses of sunitinib have been shown to prolong the QTc interval. If coadministration is necessary, close monitoring including ECG assessment is recommended.

Coadministration has not been studied. Sunitinib is metabolised mainly by CYP3A4. Tacrolimus inhibits CYP3A4 and OATP1B1 in vitro but produced modest inhibition of CYP3A4 and OATP1B1 in the range of clinical concentrations. Tacrolimus could potentially increase sunitinib concentrations although to a modest extent. No a priori dosage adjustment is recommended. In addition, sunitinib inhibits P-gp and may possibly increase tacrolimus concentrations. Moreover, caution is needed when co-administering sunitinib with a drug with a known risk of Torsade de Pointes. In patients, therapeutic doses of sunitinib have been shown to prolong the QTc interval. If coadministration is necessary, close monitoring including ECG assessment is recommended. Due to the risk of additive haematological toxicity, haematological parameters should be monitored if coadministered.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as tadalafil is metabolized by CYP3A4. Sunitinib does not inhibit or induce CYPs. 

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. Sunitinib does not inhibit or induce CYPs. 

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. Sunitinib does not interact with this elimination pathway.

Coadministration has not been studied but may increase sunitinib concentrations due to inhibition of CYP3A4 by telithromycin. Concurrent use of CYP3A4 inhibitors should be avoided because sunitinib is relatively toxic and can cause dose-related QT-prolongation. If coadministration is unavoidable, monitor closely for sunitinib toxicity and reduce sunitinib dose in steps of 12.5 mg (25-33% dose reduction). For example, the dose of sunitinib may need to be reduced from 50 mg to 37.5 mg daily for GIST and MRCC in a 4/2 week intermittent scheme (25% dose reduction) and from 37.5 mg to 25 mg in a continuously daily dosing scheme for pNET, MRCC and GIST (33% dose reduction), based on careful monitoring of tolerability. Consider monitoring of sunitinib plasma concentrations, if available. ECG assessment is recommended. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Telmisartan is mainly glucuronidated by UGT1A3. Sunitinib does not interact with this metabolic pathway. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Temazepam is mainly glucuronidated. Sunitinib does not interact with this metabolic pathway. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Terbinafine is metabolized by CYPs 1A2, 2C9, 3A4 and to a lesser extent by CYPs 2C8 and 2C19. Sunitinib does not inhibit or induce CYPs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Testosterone is metabolized by CYP3A4. Sunitinib does not inhibit or induce CYPs. 

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.

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

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

Coadministration has not been studied and is contraindicated. Based on metabolism and clearance a pharmacokinetic interaction is unlikely as thioridazine is metabolized by CYP2D6 (and to a lesser extent by CYP3A4) and sunitinib does not inhibit or induce CYPs. However, the product labels for thioridazine contraindicate its use in the presence of other drugs that prolong the QT interval, such as sunitinib. 

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely as tiapride is excreted largely unchanged in urine. However, caution is needed when sunitinib is co-administered with a drug with a known risk of Torsade de Pointes. In patients, therapeutic doses of sunitinib have been shown to prolong the QTc interval. If coadministration is necessary, close monitoring including ECG assessment is recommended.

Coadministration has not been studied. Ticagrelor undergoes extensive CYP3A4 metabolism and is only a mild inhibitor of CYP3A4. Ticagrelor is unlikely to be affected if co-administered with sunitinib. However, sunitinib concentrations may be slightly increased if co-administered with ticagrelor. The clinical relevance of this interaction is not known and monitoring may be required.

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. Sunitinib does not inhibit or induce CYPs.

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. Sunitinib does not interact with this elimination pathway.