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 microbial flora. 

Coadministration has not been studied. Acenocoumarol is mainly metabolised by CYP2C9 and to a lesser extent by CYP1A2 and CYP2C19. Nilotinib is a moderate inhibitor of CYP2C19 and CYP2C9 in vitro. Concentrations of acenocoumarol may increase due to inhibition of CYP2C9 and CYP2C19 by nilotinib. Although the clinical relevance of this interaction is unknown, it is recommended to closely monitor INR in the case of coadministration.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Aspirin is rapidly deacetylated to form salicylic acid and then further metabolised by glucuronidation (by several UGT, major UGT1A6). Nilotinib does not inhibit or induce UGT1A6.

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

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

Coadministration has not been studied. Alfentanil undergoes extensive CYP3A4 metabolism. Nilotinib is a weak inhibitor of CYP3A4 and may increase concentrations of alfentanil. As the clinical relevance of this interaction is unknown, monitoring of toxicity may be required. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Alfuzosin is metabolised by CYP3A4. Nilotinib is a weak inhibitor of CYP3A4 and may increase concentrations of alfuzosin. However, since alfuzosin has a wide therapeutic index, a clinically relevant interaction is unlikely.

Coadministration has not been studied. Aliskiren is minimally metabolised and is mainly excreted unchanged in faeces. P-gp is a major determinant of aliskiren bioavailability. Nilotinib is an inhibitor of P-gp in vitro. Concentrations of aliskiren may increase due to inhibition of P-gp by nilotinib. Monitoring of blood pressure is recommended when nilotinib is coadministered with aliskiren.

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. Nilotinib 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 data indicate that alosetron is metabolised by CYPs 2C9, 3A4 and 1A2. Nilotinib is a potent inhibitor of CYP3A4 in vitro but only a weak inhibitor in vivo; it also potently inhibits CYP2C9 in vitro but the in vivo effect has yet to be determined. However, due to the wide therapeutic index of alosetron, this interaction is unlikely to be clinically relevant.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Alprazolam is mainly metabolised by CYP3A4. Nilotinib is a weak inhibitor of CYP3A4 and may increase concentrations of alprazolam. However, since alprazolam does not have a narrow therapeutic index, a clinically relevant interaction is unlikely.

The solubility of nilotinib is pH dependent. Coadministration with antacids showed no significant change in nilotinib pharmacokinetics when the antacid dose was administered 2 hours before or after nilotinib. Therefore, when concurrent use of an antacid is necessary, it may be administered 2 hours before and 2 hours after the dose of nilotinib. Monitoring may be required.

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. Nilotinib is a strong inhibitor of CYP3A4 in vitro but only a weak inhibitor in vivo; it is a moderate inhibitor of CYP2C19 in vitro but the in vivo effect has yet to be determined. Since CYP3A4 and CYP2C19 mediated metabolism are minor pathways, this is unlikely to be clinically relevant. However, ambrisentan is also a substrate of P-gp. Nilotinib is a weak inhibitor of P-gp and may increase concentrations of ambrisentan. As the clinical relevance of this interaction is unknown, monitoring for ambrisentan toxicity may be required.

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

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. Nilotinib is unlikely to affect amiloride renal elimination.

Coadministration has not been studied but should be approached with caution. Amiodarone is metabolised by CYP3A4 and CYP2C8. Concentrations of amiodarone may increase due to weak inhibition of CYP3A4 by nilotinib. The clinical relevance of this interaction is unknown. Care should be taken when nilotinib is coadministered with substrates of CYP3A4 with a narrow therapeutic index such as amiodarone. Moreover, the major metabolite of amiodarone, desethylamiodarone, is an inhibitor of CYP3A4 (weak), CYP2C9 (moderate), CYP2D6 (moderate), CYP2C19 (weak), CYP1A1 (strong), CYP2B6 (moderate) and P-gp (strong). Concentrations of nilotinib may increase due to P-gp inhibition. Selection of an alternate concomitant medication with no or minimal potential to inhibit P-gp is recommended. Furthermore use nilotinib with caution when coadministering with a drug with a known risk of Torsade de Pointes such as amiodarone. If coadministration is necessary, close monitoring including ECG assessment is recommended. Note: due to the long half-life of amiodarone, interactions can be observed for several months after discontinuation of amiodarone.

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

Coadministration has not been studied. Amitriptyline is metabolised predominantly by CYP2D6 and CYP2C19. Nilotinib is a moderate inhibitor of CYP2C19 in vitro but the in vivo effect has yet to be determined. Although clinically relevant CYP2C19 mediated interactions are unlikely, monitoring may be required. Furthermore, use nilotinib with caution when coadministered with a drug with a known risk of Torsade de Pointes. In patients, therapeutic doses of nilotinib have been shown to prolong the QTc interval. If coadministration is necessary, close monitoring including ECG assessment is recommended.

Coadministration has not been studied. Amlodipine is metabolised by CYP3A4. Nilotinib is a weak inhibitor of CYP3A4 and may increase concentrations of amlodipine. As the clinical relevance of this interaction is unknown, monitoring of blood pressure is recommended.

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. Nilotinib 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 metabolised and is eliminated to a large extent in the bile. Nilotinib does not interfere with amphotericin B elimination pathway. However, amphotericin B has a possible risk of QT interval prolongation. Therefore, use nilotinib with caution when coadministered with amphotericin B. In patients, therapeutic doses of nilotinib 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 20-40% of an oral dose may be excreted unchanged in the urine in 6 hours. After parenteral use about 60-80% is excreted in the urine within 6 hours. Nilotinib 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 temperatures. 

The solubility of nilotinib is pH dependent. Coadministration with antacids showed no significant change in nilotinib pharmacokinetics when the antacid dose was administered 2 hours before or after nilotinib. Therefore, when concurrent use of an antacid is necessary, it may be administered 2 hours before and 2 hours after the dose of nilotinib. Monitoring may be required.

Coadministration has not been studied. Apixaban is transported by P-gp and is metabolised predominantly by CYP3A4, and to a lesser extent by CYPs 1A2, 2C8, 2C9 and 2C19. Nilotinib is a weak inhibitor of CYP3A4 and P-gp and inhibits CYP2C8 and CYP2C9 in vitro, potentially increasing concentrations of apixaban. As the clinical relevance of this interaction is unknown, close monitoring may be required.

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. Nilotinib is an inhibitor of CYP3A4 and CYP2C9 (in vitro), and may increase concentrations of aprepitant. Furthermore, during treatment aprepitant is a moderate inhibitor of CYP3A4 and may increase concentrations of nilotinib during the three days of coadministration. Therefore, coadministration is not recommended. If coadministration is unavoidable, reduce the nilotinib dose to 50% of the original dose during the few days of coadministration. Monitor closely for nilotinib toxicity. After treatment, aprepitant is a weak inducer of CYP3A4, CYP2C9 and UGT. Concentrations of nilotinib 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 pharmacokinetic interaction is unlikely. Aripiprazole is metabolised by CYP3A4 and CYP2D6. Nilotinib is a potent inhibitor of CYP3A4 in vitro but only a weak inhibitor in vivo; it is a moderate inhibitor of CYP2D6 in vitro but the in vivo effect has yet to be determined. As the clinical relevance of these interactions is unknown, monitoring may be required.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Asenapine is metabolised by glucuronidation (UGT1A4) and oxidative metabolism (CYPs 1A2 (major), 3A4 and 2D6 (minor)). Nilotinib is a weak inhibitor of CYP3A4; it is also a moderate inhibitor of CYP2D6 in vitro but the in vivo effect has yet to be determined. However since these are minor pathways, a clinically relevant interaction is unlikely.

Coadministration has not been studied and is not recommended. Astemizole is metabolised by CYPs 2D6, 2J2 and 3A4. Nilotinib is a potent inhibitor of CYP3A4 in vitro but only a weak inhibitor in vivo; it is a moderate inhibitor of CYP2D6 in vitro but the in vivo effect has yet to be determined. As the clinical relevance of these interactions is unknown, monitoring may be required. Furthermore, use nilotinib with caution when coadministered with a drug with a known risk of Torsade de Pointes. In patients, therapeutic doses of nilotinib 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. Atorvastatin is metabolised by CYP3A4 and is a substrate of P-gp and OATP1B1. Nilotinib is a weak inhibitor of CYP3A4 and an inhibitor of P-gp in vitro, potentially increasing concentrations of atorvastatin. As a clinically relevant interaction is unknown, monitoring for toxicity may be required.

Coadministration has not been studied. Azathioprine is converted to 6-mercaptopurine which is metabolised analogously to natural purines. Nilotinib 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 but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Azithromycin is mainly eliminated via biliary excretion with animal data suggesting this may occur via P-gp and MRP2. Nilotinib does not interact with this pathway and no effect on nilotinib concentrations is expected. However, use azithromycin with caution when coadministered with drugs that are known to prolong the QT interval. In patients, therapeutic doses of nilotinib have been shown to prolong the QTc interval with approximately 20 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. 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. Nilotinib does not interact with this pathway. 

Coadministration has not been studied. Bedaquiline is metabolised by CYP3A4. Nilotinib is a weak inhibitor of CYP3A4 and may increase bedaquiline concentrations. The clinical relevance of this interaction is unknown. Bedaquiline prolongs the QTc interval and if coadministered with nilotinib 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 nilotinib inhibits these renal transporters but a clinically relevant 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 nilotinib.

Coadministration has not been studied. Bepridil is metabolised by CYP2D6 (major) and CYP3A4. Nilotinib is a potent inhibitor of CYP3A4 in vitro but only a weak inhibitor in vivo; it is a moderate inhibitor of CYP2D6 in vitro but the in vivo effect has yet to be determined. Although clinically relevant CYP2D6 mediated interactions are unlikely, monitoring for toxicity may be required. Furthermore, use nilotinib with caution when coadministering with a drug with a known risk of Torsade de Pointes. In patients, therapeutic doses of nilotinib have been shown to prolong the QTc interval with approximately 20 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. Betamethasone is metabolised by CYP3A4. Nilotinib is a weak inhibitor of CYP3A4 and may increase concentrations of betamethasone. However, since betamethasone has a wide therapeutic index, a clinically relevant interaction is unlikely.

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. Nilotinib does not interact with this pathway.

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 metabolised by CYP3A4 and CYP2D6 and partly eliminated unchanged in the urine. Nilotinib is a potent inhibitor of CYP3A4 in vitro but only a weak inhibitor in vivo; it is a moderate inhibitor of CYP2D6 in vitro but the in vivo effect has yet to be determined. Although clinically relevant CYP2D6 interactions are unlikely, monitoring of blood pressure is recommended.

Coadministration has not been studied. Bosentan is a substrate and inducer of CYP3A4 and CYP2C9 and could potentially decrease nilotinib exposure. Nilotinib is a potent inhibitor of CYP3A4 in vitro but only a weak inhibitor in vivo; it also potently inhibits CYP2C9 in vitro but the in vivo effect has yet to be determined. As the clinical relevance of these interactions is unknown, close monitoring of nilotinib plasma concentrations is recommended, if available.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bromazepam undergoes oxidative biotransformation. Data indicate that CYP3A4 plays a minor role in bromazepam metabolism, but other cytochromes such as CYP2D6 or CYP1A2 may also play a role. Nilotinib is a potent inhibitor of CYP3A4 in vitro but only a weak inhibitor in vivo; it is a moderate inhibitor of CYP2D6 in vitro but the in vivo effect has yet to be determined. However, since bromazepam does not have a narrow therapeutic index, a clinically relevant interaction is unlikely.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Budesonide is metabolised by CYP3A4. Nilotinib is a weak inhibitor of CYP3A4 and may increase concentrations of budesonide. However, since betamethasone has a wide therapeutic index, a clinically relevant interaction is unlikely.

Coadministration has not been studied. Buprenorphine undergoes both N-dealkylation to form norbuprenorphine (via CYP3A4) and glucuronidation (via UGT2B7 and UGT1A1). Nilotinib is a weak CYP3A4 inhibitor and an inhibitor of UGT1A1 in vitro. As the clinical relevance of these interactions is unknown, monitoring for toxicity may be required. 

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Buspirone is metabolised by CYP3A4. Nilotinib is a weak inhibitor of CYP3A4 and may increase concentrations of buspirone. However, since buspirone does not have a narrow therapeutic index, a clinically relevant interaction is unlikely.

Coadministration has not been studied but a clinically significant 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. Nilotinib 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. Nilotinib 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. Nilotinib is an inhibitor of CYP3A4 (weak, in vivo) and CYP2C8 (in vitro) and may increase carbamazepine concentrations. The clinical relevance of this interaction is unknown. Furthermore, carbamazepine is an inducer of CYPs 2C8 (strong), 2C9 (strong), 3A4 (strong), 1A2 (weak), 2B6 and UGT1A1. Significant decreases in nilotinib plasma exposure may occur due to induction of CYP3A4. Decreased nilotinib exposure can lead to decreased efficacy. Selection of an alternative concomitant medication with no or minimal enzyme or transporter induction potential is recommended. If coadministration is unavoidable, the dose of nilotinib may need increasing depending on patient tolerability. No absolute dose adjustment advice can be given, due to the non-linear pharmacokinetics. A dosing regimen more frequent than twice daily may be necessary to obtain adequate nilotinib exposure. Consider monitoring of nilotinib plasma concentrations, 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. Nilotinib is a potent inhibitor of CYP2C9 in vitro but the in vivo effect has yet to be determined; it is a moderate inhibitor of CYP2D6 and UGT1A1 in vitro but again, the in vivo effect has yet to be determined. Although clinically relevant CYP2D6 interactions are unlikely, monitoring of blood pressure is recommended.

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. Nilotinib does not interact with this metabolic pathway. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nilotinib is predominantly renally eliminated unchanged by glomerular filtration and tubular secretion via OAT1 and MATE1. Nilotinib 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. Nilotinib 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. Nilotinib 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 metabolised by non-specific esterases. Most of a dose of cefotaxime is excreted in the urine - about 60% as unchanged drug and a further 24% as desacetyl-cefotaxime, an active metabolite. In vitro studies indicate that OAT3 participates in the renal elimination of cefotaxime. Nilotinib 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. Nilotinib 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. Nilotinib does not interfere with ceftriaxone renal elimination.

Coadministration has not been studied. Celecoxib is primarily metabolised by CYP2C9. Nilotinib is an inhibitor of CYP2C9 in vitro and may increase concentrations of celecoxib. As the clinical relevance of this interaction is unknown, monitoring for toxicity may be required. 

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. Nilotinib 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 nilotinib via this mechanism, increasing the risk of adverse events. Although the clinical significance of this interaction is unknown, 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. Chlordiazepoxide is extensively metabolised by CYP3A4, but does not inhibit or induce cytochromes. Nilotinib is a weak inhibitor of CYP3A4 and may increase chlordiazepoxide concentrations. 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. Chlorphenamine is predominantly metabolised in the liver via CYP2D6. Nilotinib is a moderate inhibitor of CYP2D6 in vitro but the in vivo effect has yet to be determined. However, clinically relevant CYP2D6 mediated interactions are unlikely.

Coadministration has not been studied. Chlorpromazine is metabolised mainly by CYP2D6, but also by CYP1A2. Nilotinib is a moderate inhibitor of CYP2D6 in vitro but the in vivo effect has yet to be determined. However, clinically relevant CYP2D6 mediated interactions are unlikely. Use nilotinib with caution when coadministered with a drug with a known risk of Torsade de Pointes. In patients, therapeutic doses of nilotinib 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, potentially increasing nilotinib concentrations. Nilotinib is a weak inhibitor of CYP3A4 and P-gp and may increase ciclosporin exposure. The clinical relevance of this interaction is unknown. No a priori dosage adjustment is recommended for nilotinib and ciclosporin, but close monitoring of 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. Cilazapril is mainly eliminated unchanged by the kidneys. 

Coadministration has not been studied. The solubility of nilotinib is pH dependent. No significant change in nilotinib pharmacokinetics was observed when nilotinib was administered 10 hours after and 2 hours before famotidine. Therefore, when the concurrent use of a H2 receptor antagonist is necessary, it may be administered approximately 10 hours before and approximately 2 hours after the dose of nilotinib. Although, use of proton pump inhibitors or H2 antagonists did not seem to affect the efficacy of nilotinib in patients with Ph+ CML-CP, monitoring of nilotinib plasma concentrations should be considered, if available.

Coadministration has not been studied but should be approached with caution. 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. Nilotinib does not interfere with the elimination of ciprofloxacin. However, ciprofloxacin is a weak to moderate inhibitor of CYP3A4 and a strong inhibitor of CYP1A2. Concentrations of nilotinib may increase due to inhibition of CYP3A4. Concurrent use of CYP3A4 inhibitors should be avoided as nilotinib is relatively toxic. If coadministration is unavoidable, a decrease of the nilotinib dose to 50% of the original dose should be considered. However, there are no clinical data supporting this recommended dose adjustment in patients receiving CYP3A4 inhibitors. In addition, caution should be taken when using ciprofloxacin with drugs that are known to prolong the QT interval. In patients, therapeutic doses of nilotinib 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. Nilotinib is a weak inhibitor of CYP3A4 and may increase concentrations of cisapride. The clinical relevance of this interaction is unknown. However, nilotinib should be used with caution when co-administered with a drug with a known risk of Torsade de Pointes. 

Coadministration has not been studied. Citalopram is metabolised by CYPs 2C19 (38%), 2D6 (31%) and 3A4 (31%). Nilotinib is a potent inhibitor of CYP3A4 in vitro but only a weak inhibitor in vivo; it is a moderate inhibitor of CYP2C19 and CYP2D6 in vitro but the in vivo effect has yet to be determined. Although clinically relevant CYP2C19 and CYP2D6 mediated interactions are unlikely, monitoring may be required. Furthermore, use nilotinib with caution when coadministered with a drug with a known risk of Torsade de Pointes. In patients, therapeutic doses of nilotinib have been shown to prolong the QTc interval. If coadministration is necessary, close monitoring including ECG assessment is recommended.

Coadministration has not been studied. Clarithromycin may increase nilotinib concentrations due to inhibition of CYP3A4 and P-gp. Concurrent use of potent CYP3A4 inhibitors should be avoided as nilotinib is relatively toxic and can cause QT-prolongation. If coadministration is clinically necessary, the product labels for nilotinib recommend a dose reduction of 50%. However, there are no clinical data with this dose adjustment in patients receiving CYP3A4 inhibitors. Monitoring of nilotinib plasma concentrations should be considered, if available. 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. Clavulanic acid is extensively metabolised (likely non CYP mediated pathway) and excreted in the urine by glomerular filtration. Nilotinib does not interact with this metabolic pathway. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clemastine is predominantly metabolised in the liver via CYP2D6. Nilotinib is a moderate inhibitor of CYP2D6 in vitro but the in vivo effect has yet to be determined. A clinically relevant interaction is unlikely since clemastine has a wide therapeutic index. 

Coadministration has not been studied. Clindamycin is metabolised by CYP3A4. Nilotinib is a weak inhibitor of CYP3A4 and may increase clindamycin concentrations. 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 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 nilotinib have been shown to prolong the QTc interval with approximately 20 msec. 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 hydrolysed to an active metabolite, clofibric acid. Excretion of clofibric acid glucuronide is possibly performed via OAT1. Nilotinib does not interfere with clofibrate elimination.

Coadministration has not been studied. Clomipramine is metabolised by CYPs 3A4, 1A2 and 2C19 to desmethylclomipramine, an active metabolite which has a higher activity than the parent drug. In addition, clomipramine and desmethylclomipramine are metabolised by CYP2D6. Nilotinib is a potent inhibitor of CYP3A4 in vitro but only a weak inhibitor in vivo; it is a moderate inhibitor of CYP2C19 and CYP2D6 in vitro but the in vivo effect has yet to be determined. Although clinically relevant CYP2C19 and CYP2D6 mediated interactions are unlikely, monitoring may be required. Furthemore, use nilotinib with caution when coadministered with a drug with a known risk of Torsade de Pointes. In patients, therapeutic doses of nilotinib 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 the form of the unchanged parent drug (40-60% of the dose). Nilotinib does not interfere with clonidine elimination. Furthermore, clonidine is a weak inhibitor of OCT2. Nilotinib is not a substrate of OCT2 and therefore clonidine is unlikely to interact with nilotinib 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. Nilotinib is a potent inhibitor of CYP3A4 in vitro but only a weak inhibitor in vivo; it is a moderate inhibitor of CYP2C19 in vitro but the in vivo effect has yet to be determined. Although clinically relevant CYP2C19 mediated interactions are unlikely, monitoring may be required.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clorazepate is rapidly converted to nordiazepam which is then metabolised to oxazepam by CYP3A4. Nilotinib is a weak inhibitor of CYP3A4 and may increase concentrations of clorazepate. However, since clorazepate does not have a narrow therapeutic index, a clinically relevant interaction is unlikely.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cloxacillin is metabolised to a limited extent, and the unchanged drug and metabolites are excreted in the urine by glomerular filtration and renal tubular secretion. Nilotinib does not interact with this metabolic pathway.

Coadministration has not been studied but should be approached with caution. Clozapine is metabolised mainly by CYP1A2 and CYP3A4, and to a lesser extent by CYP2C19 and CYP2D6. Nilotinib is a potent inhibitor of CYP3A4 in vitro but only a weak inhibitor in vivo. Therefore, clozapine concentrations may slightly increase. Furthermore, nilotinib is also a moderate inhibitor of CYP2D6 and CYP2C19 in vitro but the in vivo effect has not yet been determined. Since CYP2D6 and CYP2C19 represent only minor pathways, clinically relevant interactions are unlikely. However, use nilotinib with caution when coadministered with a drug with a known risk of Torsade de Pointes. In patients, therapeutic doses of nilotinib 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 also 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. Nilotinib 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. Nilotinib is a weak inhibitor of CYP3A4 and inhibits CYP2D6 in vitro. Concentrations of codeine may increase due to inhibition of CYP2D6 and CYP3A4, and thus concentrations of morphine may decrease due to inhibition of CYP2D6. Therefore the analgesic effect of codeine may be reduced. Monitoring of codeine and morphine efficacy may be required.

Coadministration has not been studied. Colchicine is metabolised by CYP3A4 and transported by P-gp. Nilotinib is a weak inhibitor of CYP3A4 and P-gp, potentially increasing concentrations of colchicine. As the clinical relevance of this interaction is unknown, monitoring for colchicine toxicity may be required.

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

Coadministration has not been studied. Dabigatran is transported by P-gp and is renally excreted. Nilotinib 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 and based on metabolism and clearance a clinically significant interaction is unlikely. Dalteparin is excreted largely unchanged via the kidneys. Nilotinib does not interfere with this pathway. 

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. Nilotinib is a potent inhibitor of CYP3A4 in vitro but only a weak inhibitor in vivo; it is also a moderate inhibitor of CYP2D6 and CYP2C19 in vitro but the in vivo effect has yet to be determined. However, clinically relevant CYP2D6 and CYP2C19 mediated interactions are unlikely.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely as desipramine is metabolised by CYP2D6. Nilotinib is a moderate inhibitor of CYP2D6 in vitro but the in vivo effect has yet to be determined. Although clinically relevant CYP2D6 mediated interactions are unlikely, monitoring may be required. Furthermore, use nilotinib with caution when coadministered with a drug with a known risk of Torsade de Pointes. In patients, therapeutic doses of nilotinib have been shown to prolong the QTc interval. If coadministration is necessary, close monitoring including ECG assessment is recommended.

Coadministration has not been studied. Desogestrel is a prodrug which is activated to etonogestrel by CYP2C9 (and possibly CYP2C19); the metabolism of etonogestrel is mediated by CYP3A4. Nilotinib is a potent inhibitor of CYP3A4 in vitro but only a weak inhibitor in vivo; it also potently inhibits CYP2C9 in vitro but the in vivo effects are yet to be determined. Furthermore, nilotinib is a moderate inhibitor of CYP2C19 in vitro but again, the in vivo effect has yet to be determined. Although clinically relevant CYP2C19 and CYP2C9 mediated interactions are unlikely, monitoring may be required.

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

Coadministration has not been studied. Dextropropoxyphene is mainly metabolised by CYP3A4. Nilotinib is a weak inhibitor of CYP3A4 and may increase concentrations of dextropropoxyphene. As the clinical relevance of this interaction is unknown, monitoring for toxicity may be required. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Diamorphine is rapidly metabolised by sequential deacetylation to morphine which is then mainly glucuronidated to morphine-3-glucuronide (UGT2B7>UGT1A1) and to a lesser extent, to the pharmacologically active morphine-6-glucuronide (UGT2B7>UGT1A1). Nilotinib is an inhibitor of UGT1A1 in vitro but since UGT1A1 mediated metabolism is only a minor pathway, a clinically relevant interaction is unlikely.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Diazepam is metabolised to nordiazepam (by CYP3A4 and CYP2C19) and to temazepam (mainly by CYP3A4). Nilotinib is a weak inhibitor of CYP3A4 and may increase concentrations of diazepam. However, since diazepam does not have a narrow therapeutic index, a clinically relevant interaction is unlikely.

Coadministration has not been studied. Diclofenac is partly glucuronidated by UGT2B7 and partly oxidised by CYP2C9. Nilotinib is an inhibitor of CYP2C9 in vitro and may increase concentrations of diclofenac. As the clinical relevance of this interaction is unknown, monitoring for toxicity may be required.

Coadministration has not been studied. Digoxin is renally eliminated via the renal transporters OATP4C1 and P-gp. Nilotinib is an inhibitor of P-gp in vitro but the in vivo effect has yet to be determined. Concentrations of digoxin may increase due to inhibition of P-gp by nilotinib. Close monitoring for digoxin toxicity is recommended when nilotinib is coadministered and monitoring of digoxin plasma concentrations should also be considered.

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. Nilotinib is a weak inhibitor of CYP3A4 but since CYP3A4 mediated metabolism is only a minor pathway, a clinically relevant interaction is unlikely.

Coadministration has not been studied. Diltiazem is metabolised by CYP3A4 and CYP2D6. Nilotinib is a potent inhibitor of CYP3A4 in vitro but only a weak inhibitor in vivo; it is a moderate inhibitor of CYP2D6 in vitro but the in vivo effect has yet to be determined. However, clinically relevant CYP2D6 mediated interactions are unlikely. Diltiazem is a moderate inhibitor of CYP3A4, potentially increasing nilotinib exposure. Concurrent use of CYP3A4 inhibitors should be avoided as nilotinib is relatively toxic. If coadministration is unavoidable, a decrease of the nilotinib dose to 50% of the original dose should be considered. However, there are no clinical data with this dose adjustment in patients receiving CYP3A4 inhibitors. Monitoring of nilotinib plasma concentrations should be considered, if available. 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. Diphenhydramine is mainly metabolised by CYP2D6. Nilotinib is a moderate inhibitor of CYP2D6 in vitro but the in vivo effect has yet to be determined. However, a clinically relevant interaction is unlikely. Use nilotinib with caution when is coadministered with a drug with a known risk of Torsade de Pointes. In patients, therapeutic doses of nilotinib have been shown to prolong the QTc interval. If coadministration is necessary, close monitoring including ECG assessment is recommended. 

Coadministration has not been studied. Dipyridamole is glucuronidated by many UGTs, specifically those of the UGT1A subfamily. Nilotinib is an inhibitor of UGT1A1 in vitro and may increase concentrations of dipyridamole. 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 pharmacokinetic interaction is unlikely. Disopyramide is metabolised by CYP3A4 (25%) and 50% of the drug is eliminated unchanged in the urine. Nilotinib is a weak inhibitor of CYP3A4 but since CYP3A4 mediated metabolism is only a minor pathway, a clinically relevant interaction is unlikely. However, use nilotinib with caution when coadministering with a drug with a known risk of Torsade de Pointes. In patients, therapeutic doses of nilotinib have been shown to prolong the QTc interval with approximately 20 msec. 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 metabolised by CYP2D6 (10-20%) and CYP3A4 (<1%). Nilotinib is a potent inhibitor of CYP3A4 in vitro but only a weak inhibitor in vivo; it is a moderate inhibitor of CYP2D6 in vitro but the in vivo effect has yet to be determined. However, since CYP-medicated metabolism is only a minor pathway, a clinically relevant interaction is unlikely. Note: Dolasetron may prolong the QT interval and nilotinib has been shown to prolong the QT interval in vitro. 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. Domperidone is mainly metabolised by CYP3A4. Nilotinib is a weak inhibitor of CYP3A4 and may increase concentrations of domperidone. The clinical relevance of this interaction is unknown. Nilotinib should be used with caution when co-administered with a drug with a known risk of Torsade de Pointes. Both domperidone and nilotinib 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. 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 nilotinib, or to be affected if co-administered with nilotinib.

Coadministration has not been studied. Doxazosin is metabolised mainly by CYP3A4. Nilotinib is a weak inhibitor of CYP3A4 and may increase concentrations of doxazosin. As the clinical relevance of this interaction is unknown, monitoring of blood pressure may be required. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Doxepin is metabolised to nordoxepin (a metabolite with comparable pharmacological activity as the parent compound) mainly by CYP2C19. In addition, doxepin and nordoxepin are metabolised by CYP2D6. Nilotinib is a moderate inhibitor of CYP2C19 in vitro but the in vivo effect has yet to be determined. However, clinically relevant CYP2C19 mediated interactions are unlikely.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Doxycycline is excreted in the urine and faeces as unchanged active substance. Between 40-60% of an administered dose can be accounted for in urine. Nilotinib does not interact with this metabolic pathway. 

Coadministration has not been studied. Dronabinol is mainly metabolised by CYP2C9 and to a lesser extent by CYP3A4. Nilotinib is a potent inhibitor of CYP3A4 but only a weak inhibitor in vivo; it also potently inhibits CYP2C9 but the in vivo effect has yet to be determined. However, exposure of dronabinol may be increased. 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. Drospirenone is metabolised to a minor extent via CYP3A4. Nilotinib is a weak inhibitor of CYP3A4, however since CYP3A4 mediated metabolism is only a minor pathway, a clinically relevant interaction is unlikely.

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. Nilotinib is absorbed within 3 h. However, 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 metabolised by CYP2D6 and CYP1A2. Nilotinib is a moderate inhibitor of CYP2D6 in vitro but the in vivo effect has yet to be determined. However, clinically relevant CYP2CD6 mediated interactions are unlikely. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dutasteride is mainly metabolised by CYP3A4. Nilotinib is a weak inhibitor of CYP3A4 and may increase concentrations of dutasteride. However, since dutasteride has a wide therapeutic index, a clinically relevant interaction is unlikely.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dydrogesterone is metabolised to dihydrodydrogesterone (possibly via CYP3A4). Nilotinib is a weak inhibitor of CYP3A4, however since CYP3A4 mediated metabolism is only a minor pathway, a clinically relevant interaction is unlikely.

Coadministration has not been studied. Edoxaban is transported via P-gp. Concentrations may be increased by inhibition of P-gp by nilotinib. As the clinical relevance of this interaction is unknown, monitoring may be required.

Coadministration has not been studied. Eltrombopag is metabolised by cleavage conjugation (via UGT1A1, UGT1A3) and oxidation (via CYP1A2 and CYP2C8). Nilotinib is an inhibitor of CYP2C8 and an inhibitor of UGT1A1 in vitro, and may increase concentrations of eltrombopag. As the clinical relevance of these interactions is unknown, monitoring may be required.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Enalapril is hydrolysed to enalaprilat which is renally eliminated (possibly via OATs). 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Enoxaparin does not undergo cytochrome metabolism but is desulphated and depolymerised in the liver, and is predominantly renally excreted. Nilotinib 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 metabolism and clearance a clinically significant interaction is unlikely. Ertapenem is mainly eliminated through the kidneys by glomerular filtration with tubular secretion playing a minor role. Nilotinib does not interact with this metabolic pathway.

Coadministration has not been studied and is not recommended. Erythromycin may increase nilotinib concentrations due to inhibition of CYP3A4. Concurrent use of potent CYP3A4 inhibitors should be avoided as nilotinib is relatively toxic and can cause dose-related QT-prolongation. If coadministration is clinically necessary, the product labels for nilotinib recommend a dose reduction of 50%. However, there are no clinical data with this dose adjustment in patients receiving CYP3A4 inhibitors. Monitoring of nilotinib plasma concentrations should be considered, if available. If coadministration is necessary, close monitoring including ECG assessment is recommended.

Coadministration has not been studied. Escitalopram is metabolised by CYPs 2C19 (37%), 2D6 (28%) and 3A4 (35%) to form N-desmethylescitalopram. Nilotinib is a potent inhibitor of CYP3A4 in vitro but only a weak inhibitor in vivo; it is a moderate inhibitor of CYP2C19 and CYP2D6 in vitro but the in vivo effect has yet to be determined. Although clinically relevant CYP2C19 and CYP2D6 mediated interactions are unlikely, monitoring may be required. Furthermore, use nilotinib with caution when coadministered with a drug with a known risk of Torsade de Pointes. In patients, therapeutic doses of nilotinib have been shown to prolong the QTc interval. If coadministration is necessary, close monitoring including ECG assessment is recommended.

The solubility of nilotinib is pH dependent. In healthy volunteers (n=22), nilotinib (single dose of 400 mg) coadministered with esomeprazole (40 mg once daily for 5 days) decreased nilotinib AUC and Cmax by 34% and 27%, respectively. Furthermore, in patients with Ph+ CML-CP, the use of proton pump inhibitors or H2 antagonists did not seem to affect the efficacy of nilotinib in patients. Monitoring of nilotinib plasma concentrations should still be considered, if available.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Estazolam is metabolised to its major metabolite 4-hydroxyestazolam via CYP3A4. Nilotinib is a weak inhibitor of CYP3A4 and may increase concentrations of estazolam. However, since estazolam does not have a narrow therapeutic index, a clinically relevant interaction is unlikely.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Estradiol is metabolised by CYP3A4, CYP1A2 and is glucuronidated. Nilotinib is a weak inhibitor of CYP3A4, however since CYP3A4 mediated metabolism is only a minor pathway, a clinically relevant interaction is unlikely.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ethambutol is partly metabolised by alcohol dehydrogenase (20%) and partly eliminated unchanged in the faeces (20%) and urine (50%). Nilotinib 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). Nilotinib is a weak inhibitor of CYP3A4 and UGT1A1, and may increase concentrations of ethinylestradiol. However, a clinically relevant interaction is unlikely. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ethionamide is extensively metabolised in the liver with animal studies suggesting involvement of flavin-containing monooxygenases. Nilotinib does not interact with this metabolic pathway. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Etonogestrel is metabolised by CYP3A4. Nilotinib is a weak inhibitor of CYP3A4 and may increase concentrations of etongestrel. However, since etonogestrel does not have a narrow therapeutic index, a clinically relevant interaction is unlikely.

Coadministration has not been studied. Everolimus is mainly metabolised by CYP3A4 and is a substrate of P-gp. Nilotinib is a potent inhibitor of CYP3A4 in vitro but only a weak inhibitor in vivo; it is also an inhibitor of P-gp in vitro but the in vivo effect has yet to be determined. Therefore, concentrations of everolimus may potentially increase. Furthermore, due to the risk of additive haematological toxicity, haematological parameters should also 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. Nilotinib is absorbed in within 3 h. However, 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. Nilotinib is an inhibitor of UGT1A1 in vitro and may increase concentrations of ezetimibe. However, since ezetimibe has a wide therapeutic index, a clinically relevant interaction is unlikely.

The solubility of nilotinib is pH dependent. In healthy volunteers (n=52), nilotinib (single dose of 400 mg) administered 10 hours after and 2 hours before famotidine (multiple doses of 20 mg) showed no significant change in nilotinib pharmacokinetics famotidine. Therefore, when the concurrent use of a H2 blocker is necessary, it may be administered approximately 10 hours before and approximately 2 hours after the dose of nilotinib. Although, use of proton pump inhibitors or H2 antagonists did not seem to affect the efficacy of nilotinib in patients with Ph+ CML-CP, monitoring of nilotinib plasma concentrations should be considered, if available.

Coadministration has not been studied. Felodipine is metabolised by CYP3A4. Nilotinib is a weak inhibitor of CYP3A4 and may increase concentrations of felodipine. As the clinical relevance of this interaction is unknown, monitoring of blood pressure is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fenofibrate is hydrolysed to an active metabolite, fenofibric acid. Nilotinib does not interact with this pathway.

Coadministration has not been studied. Fentanyl undergoes extensive CYP3A4 metabolism. Nilotinib is a weak inhibitor of CYP3A4 and may increase the concentrations of fentanyl. As the clinical relevance of this interaction is unknown, close monitoring for toxicity is recommended. 

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. Nilotinib is a weak inhibitor of CYP3A4 and may increase concentrations of finasteride. However, since finasteride has a wide therapeutic index, a clinically relevant interaction is unlikely.

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 metabolised mainly via CYP2D6, with a proportion (approximately 30%) of the parent drug also renally eliminated as unchanged drug. Nilotinib is a moderate inhibitor of CYP2D6 in vitro but the in vivo effect has yet to be determined. Therefore the clinical relevance of this interaction is unknown. Use nilotinib with caution when coadministering with a drug with a known risk of Torsade de Pointes. In patients, therapeutic doses of nilotinib have been shown to prolong the QTc interval with approximately 20 msec. If coadministration is necessary, close monitoring including ECG assessment is recommended.

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

Coadministration has not been studied and is not recommended as nilotinib concentrations may increase due to inhibition of CYP3A4 by fluconazole. Concurrent use of CYP3A4 inhibitors should be avoided as nilotinib is relatively toxic. If coadministration is unavoidable, a decrease of the nilotinib dose to 50% of the original dose should be considered. However, there are no clinical data with this dose adjustment in patients receiving CYP3A4 inhibitors. Note: Use nilotinib with caution when coadministered with a drug with a known risk of Torsade de Pointes. In patients, therapeutic doses of nilotinib have been shown to prolong the QTc interval with approximately 20 msec. Coadministration is not recommended. If coadministration is necessary, close monitoring including ECG assessment is recommended. Monitoring of nilotinib plasma concentrations should be considered, if available. 

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. Nilotinib 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. Nilotinib 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 metabolised in the liver to inactive metabolites, possibly via CYP3A. Nilotinib is a weak inhibitor of CYP3A4 and may increase concentrations of fludrocortisone. However, since fludrocortisone has a wide therapeutic index, a clinically relevant interaction is unlikely.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Flunitrazepam is metabolised mainly via CYP3A4 and CYP2C19. Nilotinib is a potent inhibitor of CYP3A4 in vitro but only a weak inhibitor in vivo; it is a moderate inhibitor of CYP2C19 in vitro but the in vivo effect has yet to be determined. However, since flunitrazepam does not have a narrow therapeutic index, a clinically relevant interaction is unlikely.

Coadministration has not been studied. Fluoxetine is metabolised by CYP2D6 and CYP2C9 and to a lesser extent by CYP2C19 and CYP3A4 to form norfluoxetine. Nilotinib is a potent inhibitor of CYP3A4 and CYP2C9 in vitro but only a weak inhibitor in vivo; it is a moderate inhibitor of CYP2C19 and CYP2D6 in vitro but the in vivo effect has yet to be determined. Although clinically relevant interactions mediated by CYPs 2C19 and 2D6 are unlikely, monitoring may be required. 

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Fluphenazine is metabolised by CYP2D6. Nilotinib is a moderate inhibitor of CYP2D6 in vitro but the in vivo effect has yet to be determined. However, clinically relevant CYP2D6 mediated interactions are unlikely. Use nilotinib with caution when coadministered with a drug with a known risk of Torsade de Pointes. In patients, therapeutic doses of nilotinib 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 also be monitored if coadministered. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nilotinib is a potent inhibitor of CYP3A4 in vitro but only a weak inhibitor in vivo; it also potently inhibits CYP2C9 and CYP2C8 in vitro but the in vivo effect has yet to be determined. Furthermore, nilotinib is a moderate inhibitor of CYP2C19 and CYP2D6 in vitro but again, the in vivo effect has yet to be determined. However, since flurazepam does not have a narrow therapeutic index, clinically relevant interactions are unlikely.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fluticasone is metabolised by CYP3A4. Nilotinib is a weak inhibitor of CYP3A4 and may increase concentrations of fluticasone. However, since fluticasone has a wide therapeutic index, a clinically relevant interaction is unlikely.

Coadministration has not been studied. Fluvastatin is mainly metabolised by CYP2C9. Nilotinib is a potent inhibitor of CYP2C9 in vitro but the in vivo effect has yet to be determined. This may potentially cause an increase in fluvastatin exposure. As the clinical relevance of these interactions is unknown, monitoring for toxicity may be required. 

Coadministration has not been studied. Fluvoxamine is metabolised mainly by CYP2D6 and to a lesser extent by CYP1A2. Nilotinib is a moderate inhibitor of CYP2D6 in vitro but the in vivo effect has yet to be determined. Although clinically relevant CYP2D6 mediated interactions are unlikely, monitoring may be required. Furthermore, fluvoxamine inhibits CYPs 1A2, 2C19, 3A4, 2C9, and so nilotinib concentrations may be slightly increased when coadministered with fluvoxamine. 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. Fondaparinux does not undergo cytochrome metabolism but is predominantly renally eliminated. Nilotinib 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 as another pathway. As multiple CYP450 and UGT enzymes catalyse the transformation, the potential for a clinically relevant pharmacokinetic interaction is low.

Coadministration has not been studied but should be approached with caution. Fosaprepitant is rapidly, almost completely, converted to the active metabolite aprepitant. Nilotinib does not interact with this metabolic pathway. Aprepitant is mainly metabolised by CYP3A4 and to a lesser extent by CYP1A2 and CYP2C19. Nilotinib is an inhibitor of CYP3A4 and CYP2C9 (in vitro), and may increase concentrations of aprepitant. Furthermore, during treatment aprepitant is a moderate inhibitor of CYP3A4 and may increase concentrations of nilotinib during the three days of coadministration. Therefore, coadministration is not recommended. If coadministration is unavoidable, reduce the nilotinib dose to 50% of the original dose during the few days of coadministration. Monitor closely for nilotinib toxicity. After treatment, aprepitant is a weak inducer of CYP3A4, CYP2C9 and UGT. Concentrations of nilotinib 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. Nilotinib is an inhibitor of CYP2C9 and CYP2C19 in vitro and may increase concentrations of phenytoin. Monitoring for phenytoin toxicity may be necessary. Monitor phenytoin plasma concentrations, if available. Furthermore, phenytoin is a potent inducer of CYP3A4, UGT and P-gp. Concentrations of nilotinib may decrease due to CYP3A4 induction. In healthy volunteers (n=15), coadministration of nilotinib (400 mg single oral dose) and the strong CYP3A4 inducer, rifampicin (600 mg once daily for 12 days), decreased nilotinib AUC and Cmax by 80% and 64%, respectively. A similar effect may occur with fosphenytoin. Therefore, coadministration should be avoided. If coadministration is unavoidable, the dose of nilotinib may need to be increased depending on patient tolerability. No absolute dose adjustment advice can be given, due to the non-linear pharmacokinetics. A dosing regimen more frequent than twice daily may be necessary to obtain adequate nilotinib exposure. Consider monitoring of nilotinib 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). Nilotinib is an inhibitor of UGT1A1 in vitro. However, since glucuronidation via UGT1A1 is only a minor pathway, a clinically relevant interaction is unlikely.

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. Nilotinib does not interact with this pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Gemfibrozil is metabolised by UGT2B7. Nilotinib 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. Nilotinib 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 metabolised by CYP3A4 and to a lesser extent by CYP2C9 and CYP2C19. Nilotinib is a potent inhibitor of CYP3A4 in vitro but only a weak inhibitor in vivo; it also potently inhibits CYP2C9 in vitro but the in vivo effect has yet to be determined. Furthermore, nilotinib is a moderate inhibitor of CYP2C19 in vitro but again, the in vivo effect has yet to be determined. Since gestodene does not have a narrow therapeutic index, a clinically relevant interaction is unlikely.

Coadministration has not been studied. Glibenclamide is mainly metabolised by CYP3A4 and to a lesser extent by CYP2C9. Nilotinib is a potent inhibitor of CYP3A4 and CYP2C9 in vitro but only a weak inhibitor in vivo. Therefore, concentrations of glibenclamide may increase. As the clinically relevance of this interaction is unknown, monitoring may be required.

Coadministration has not been studied. Gliclazide is metabolised mainly by CYP2C9 and to a lesser extent by CYP2C19. Nilotinib is a potent inhibitor of CYP2C9 in vitro but the in vivo effect has yet to be determined; it is also a moderate inhibitor of CYP2C19 in vitro but again, the in vivo effect has yet to be determined. Therefore, concentrations of gliclazide may increase. As the clinically relevance of these interactions is unknown, monitoring may be required.

Coadministration has not been studied. Glimepiride is mainly metabolised by CYP2C9. Nilotinib is a potent inhibitor of CYP2C9 in vitro but the in vivo effect has yet to be determined. Concentrations of glimepiride may increase. As the clinical relevance of this interaction is unknown, monitoring may be required.

Coadministration has not been studied. Glipizide is mainly metabolised by CYP2C9. Nilotinib is a potent inhibitor of CYP2C9 in vitro but the in vivo effect has yet to be determined. Concentrations of glipizide may increase. As the clinical relevance of this interaction is unknown, monitoring may be required.

Coadministration has not been studied. Granisetron is metabolised by CYP3A4 and is a substrate of P-gp. Nilotinib is a weak inhibitor of CYP3A4 and inhibits P-gp in vitro, potentially increasing concentrations of granisetron. However, the clinical relevance of this interaction is unknown. Note: Granisetron may prolong the QT interval and nilotinib 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, close monitoring including ECG assessment is recommended.

Grapefruit juice is a known inhibitor of CYP3A4, potentially increasing nilotinib concentrations. In healthy volunteers (n=21), nilotinib (single dose of 400 mg) coadministered with grapefruit juice (240 mL double strength, single dose) increased nilotinib Cmax and AUC by 60% and 29%, respectively. However, the magnitude of this potential interaction is concentration-, dose- and preparation-dependent and varies widely across different brands of grapefruit juice. The product label for nilotinib advises to avoid coadministration with grapefruit juice.

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

Coadministration has not been studied. Less than 1% of a griseofulvin dose is excreted unchanged via the kidneys. Nilotinib does not interfere with griseofulvin elimination pathway. However, griseofulvin is a liver microsomal enzyme inducer and may lower plasma levels, reducing the efficacy of concomitantly administered medicinal products metabolised by CYP3A4, such as nilotinib. Close monitoring is recommended.

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>UGT1A4 and UGT1A9), carbonyl reduction as well as oxidative metabolism (CYP3A4 and CYP2D6). Nilotinib is a potent inhibitor of CYP3A4 but only a weak inhibitor in vivo; it is a moderate inhibitor of CYP2D6 in vitro but the in vivo effect has yet to be determined. However, clinically relevant CYP2D6 mediated interactions are unlikely. Use nilotinib with caution when coadministered with a drug with a known risk of Torsade de Pointes. In patients, therapeutic doses of nilotinib 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. Nilotinib 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 nilotinib. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Hydrochlorothiazide is not metabolised and is cleared by the kidneys via OAT1. Significant interactions are not expected with nilotinib.

Coadministration has not been studied. Hydrocodone is metabolised by CYP2D6 to hydromorphone and by CYP3A4 to norhydrocodone, both of which have analgesic effects. Nilotinib is a potent inhibitor of CYP3A4 in vitro but only a weak inhibitor in vivo; it is a moderate inhibitor of CYP2D6 in vitro but the in vivo effect has yet to be determined. Although clinically relevant CYP2D6 mediated interactions are unlikely, monitoring for toxicity may be required.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Hydrocortisone is metabolised by CYP3A4. Nilotinib is a weak inhibitor of CYP3A4 and may increase concentrations of hydrocortisone. However, since hydrocortisone has a wide therapeutic index, a clinically relevant interaction is unlikely.

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. Nilotinib does 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. 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 pharmacokinetic interaction is unlikely. Hydroxyzine is partly metabolised by alcohol dehydrogenase and partly by CYP3A4. Nilotinib is a weak inhibitor of CYP3A4, but since hydroxyzine does not have a narrow therapeutic index, a clinically relevant interaction is unlikely. However, use nilotinib with caution when coadministered with a drug with a known risk of Torsade de Pointes. In patients, therapeutic doses of nilotinib 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. 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. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ibuprofen is metabolised mainly by CYP2C9 and to a lesser extent by CYP2C8 and direct glucuronidation. Nilotinib is a weak inhibitor of CYP2C8 and an inhibitor of CYP2C9 in vitro. However, since ibuprofen does not have a narrow therapeutic index, a clinically relevant interaction is unlikely. 

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Iloperidone is metabolised by CYP3A4 and CYP2D6. Nilotinib is a potent inhibitor of CYP3A4 but only a weak inhibitor in vivo; it is a moderate inhibitor of CYP2D6 in vitro but the in vivo effect has yet to be determined. However, clinically relevant CYP2D6 mediated interactions are unlikely. Use nilotinib with caution when coadministered with a drug with a known risk of Torsade de Pointes. In patients, therapeutic doses of nilotinib 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 by active tubular secretion. Nilotinib does not interact with this metabolic pathway. 

Coadministration has not been studied. Imipramine is metabolised by CYPs 3A4, 2C19 and 1A2 to desipramine. Imipramine and desipramine are both metabolised by CYP2D6. Nilotinib is a potent inhibitor of CYP3A4 in vitro but only a weak inhibitor in vivo; it is a moderate inhibitor of CYP2C19 and CYP2D6 in vitro but the in vivo effect has yet to be determined. Although clinically relevant CYP2C19 and CYP2D6 mediated interactions are unlikely, monitoring may be required. Note, use nilotinib with caution when coadministered with a drug with a known risk of Torsade de Pointes. In patients, therapeutic doses of nilotinib 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 metabolised by CYP P450. Nilotinib is a potent inhibitor of CYP3A4 in vitro but only a weak inhibitor in vivo; it also potently inhibits CYP2C8 in vitro but the in vivo effect has yet to be determined. Furthermore, nilotinib is a moderate inhibitor of CYP2D6 in vitro but again, the in vivo effect has yet to be determined. Although clinically relevant CYP2D6 mediated interactions are unlikely, monitoring for toxicity of indapamide and monitoring of blood pressure may be required. Nilotinib has also 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. 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. Interleukin-2 is mainly eliminated by glomerular filtration. Nilotinib does not interact with this pathway.

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. Nilotinib does not interact with this metabolic pathway.

Coadministration has not been studied. Irbesartan is metabolised by glucuronidation and oxidation (mainly CYP2C9). Nilotinib is a potent inhibitor of CYP2C9 and may increase irbesartan exposure. Monitoring of blood pressure may be required.

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. Nilotinib does not interact with this metabolic pathway. 

Coadministration has not been studied. In vitro studies suggest that CYP3A4 has a role in nitric oxide formation from isosorbide dinitrate. Nilotinib is a weak inhibitor of CYP3A4 and may increase concentrations of isosorbide dinitrate. The clinical relevance of this interaction is unknown and monitoring may be required.

Coadministration has not been studied and is not recommended as nilotinib concentrations may increase due to inhibition of CYP3A4 by itraconazole. Concurrent use of CYP3A4 inhibitors should be avoided as nilotinib is relatively toxic. If combination is unavoidable, decrease of the nilotinib dose to 50% of the original dose should be considered. However, there are no clinical data with this dose adjustment in patients receiving CYP3A4 inhibitors. Note: Use nilotinib with caution when coadministered with a drug with a known risk of Torsade de Pointes. In patients, therapeutic doses of nilotinib have been shown to prolong the QTc interval with approximately 20 msec. Coadministration is not recommended. If coadministration is necessary, close monitoring including ECG assessment is recommended. Monitoring of nilotinib plasma concentrations should be considered, if available.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Ivabradine is metabolised by CYP3A4. Nilotinib is a weak inhibitor of CYP3A4 and may increase concentrations of ivabradine. The clinical relevance of this interaction is unknown. However, nilotinib has been shown to prolong the QTc interval and according to the product labels the use of ivabradine in patients treated with QT prolonging medicinal products should be avoided. If the coadministration is 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 is not recommended. In healthy volunteers (n=26), coadministration of nilotinib (single dose of 200 mg) and ketoconazole (400 mg daily for 6 days) increased nilotinib Cmax and AUC by 1.8- and 3-fold, respectively, due to CYP3A4 inhibition. Concurrent use of CYP3A4 inhibitors should be avoided as nilotinib is relatively toxic. If coadministration is unavoidable, decrease of the nilotinib dose to 50% of the original dose should be considered. However, there are no clinical data with this dose adjustment in patients receiving CYP3A4 inhibitors. Note: Use nilotinib with caution when coadministered with a drug with a known risk of Torsade de Pointes. In patients, therapeutic doses of nilotinib have been shown to prolong the QTc interval with approximately 20 msec. Coadministration is not recommended. If coadministration is necessary, close monitoring including ECG assessment is recommended. Monitoring of nilotinib plasma concentrations should be considered, if available.

Coadministration has not been studied. Labetalol is mainly glucuronidated (via UGT1A1 and UGT2B7). Nilotinib is an inhibitor of UGT1A1 in vitro and may increase concentrations of labetalol. As the clinical relevance of this interaction is unknown, monitoring of blood pressure may be required.

Coadministration has not been studied. Lacidipine is metabolised by CYP3A4. Nilotinib is a weak inhibitor of CYP3A4 and may increase concentrations of lacidipine. As the clinical relevance of this interaction is unknown, monitoring of blood pressure may be required.

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. The solubility of nilotinib is pH dependent. There was a modest reduction in the rate and extent of nilotinib absorption when coadministered with esomeprazole at the 40-mg once-daily dose (AUC decreased by 34%, Cmax decreased by 27%). Although, use of proton pump inhibitors or H2 antagonists did not seem to affect the efficacy of nilotinib in patients with Ph+ CML-CP, monitoring of nilotinib plasma concentrations should be considered, if available.

Coadministration has not been studied. Lercanidipine is mainly metabolised by CYP3A4. Nilotinib is a weak inhibitor of CYP3A4 and may increase concentrations of lercanidipine. As the clinical relevance of this interaction is unknown, monitoring of blood pressure may be required.

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). Nilotinib does not interact with this metabolic pathway. However, nilotinib should be used with caution when co-administered with a drug with a known risk of QTc interval prolongation. In patients, therapeutic doses of nilotinib have been shown to prolong the QTc interval by approximately 20 msec. 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 metabolised by CYP2D6. Nilotinib is a moderate inhibitor of CYP2D6 in vitro but the in vivo effect has yet to be determined. However, clinically relevant CYP2D6 mediated interactions are unlikely. Use nilotinib with caution when coadministered with a drug with a known risk of Torsade de Pointes. In patients, therapeutic doses of nilotinib 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 metabolised by CYP3A4 and is glucuronidated to a minor extent. Nilotinib is a weak inhibitor of CYP3A4 and may increase concentrations of levonorgestrel. However, since levonorgestrel does not have a narrow therapeutic index, a clinically relevant interaction is unlikely.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Levonorgestrel is metabolised by CYP3A4 and is glucuronidated to a minor extent. Nilotinib is a weak inhibitor of CYP3A4 and may increase concentrations of levonorgestrel. However, since levonorgestrel does not have a narrow therapeutic index, a clinically relevant interaction is unlikely.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Levothyroxine is metabolised by deiodination (by enzymes of deiodinase family) and glucuronidation. Nilotinib does not interact with levothyroxine metabolism. 

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. Nilotinib does not inhibit or induce CYP1A2.

Coadministration has not been studied. Linagliptin is mainly eliminated as parent compound in the faeces with metabolism by CYP3A4 representing a minor pathway. Nilotinib is a weak inhibitor of CYP3A4 and since CYP3A4 mediated metabolism is only a minor pathway, a clinically relevant interaction is unlikely. Linagliptin is a substrate of P-gp and an inhibitor of CYP3A4. Nilotinib concentrations may increase due to inhibition of CYP3A4 by linagliptin. 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. 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 by the kidneys. Lithium is freely filtered at a rate that is dependent upon the glomerular filtration rate, therefore no pharmacokinetic interaction is expected. However, use nilotinib with caution when coadministered with a drug with a known risk of Torsade de Pointes. In patients, therapeutic doses of nilotinib 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 metabolised by CYP3A4 and CYP2C8. Nilotinib is a potent inhibitor of CYP3A4 but only a weak inhibitor in vivo; it also potently inhibits CYP2C8 in vitro but the in vivo effect has yet to be determined. However, due to the wide therapeutic index of loperamide, this interaction 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 metabolised mainly by CYP3A4 and to a lesser extent by CYP2D6. Nilotinib is a potent inhibitor of CYP3A4 in vitro but only a weak inhibitor in vivo; it is a moderate inhibitor of CYP2D6 in vitro but the in vivo effect has yet to be determined. However, this interaction is unlikely to be clinically relevant since loratadine has a wide therapeutic index.

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 nilotinib. 

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

Coadministration has not been studied. Losartan is converted to its active metabolite mainly by CYP2C9 in the range of clinical concentrations. Nilotinib is a potent inhibitor of CYP2C9 in vitro but the in vivo effect has yet to be determined. Concentrations of losartan may increase and monitoring of blood pressure may be required.

Coadministration has not been studied. Lovastatin is metabolised by CYP3A4. Nilotinib is a weak inhibitor of CYP3A4 and may increase concentrations of lovastatin. As the clinical relevance of this interaction is unknown, monitoring may be required.

Coadministration has not been studied. Macitentan is metabolised mainly by CYP3A4 and to a lesser extent by CYPs 2C19, 2C9 and 2C8. Nilotinib is a potent inhibitor of CYP3A4 in vitro but only a weak inhibitor in vivo; it also potently inhibits CYP2C8 and CYP2C9 in vitro but the in vivo effect has yet to be determined. Furthermore, nilotinib is a moderate inhibitor of CYP2C19 in vitro but again, the in vivo effect has yet to be determined. However, exposure to macitentan may increase and as the clinical relevance of these interactions is unknown, monitoring for toxicity may be required. 

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 metabolised by CYP2D6. Nilotinib is a moderate inhibitor of CYP2D6 in vitro but the in vivo effect has yet to be determined. However, clinically relevant CYP2D6 mediated interactions are unlikely.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Medroxyprogesterone is metabolised by CYP3A4. Nilotinib is a weak inhibitor of CYP3A4 and may increase concentrations of medroxyprogesterone. However, since medroxyprogesterone does not have a narrow therapeutic index, a clinically relevant interaction is unlikely.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Medroxyprogesterone is metabolised by CYP3A4. Nilotinib is a weak inhibitor of CYP3A4 and may increase concentrations of medroxyprogesterone. However, since medroxyprogesterone does not have a narrow therapeutic index, a clinically relevant interaction is unlikely.

Coadministration has not been studied. Mefenamic acid is metabolised by CYP2C9 and glucuronidated by UGT2B7 and UGT1A9. Nilotinib is an inhibitor of CYP2C9 in vitro and may increase concentrations of mefenamic acid. 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. Megestrol acetate is mainly eliminated in 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 with in vitro data suggesting it is a substrate of the renal transporters OAT3>OAT1. Nilotinib does not interact with this elimination pathway. 

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

Coadministration has not been studied and should be approached with caution. Metamizole may decrease nilotinib concentrations due to induction of CYP3A4. A decrease in nilotinib exposure can lead to decreased efficacy. Selection of an alternative concomitant medication with no or minimal enzyme or transporter induction potential is recommended. As the clinical relevance of this interaction is unknown, close 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). Nilotinib does not interact with metformin metabolic and elimination pathway.

Coadministration has not been studied. Methadone is demethylated by CYP3A4. Nilotinib is a weak inhibitor of CYP3A4 and so concentrations of methadone may increase. Furthermore, nilotinib should be used with caution when coadministered with a drug with a known risk of Torsade de Pointes. In patients, therapeutic doses of nilotinib have been shown to prolong the QTc interval by approximately 20 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. 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 nilotinib, or to be altered by coadministration with nilotinib.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Methylphenidate is not metabolised 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 metabolised by CYP3A4. Nilotinib is a weak inhibitor of CYP3A4 and may increase concentrations of methylprednisolone. However, since methylprednisolone has a wide therapeutic index, a clinically relevant interaction is unlikely.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metoclopramide is partially metabolised by the CYP450 system (mainly CYP2D6). Nilotinib is a moderate inhibitor of CYP2D6 in vitro but the in vivo effect has yet to be determined. However, since CYP-mediated metabolism is only a minor pathway, a clinically relevant interaction is unlikely.

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 metabolised by CYP2D6. Nilotinib is a moderate inhibitor of CYP2D6 in vitro but the in vivo effect has yet to be determined. However, clinically relevant CYP2D6 mediated interactions are unlikely.

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 nilotinib 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 metabolised mainly by CYP2D6 and to a lesser extent CYP1A2. Nilotinib is a moderate inhibitor of CYP2D6 in vitro but the in vivo effect has yet to be determined. However, clinically relevant CYP2D6 mediated interactions are unlikely.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Mianserin is metabolised by CYPs 2D6 and 1A2, and to a lesser extent by CYP3A4. Nilotinib is a potent inhibitor of CYP3A4 in vitro but only a weak inhibitor in vivo; it is a moderate inhibitor of CYP2D6 in vitro but the in vivo effect has yet to be determined. However, clinically relevant CYP2D6 mediated interactions are unlikely.

Coadministration has not been studied. Miconazole inhibits CYP2C9 and CYP3A4, potentially increasing nilotinib concentrations. Oromucosal coadministration may increase nilotinib concentrations due to inhibition of CYP3A4. Concurrent use of CYP3A4 inhibitors should be avoided as nilotinib is relatively toxic. If coadministration is unavoidable, a decrease of the nilotinib dose to 50% of the original dose should be considered. However, there are no clinical data with this dose adjustment in patients receiving CYP3A4 inhibitors. Note: Use nilotinib with caution when coadministered with a drug with a known risk of Torsade de Pointes. In patients, therapeutic doses of nilotinib have been shown to prolong the QTc interval with approximately 20 msec. Coadministration is not recommended. If coadministration is necessary, close monitoring including ECG assessment is recommended. Monitoring of nilotinib plasma concentrations should be considered, if available. Dermal application: No a priori dosage adjustment is recommended for nilotinib with dermal administration of miconazole, since systemic exposure of miconazole is limited when used topically.

Midazolam is metabolised by CYP3A4. Nilotinib is a weak inhibitor of CYP3A4. In a study with patients with CML (n=19), coadministration of nilotinib (400 mg twice daily for 12 days) and midazolam (2 mg single dose, oral) increased midazolam AUC and Cmax by 2- and 2.6-fold, respectively. Since midazolam does not have a narrow therapeutic index, a clinically relevant interaction is unlikely. Monitoring for toxicity is recommended.

Midazolam is metabolised by CYP3A4. Nilotinib is a weak inhibitor of CYP3A4. In a study with patients with CML (n=19), coadministration of nilotinib (400 mg twice daily for 12 days) and midazolam (2 mg single dose, oral) increased midazolam AUC and Cmax by 2- and 2.6-fold, respectively. Monitoring for toxicity is recommended.

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%). Nilotinib is unlikely to interfere with these pathways.

Coadministration has not been studied. Mirtazapine is metabolised to 8-hydroxymirtazapine by CYP2D6 and CYP1A2, and to N-desmethylmirtazapine mainly by CYP3A4. Nilotinib is a potent inhibitor of CYP3A4 in vitro but only a weak inhibitor in vivo; it is a moderate inhibitor of CYP2D6 in vitro but the in vivo effect has yet to be determined. Although a clinically relevant CYP2D6 mediated interaction is unlikely, monitoring may be required.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Mometasone is metabolised by CYP3A4. Nilotinib is a weak inhibitor of CYP3A4 and may increase concentrations of mometasone. However, since mometasone has a wide therapeutic index, a clinically relevant interaction is unlikely.

Coadministration has not been studied. Montelukast is mainly metabolised by CYP2C8 and to a lesser extent by CYPs 3A4 and 2C9. Nilotinib is a potent inhibitor of CYP3A4 in vitro but only a weak inhibitor in vivo; it also potently inhibits CYP2C8 and CYP2C9 in vitro but the in vivo effect has yet to be determined. Although the clinical relevance of this interaction is unknown, monitoring for toxicity may be required.

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). Nilotinib is an inhibitor of UGT1A1 in vitro, however since UGT1A1 mediated metabolism is only a minor pathway, a clinically relevant interaction is unlikely.

Coadministration has not been studied and should be avoided. Moxifloxacin is predominantly glucuronidated by UGT1A1. Nilotinib is an inhibitor of UGT1A1 in vitro and may increase concentrations of moxifloxacin. The clinical relevance of this interaction is unknown. Nilotinib should be used with caution when co-administered with a drug with a known risk of Torsade de Pointes. In patients therapeutic doses of nilotinib have been shown to prolong the QTc interval by approximately 20 msec. 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. Mycophenolate is mainly glucuronidated by UGT1A9 and UGT2B7. Nilotinib does not inhibit or induce UGT1A9 or UGT2B7. 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. Nilotinib 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 metabolised in the liver by alpha-reductase. Nilotinib does not interact with this metabolic 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. Nilotinib is an inhibitor of CYP2C9 in vitro but since naproxen has a wide therapeutic index, this interaction is unlikely to be clinically relevant.

Coadministration has not been studied. Nateglinide is mainly metabolised by CYP2C9 (70%) and to a lesser extent CYP3A4 (30%). Nilotinib is a potent inhibitor of CYP3A4 in vitro but only a weak inhibitor in vivo. Furthermore, nilotinib is also a potent inhibitor of CYP2C9 in vitro but the in vivo effect has yet to be determined. Concentrations of nateglinide may increase due to CYP3A4 inhibition. 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. Nebivolol metabolism involves CYP2D6. Nilotinib is a moderate inhibitor of CYP2D6 in vitro but the in vivo effect has yet to be determined. However, clinically relevant CYP2D6 mediated interactions are unlikely.

Coadministration has not been studied. Nefazodone is metabolised mainly by CYP3A4 and is also an inhibitor of CYP3A4. Nefazodone may increase nilotinib concentrations due to inhibition of CYP3A4. Concurrent use of CYP3A4 inhibitors should be avoided as nilotinib is relatively toxic. If coadministration is unavoidable, decrease of the nilotinib dose to 50% of the original dose should be considered. However, there are no clinical data with this dose adjustment in patients receiving CYP3A4 inhibitors. Monitoring of nilotinib plasma concentrations should be considered, if available. If coadministration is necessary, close monitoring is recommended.

Coadministration has not been studied. Nicardipine is metabolised mainly by CYP3A4 and to a lesser extent by CYP2D6 and CYP2C8. Nilotinib is a potent inhibitor of CYP3A4 but only a weak inhibitor in vivo; it also potently inhibits CYP2C8 in vitro but the in vivo effect has yet to be determined. Furthermore, nilotinib is a moderate inhibitor of CYP2D6 in vitro but again, the in vivo effect has yet to be determined. As the clinical relevance of these interactions is unknown, monitoring of blood pressure is recommended. Furthermore, nicardipine inhibits CYP3A4 and could potentially increase nilotinib concentrations. No a priori dosage adjustment is recommended for nilotinib. Close monitoring of nilotinib tolerability is also 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 metabolised by xanthine oxidase and aldehyde oxidase. Nilotinib 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 nilotinib exposure.

Coadministration has not been studied. Nifedipine is metabolised mainly by CYP3A4. Nilotinib is a weak inhibitor of CYP3A4 and may increase concentrations of nifedipine. As the clinical relevance of this interaction is unknown, monitoring of blood pressure is recommended.

Coadministration has not been studied. Nimesulide is extensively metabolised in the liver following multiple pathways including CYP2C9. Nilotinib is an inhibitor of CYP2C9 in vitro. Although the clinical relevance of this interaction is unknown, monitoring may be required. 

Coadministration has not been studied. Nisoldipine is metabolised by CYP3A4. Nilotinib is a weak inhibitor of CYP3A4 and may increase concentrations of nisoldipine. As the clinical relevance of this interaction is unknown, monitoring of blood pressure may be required.

Coadministration has not been studied. Nitrendipine is extensively metabolised mainly by CYP3A4. Nilotinib is a weak inhibitor of CYP3A4 and may increase concentrations of nitrendipine. As the clinical relevance of this interaction is unknown, monitoring of blood pressure may be required.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nitrofurantoin is partly metabolised in the liver via glucuronidation and N-acetylation and partly eliminated in the urine as unchanged drug (30-40%). Nilotinib 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 metabolised to norgestrel (possibly by CYP3A4). Nilotinib is a weak inhibitor of CYP3A4 and may increase concentrations of norelgestromin. However, since medroxyprogesterone does not have a narrow therapeutic index, a clinically relevant interaction is unlikely.

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. Nilotinib 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 metabolised via CYP450. Nilotinib is a potent inhibitor of CYP3A4 in vitro but only a weak inhibitor in vivo; it also potently inhibits CYP2C8 and CYP2C9 in vitro but the in vivo effect has yet to be determined. Furthermore, nilotinib is a moderate inhibitor of CYP2D6 and CYP2C19 in vitro but again, the in vivo effect has yet to be determined. Since norgestimate does not have a narrow therapeutic index, a clinically relevant interaction is unlikely.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Norgestrel is a racemic mixture with levonorgestrel being biologically active. Levonorgestrel is mainly metabolised by CYP3A4. Nilotinib is a weak inhibitor of CYP3A4 and may increase concentrations of norgestrel. However, since levonorgestrel does not have a narrow therapeutic index, a clinically relevant interaction is unlikely.

Coadministration has not been studied. Nortriptyline is metabolised mainly by CYP2D6. Nilotinib is a moderate inhibitor of CYP2D6 in vitro but the in vivo effect has yet to be determined. Although clinically relevant CYP2D6 mediated interactions are unlikely, monitoring may be required. Furthermore, use nilotinib with caution when coadministered with a drug with a known risk of Torsade de Pointes. In patients, therapeutic doses of nilotinib 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 renally eliminated unchanged by glomerular filtration and active tubular secretion via both cationic and anionic transport systems. Nilotinib is unlikely to interact with this metabolic pathway. However, nilotinib should be used with caution when co-administered with a drug with a known risk of Torsade de Pointes. In patients therapeutic doses of nilotinib have been shown to prolong the QTc interval by approximately 20 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. Olanzapine is metabolised mainly by CYP1A2, but also by glucuronidation (UGT1A4). Nilotinib does not inhibit or induce CYP1A2 and UGT1A4. 

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. The solubility of nilotinib is pH dependent. There was a modest reduction in the rate and extent of nilotinib absorption when coadministered with esomeprazole at the 40-mg once-daily dose (AUC decreased by 34%, Cmax decreased by 27%). Although, use of proton pump inhibitors or H2 antagonists did not seem to affect the efficacy of nilotinib in patients with Ph+ CML-CP, monitoring of nilotinib plasma concentrations should be considered, if available.

Coadministration has not been studied. Ondansetron is metabolised mainly by CYP1A2 and CYP3A4 and to a lesser extent by CYP2D6. Ondansetron is a substrate of P-gp. Nilotinib is a potent inhibitor of CYP3A4 but only a weak inhibitor in vivo; it is a moderate inhibitor of CYP2D6 and P-gp in vitro but the in vivo effect has yet to be determined. Concentrations of ondansetron may increase but due to the wide therapeutic index of ondansetron, this interaction is unlikely to be clinically relevant. Note: Ondansetron may prolong the QT interval dose dependently and nilotinib 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. Nilotinib does not interact with this metabolic pathway. 

Coadministration has not been studied and should be avoided as significant decreases in nilotinib plasma exposure may occur due to induction of CYP3A4. Decreased nilotinib exposure can lead to decreased efficacy. Selection of an alternative concomitant medication with no or minimal enzyme or transporter induction potential is recommended. If coadministration is unavoidable, the dose of nilotinib might need to be increased depending on patient tolerability. No absolute dose adjustment advice can be given, due to the non-linear pharmacokinetics. A dosing regimen more frequent than twice daily may be necessary to obtain adequate nilotinib exposure. Consider monitoring of nilotinib plasma concentrations, if available.

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

Coadministration has not been studied. Oxycodone is metabolised principally to noroxycodone via CYP3A4 and oxymorphone via CYP2D6. Nilotinib is a potent inhibitor of CYP3A4 in vitro but only a weak inhibitor in vivo; it is a moderate inhibitor of CYP2D6 in vitro but the in vivo effect has yet to be determined. Although clinically relevant CYP2D6 mediated interactions are unlikely, monitoring for toxicity may be required.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Paliperidone is primarily renally eliminated (possibly via OCT) with minimal metabolism occurring via CYP2D6 and CYP3A4. Nilotinib is a potent inhibitor of CYP3A4 in vitro but only a weak inhibitor in vivo; it is a moderate inhibitor of CYP2D6 in vitro but the in vivo effect has yet to be determined. Since these are minor pathways, a clinically relevant interaction is unlikely.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction unlikely. Palonosetron is metabolised mainly by CYP3A4 and to a lesser extent by CYP2D6 and CYP1A2. Palonosetron is a substrate of P-gp. Nilotinib is a potent inhibitor of CYP3A4 but only a weak inhibitor in vivo; it is a moderate inhibitor of CYP2D6 and P-gp in vitro but the in vivo effect has yet to be determined. Concentrations of palonosetron may increase, but due to the wide therapeutic index of palonosetron, this interaction is unlikely to be clinically relevant.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as pamidronic acid is not metabolised and is cleared as unchanged drug via urine.

Coadministration has not been studied. The solubility of nilotinib is pH dependent. There was a modest reduction in the rate and extent of nilotinib absorption when coadministered with esomeprazole at the 40-mg once-daily dose (AUC decreased by 34%, Cmax decreased by 27%). Although, use of proton pump inhibitors or H2 antagonists did not seem to affect the efficacy of nilotinib in patients with Ph+ CML-CP, monitoring of nilotinib plasma concentrations should be considered, if available.

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. Nilotinib does not interact with this metabolic pathway. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Paracetamol is mainly metabolised by glucuronidation (via UGTs 1A9 (major), 1A6, 1A1, and 2B15), sulfation, and to a lesser extent by oxidation (CYPs 2E1 (major), 1A2, 3A4 and 2D6). Since CYP3A4 and CYP2D6 mediated metabolism represents a minor pathway, their inhibition is unlikely to be of clinical relevance. Furthermore, there is no evidence that nilotinib inhibits or induces UGT1A9 and CYP2E1.

Coadministration has not been studied. Paroxetine is mainly metabolised by CYP2D6 and CYP3A4. Nilotinib is a potent inhibitor of CYP3A4 in vitro but only a weak inhibitor in vivo; it is a moderate inhibitor of CYP2D6 in vitro but the in vivo effect has yet to be determined. Although a clinically relevant CYP2D6 mediated interaction is unlikely, monitoring may be required. 

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. 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. Penicillins are mainly eliminated in the urine (20% by glomerular filtration and 80% by tubular secretion via OAT). Nilotinib does not interfere with elimination of penicillins.

Coadministration has not been studied. Perazine is demethylated via CYP3A4 and to a lesser extent by CYP2C9, and oxidised via FMO3. Nilotinib is a potent inhibitor of CYP3A4 in vitro but only a weak inhibitor in vivo; it also potently inhibits CYP2C9 in vitro but the in vivo effect has yet to be determined. The clinical relevance of this interaction is unknown and monitoring may be required.

Coadministration has not been studied. The metabolism of periciazine has not been well characterized but is likely to involve CYP2D6. Nilotinib is a moderate inhibitor CYP2D6 in vitro but the in vivo effect has yet to be determined. Although clinically relevant CYP2D6 mediated interactions are unlikely, monitoring may be required.

Coadministration has not been studied. Perindopril is hydrolysed to the active metabolite perindoprilat probably via CYP3A4 and is metabolised to other inactive metabolites. Elimination occurs predominantly via urine. Nilotinib is a weak inhibitor of CYP3A4 and may decrease biotransformation to active substance. As the clinical relevance of this interaction is unknown, monitoring of blood pressure may be required. 

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Perphenazine is metabolised by CYP2D6. Nilotinib is a moderate inhibitor of CYP2D6 in vitro but the in vivo effect has yet to be determined. However, clinically relevant CYP2D6 mediated interactions are unlikely. Use nilotinib with caution when coadministered with a drug with a known risk of Torsade de Pointes. In patients, therapeutic doses of nilotinib 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 metabolised mainly by CYP2B6 and to a lesser extent by CYP3A4. Nilotinib is a weak inhibitor of CYP3A4, however since CYP3A4 mediated metabolism is only a minor pathway, a clinically relevant interaction is unlikely.

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

Coadministration has not been studied and should be avoided as significant decreases in nilotinib plasma exposure may occur due to induction of CYP3A4. Decreased nilotinib exposure can lead to decreased efficacy. Selection of an alternative concomitant medication with no or minimal enzyme or transporter induction potential is recommended. If coadministration is unavoidable, the dose of nilotinib might need to be increased depending on patient tolerability. No absolute dose adjustment advice can be given, due to the non-linear pharmacokinetics. A dosing regimen more frequent than twice daily may be necessary to obtain adequate nilotinib exposure. Consider monitoring of nilotinib plasma concentrations, if available.

Coadministration has not been studied. Phenprocoumon is metabolised by CYP2C9 and CYP3A4. Nilotinib is an inhibitor of CYP2C9 in vitro and a weak inhibitor of CYP3A4 in vivo. Concentrations of phenprocoumon may increase due to inhibition of CYP2C9 and CYP3A4. Care should be taken when phenprocoumon is coadministered with nilotinib. It is recommended to monitor INR/PT if nilotinib is coadministered with anticoagulants.

Coadministration has not been studied but should be avoided. Phenytoin is mainly metabolised by CYP2C9 and to a lesser extent by CYP2C19. Nilotinib is an inhibitor of CYP2C9 and CYP2C19 in vitro and may increase concentrations of phenytoin. Monitoring for phenytoin toxicity may be necessary. Monitor phenytoin plasma concentrations, if available. Furthermore, phenytoin is a potent inducer of CYP3A4, UGT and P-gp. Concentrations of nilotinib may decrease due to CYP3A4 induction. In healthy volunteers (n=15), coadministration of nilotinib (400 mg single oral dose) and the strong CYP3A4 inducer, rifampicin (600 mg once daily for 12 days) decreased nilotinib AUC and Cmax by 80% and 64%, respectively. A similar effect may occur with phenytoin. Therefore, coadministration should be avoided. If coadministration is unavoidable, the dose of nilotinib may need to be increased depending on patient tolerability. No absolute dose adjustment advice can be given, due to the non-linear pharmacokinetics. A dosing regimen more frequent than twice daily may be necessary to obtain adequate nilotinib exposure. Consider monitoring of nilotinib 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. Nilotinib 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 metabolised by CYP3A4 and nilotinib is only a weak inhibitor of CYP3A4. However, the product labels for pimozide contraindicate its use in the presence of other drugs that prolong the QT interval, such as nilotinib. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pindolol is partly metabolised to hydroxymetabolites (possibly via CYP2D6) and partly eliminated unchanged in the urine. Nilotinib is a moderate inhibitor of CYP2D6 in vitro but the in vivo effect has yet to be determined. However, clinically relevant CYP2D6 mediated interactions are unlikely.

Coadministration has not been studied. Pioglitazone is metabolised mainly by CYP2C8 and to a lesser extent by CYPs 3A4, 1A2 and 2C9. Nilotinib is a potent inhibitor of CYP3A4 in vitro but only a weak inhibitor in vivo; it also potently inhibits CYP2C8 and CYP2C9 in vitro but the in vivo effect has yet to be determined. Concentrations of pioglitazone may increase due to CYP3A4 inhibition. As the clinically relevance of these interactions is unknown, monitoring may be required.

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. Nilotinib is a moderate inhibitor of CYP2D6 in vitro but the in vivo effect has yet to be determined. However, clinically relevant CYP2D6 mediated interactions are unlikely. Use nilotinib with caution when coadministered with a drug with a known risk of Torsade de Pointes. In patients, therapeutic doses of nilotinib have been shown to prolong the QTc interval. If coadministration is necessary, close monitoring including ECG assessment is recommended.

Coadministration has not been studied. Piroxicam is primarily metabolised by CYP2C9. Nilotinib is an inhibitor of CYP2C9 in vitro and may increase concentrations of piroxicam. As the clinical relevance of this interaction is unknown, monitoring for toxicity may be required.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pitavastatin is metabolised by UGTs 1A3 and 2B7 with minimal metabolism by CYPs 2C9 and 2C8. Nilotinib is a potent inhibitor of CYP2C9 and CYP2C8 in vitro but the in vivo effect has yet to be determined. However, since CYP2C9 and CYP2C8 mediated metabolism is only a minor pathway, a clinically relevant interaction is unlikely. 

Coadministration has not been studied and is not recommended as nilotinib concentrations may increase due to inhibition of CYP3A4 by posaconazole. Concurrent use of CYP3A4 inhibitors should be avoided as nilotinib is relatively toxic. If coadministration is unavoidable, a decrease of the nilotinib dose to 50% of the original dose should be considered. However, there are no clinical data with this dose adjustment in patients receiving CYP3A4 inhibitors. Note: Use nilotinib with caution when coadministered with a drug with a known risk of Torsade de Pointes. In patients, therapeutic doses of nilotinib have been shown to prolong the QTc interval with approximately 20 msec. Coadministration is not recommended. If coadministration is necessary, close monitoring including ECG assessment is recommended. Monitoring of nilotinib plasma concentrations should also be considered, if available.

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

Coadministration has not been studied. Prasugrel is a prodrug and is converted to its active metabolite mainly by CYP3A4 and CYP2B6. Nilotinib is a weak inhibitor of CYP3A4 and may increase concentrations of prasugrel. As the clinical relevance of this interaction is unknown, monitoring may be required.

Coadministration has not been studied. Pravastatin is minimally metabolised via CYP enzymes and is a substrate of OATP1B1. Nilotinib is an inhibitor of OATP1B1 in vitro and may increase concentrations of pravastatin. The clinically relevance of this interaction is unknown.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Prazosin is extensively metabolised, primarily by demethylation and conjugation. Nilotinib 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 to form methylprednisolone. Nilotinib is a weak inhibitor of CYP3A4 and may increase concentrations of prednisolone. However, since prednisolone has a wide therapeutic index, a clinically relevant interaction is unlikely.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Prednisone is converted to the active metabolite prednisolone by 11-B-hydroxydehydrogenase. Prednisolone is then metabolised by CYP3A4. Nilotinib is a weak inhibitor of CYP3A4 and may increase concentrations of prednisolone. However, since prednisolone has a wide therapeutic index, a clinically relevant interaction is unlikely.

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. Nilotinib is a moderate inhibitor of CYP2D6 and CYP2C19 in vitro but the vivo effect has yet to be determined. However, clinically relevant CYP2D6 and CYP2C19 mediated interactions are unlikely. Note: Nilotinib should be used with caution when coadministered with a drug that has a potential risk to prolong the QT interval. Nilotinib has been shown 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. Promethazine is metabolised by CYP2D6. Nilotinib is a moderate inhibitor of CYP2D6 in vitro but the in vivo effect has yet to be determined. However, clinically relevant CYP2D6 mediated interactions are unlikely. Use nilotinib with caution when coadministered with a drug with a known risk of Torsade de Pointes. In patients, therapeutic doses of nilotinib 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 metabolised mainly by CYP2D6 and to a lesser extent CYP1A2 and CYP3A4. Nilotinib is a potent inhibitor of CYP3A4 in vitro but only a weak inhibitor in vivo; it is a moderate inhibitor of CYP2D6 in vitro but the in vivo effect has yet to be determined. However, clinically relevant CYP2D6 mediated interactions are unlikely.

Coadministration has not been studied. Propranolol is metabolised by 3 routes (aromatic hydroxylation by CYP2D6, N-dealkylation followed by side chain hydroxylation via CYPs 1A2, 2C19, 2D6, and direct glucuronidation). Nilotinib is a moderate inhibitor of CYP2D6 and CYP2C19 in vitro but the in vivo effect has yet to be determined. Although clinically relevant CYP2D6 and CYP2C19 mediated interactions are unlikely, monitoring may be required.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Prucalopride is minimally metabolised and mainly renally eliminated, partly by active secretion by renal transporters (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 metabolised by xanthine oxidase. Nilotinib 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. Quetiapine is primarily metabolised by CYP3A4. Nilotinib is a weak inhibitor of CYP3A4 and may increase concentrations of quetiapine. 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. Quinapril is de-esterified to the active metabolite quinaprilat which is eliminated primarily by renal excretion via OAT3. Nilotinib does not interact with this renal transporter. 

Coadministration has not been studied. Quinidine is a substrate of CYP3A4 and an inhibitor of CYP2D6. Nilotinib is a weak inhibitor of CYP3A4. The clinical relevance of this interaction is unknown but caution is advised because of the narrow therapeutic index of quinidine. Furthermore, nilotinib should be used with caution when coadministered with a drug with a known risk of Torsade de Pointes. In patients, therapeutic doses of nilotinib have been shown to prolong the QTc interval with approximately 20 msec. If coadministration is necessary, close monitoring including ECG assessment is recommended.

Coadministration has not been studied. The solubility of nilotinib is pH dependent. There was a modest reduction in the rate and extent of nilotinib absorption when coadministered with esomeprazole at the 40-mg once-daily dose (AUC decreased by 34%, Cmax decreased by 27%). Although, use of proton pump inhibitors or H2 antagonists did not seem to affect the efficacy of nilotinib in patients with Ph+ CML-CP, monitoring of nilotinib plasma concentrations should be considered, if available.

Coadministration has not been studied. Ramipril is hydrolysed to the active metabolite ramiprilat probably via CYP3A4, and is metabolised to the diketopiperazine ester, diketopiperazine acid and the glucuronides of ramipril and ramiprilat. Nilotinib is a weak inhibitor of CYP3A4 and may decrease biotransformation to active substance. As the clinical relevance of this interaction is unknown, monitoring of blood pressure may be required.

Coadministration has not been studied. The solubility of nilotinib is pH dependent. No significant change in nilotinib pharmacokinetics was observed when nilotinib was administered 10 hours after and 2 hours before famotidine Therefore, when the concurrent use of a H2 blocker is necessary, it may be administered approximately 10 hours before and approximately 2 hours after the dose of nilotinib. Although, use of proton pump inhibitors or H2 antagonists did not seem to affect the efficacy of nilotinib in patients with Ph+ CML-CP, monitoring of nilotinib plasma concentrations should be considered, if available.

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. Nilotinib is an inhibitor of P-gp and CYP3A4, and may increase concentrations of ranolazine. Furthermore, ranolazine is a weak inhibitor of P-gp, CYP3A4 and CYP2D6. Concentrations of nilotinib may increase due to weak inhibition of P-gp. The clinical relevance of this interaction is unknown. No a priori dosage adjustment for nilotinib and ranolazine 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. Reboxetine is metabolised by CYP3A4. Nilotinib is a weak inhibitor of CYP3A4 and may increase concentrations of reboxetine. As the clinical relevance of this interaction is unknown, monitoring may be required.

Coadministration has not been studied. Repaglinide is metabolised by CYP2C8 and CYP3A4 with clinical data indicating it is a substrate of the hepatic transporter OATP1B1. Nilotinib is a potent inhibitor of CYP3A4 in vitro but only a weak inhibitor in vivo; it also potently inhibits CYP2C8 in vitro but the in vivo effect has yet to be determined. Concentrations of repaglinide may increase due to CYP3A4 inhibition. 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. 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. Nilotinib 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 and should be avoided as significant decreases in nilotinib plasma concentrations may occur due to induction of CYP3A4. A decrease in nilotinib exposure can lead to decreased efficacy. Selection of an alternative concomitant medication with no or minimal enzyme or transporter induction potential is recommended. If coadministration is clinically necessary, the dose of nilotinib might need to be increased depending on patient tolerability. No absolute dose adjustment advice can be given, due to the non-linear pharmacokinetics. A dosing regimen more frequent than twice daily may be necessary to obtain adequate nilotinib exposure. Consider monitoring of nilotinib plasma concentrations, if available.

Coadministration should be avoided as significant decreases in nilotinib plasma concentrations may occur due to induction of CYP3A4. In healthy volunteers, nilotinib (single dose of 400 mg) coadministered with rifampicin (600 mg once daily for 12 days) decreased the AUC and Cmax of nilotinib by 80% and 64%, respectively. A decrease in nilotinib exposure can lead to decreased efficacy. Selection of an alternative concomitant medication with no or minimal enzyme or transporter induction potential is recommended. If coadministration is clinically necessary, a dose increase dependant on patient tolerability may be required. No absolute dose adjustment advice can be given, due to the non-linear pharmacokinetics. A dosing regimen more frequent than twice daily may be necessary to obtain adequate nilotinib exposure. Consider monitoring of nilotinib plasma concentrations, if available.

Coadministration has not been studied and should be avoided as significant decreases in nilotinib plasma concentrations may occur due to induction of CYP3A4. Decrease in nilotinib exposure can lead to decreased efficacy. Selection of an alternative concomitant medication with no or minimal enzyme or transporter induction potential is recommended. If coadministration is clinically necessary, a dose increase of nilotinib dependent on patient tolerability may be required. No absolute dose adjustment advice can be given, due to the non-linear pharmacokinetics. A dosing regimen more frequent than twice daily may be necessary to obtain adequate nilotinib exposure. Consider monitoring of nilotinib plasma concentrations, if available.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Rifaximin is mainly excreted in the faeces, almost entirely as unchanged drug. Nilotinib does not interact with this metabolic pathway. 

Coadministration has not been studied. Risperidone is metabolised by CYP2D6 and to a lesser extent by CYP3A4. Risperidone is a substrate of P-gp. Nilotinib is a potent inhibitor of CYP3A4 in vitro but only a weak inhibitor in vivo; it is also a moderate inhibitor of CYP2D6 in vitro but the in vivo effect has yet to be determined. Concentrations of risperidone may potentially increase. Furthermore, nilotinib also inhibits P-gp. Monitoring may be required.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Rivaroxaban is partly metabolised in the liver (by CYP3A4, CYP2J2 and hydrolytic enzymes) and partly eliminated unchanged in urine (by P-gp and BCRP). Nilotinib is a weak inhibitor of CYP3A4 and inhibits P-gp in vitro, potentially increasing concentrations of rivaroxaban. As the clinical relevance of these interactions is unknown, monitoring may be required.

Coadministration has not been studied. Rosiglitazone is metabolised mainly by CYP2C8 and to a lesser extent CYP2C9. Nilotinib is a potent inhibitor of CYP2C8 and CYP2C9 in vitro but the in vivo effect has yet to be determined. Concentrations of rosiglitazone may increase due to inhibition of CYP2C8 and CYP2C9. As the clinical relevance of these interactions is unknown, monitoring may be required.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Rosuvastatin is largely excreted unchanged in faeces by OATP1B1. Nilotinib does not interact with this pathway. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Salbutamol is metabolised to the inactive salbutamol-4’-O-sulphate. Nilotinib 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 metabolised by CYP3A4. Nilotinib is a weak inhibitor of CYP3A4 and may increase concentrations of salmeterol. However, the systemic absorption of salmeterol after bronchial administration is low and a clinically relevant interaction is unlikely.

Coadministration has not been studied. Saxagliptin is mainly metabolised by CYP3A4 and is a substrate of P-gp. Nilotinib is a weak inhibitor of CYP3A4 and also inhibits P-gp. Therefore, concentrations of saxagliptin may increase. As the clinical relevance of these interactions is unknown, 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 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 clinically significant pharmacokinetic interaction is unlikely as sertindole is metabolised by CYP2D6 and CYP3A4. Nilotinib is a potent inhibitor of CYP3A4 in vitro but only a weak inhibitor in vivo; it is a moderate inhibitor of CYP2D6 but the in vivo effect has yet to be determined. However, clinically relevant CYP2D6 mediated interactions are unlikely. Note: The product labels for sertindole contraindicate its use in the presence of other drugs that prolong the QT interval, such as nilotinib.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Sertraline is mainly metabolised by CYP2B6 and to a lesser extent by CYPs 2C9, 2C19, 2D6 and 3A4. Nilotinib is a potent inhibitor of CYP3A4 in vitro but only a weak inhibitor in vivo; it also potently inhibits CYP2C9 in vitro but the in vivo effect has yet to be determined. Furthermore, nilotinib is a moderate inhibitor of CYP2D6 and CYP2C19 in vitro but again, the in vivo effect has yet to be determined. However, since metabolism mediated by CYPs 3A4, 2D6, 2C9 and 2C19 are minor pathways, clinically relevant interactions are unlikely.

Coadministration has not been studied. Sildenafil is metabolised mainly by CYP3A4 and to a lesser extent by CYP2C9. Nilotinib is a potent inhibitor of CYP3A4 in vitro but only a weak inhibitor in vivo; it also potently inhibits CYP2C9 in vitro but the in vivo effect has yet to be determined. As the clinical relevance of this interaction is unknown, monitoring for toxicity may be required.

Coadministration has not been studied. Simvastatin is metabolised by CYP3A4 and the metabolite is a substrate of OATP1B1. Nilotinib is a weak inhibitor of CYP3A4 and may increase concentrations of simvastatin. As the clinical relevance of this interaction is unknown, monitoring for toxicity may be required.

Coadministration has not been studied. Sirolimus is metabolised by CYP3A4 and is a substrate of P-gp. Nilotinib is a weak inhibitor of CYP3A4 and an inhibitor of P-gp in vitro and may increase sirolimus exposure. Close monitoring of 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. Sitagliptin is primarily eliminated in urine as unchanged drug (active secretion by OAT3, OATP4C1, and P-gp) and metabolism by CYP3A4 represents only a minor elimination pathway. Nilotinib is a weak inhibitor of CYP3A4 but since CYP3A4 mediated metabolism is only a minor pathway, a clinically relevant interaction is unlikely.

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 erythrocytes and tissue. Cyanogen (cyanide radicals) 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 nilotinib, or to be affected if coadministered with nilotinib. 

Coadministration has not been studied but 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 advises extreme caution if given with other drugs that prolong the QT interval, such as nilotinib. 

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. Nilotinib 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 metabolised by the flavin containing monooxygenases. Nilotinib does not interact with this metabolic pathway. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Stanozolol undergoes hepatic metabolism. Nilotinib is an inhibitor of CYPs. However, since stanozolol has a wide therapeutic index, a clinically relevant interaction is unlikely.

Coadministration has not been studied and should be avoided. St John’s wort may cause significant and unpredictable decreases in the plasma concentrations of nilotinib 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. In vitro studies suggest a role of CYP2C9 in sulfadiazine metabolism. Nilotinib is a potent inhibitor of CYP2C9 in vitro and may increase concentrations of sulfadiazine. As the clinical relevance of this interaction is unknown, monitoring for toxicity may be required.

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, use nilotinib with caution when coadministered with a drug with a known risk of Torsade de Pointes. In patients, therapeutic doses of nilotinib have been shown to prolong the QTc interval. If coadministration is necessary, close monitoring including ECG assessment is recommended.

Coadministration has not been studied. Nilotinib 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 nilotinib concentrations although only to a modest extent. No a priori dosage adjustment of nilotinib is recommended. In addition, nilotinib is a weak inhibitor of CYP3A4 and may slightly increase tacrolimus concentrations. Furthermore, use nilotinib with caution when coadministered with a drug with a known risk of Torsade de Pointes. In patients, therapeutic doses of nilotinib 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. Tadalafil is metabolised by CYP3A4. Nilotinib is a weak inhibitor of CYP3A4 and may increase concentrations of tadalafil. 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. Tamsulosin is metabolised mainly by CYP3A4 and to a lesser extent by CYP2D6. Nilotinib is a potent inhibitor of CYP3A4 in vitro but only a weak inhibitor in vivo; it is a moderate inhibitor of CYP2D6 in vitro but the in vivo effect has yet to be determined. However, since tamsulosin has a wide therapeutic index, a clinically relevant interaction is unlikely.

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. Nilotinib does not interact with this elimination pathway.

Coadministration has not been studied and is not recommended. Telithromycin may increase nilotinib concentrations due to inhibition of CYP3A4. Concurrent use of potent CYP3A4 inhibitors should be avoided as nilotinib is relatively toxic and can cause dose-related QT-prolongation. If coadministration is clinically necessary, the product labels for nilotinib recommend a dose reduction of 50%. However, there are no clinical data with this dose adjustment in patients receiving CYP3A4 inhibitors. Monitoring of nilotinib plasma concentrations should be considered, if available. 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. Telmisartan is mainly glucuronidated by UGT1A3. Nilotinib 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. Nilotinib does not interact with this metabolic pathway. 

Coadministration has not been studied. Terbinafine is metabolised by CYPs 1A2, 2C9, 3A4 and to a lesser extent by CYPs 2C8 and 2C19. Nilotinib is a potent inhibitor of CYP3A4 in vitro but only a weak inhibitor in vivo; it also potently inhibits CYP2C9 and CYP2C8 in vitro but the in vivo effect has yet to be determined. Furthermore, nilotinib is a moderate inhibitor of CYP2C19 in vitro but again, the in vivo effect has yet to be determined. Although the clinical relevance of these interactions is unknown, monitoring may be required.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Testosterone is metabolised by CYP3A4. Nilotinib is a weak inhibitor of CYP3A4 and may increase concentrations of testosterone. However, since testosterone has a wide therapeutic index, a clinically relevant interaction is unlikely.

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. Nilotinib does not interact with this elimination pathway.

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

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 clinically significant pharmacokinetic interaction is unlikely. Thioridazine is metabolised by CYP2D6 (and to a lesser extent by CYP3A4). Nilotinib is a potent inhibitor of CYP3A4 in vitro but only a weak inhibitor in vivo; it is a moderate inhibitor of CYP2D6 in vitro but the in vivo effect has yet to be determined. However, clinically relevant CYP2D6 mediated interactions are unlikely. Note: The product labels for thioridazine contraindicate its use in the presence of other drugs that prolong the QT interval, such as nilotinib. 

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, use nilotinib with caution when coadministered with a drug with a known risk of Torsade de Pointes. In patients, therapeutic doses of nilotinib 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 is transported by P-gp and undergoes extensive CYP3A4 metabolism. Ticagrelor is only a mild inhibitor of CYP3A4 and P-gp but nilotinib concentrations may be slightly increased if coadministered with ticagrelor. Furthermore, nilotinib is a weak inhibitor of CYP3A4 and inhibits P-gp in vitro, potentially increasing concentrations of ticagrelor. As the clinical relevance of these interaction is unknown, 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. Nilotinib is a moderate inhibitor of CYP2D6 in vitro but the in vivo has yet to be determined. However, the systemic absorption of timolol after ocular administration is low. Therefore, a clinically relevant interaction via CYP2D6 is unlikely. 

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. Nilotinib does not interact with this elimination pathway.

Coadministration has not been studied. Tolbutamide is mainly metabolised by CYP2C9 and to a lesser extent by CYPs 2C8 and 2C19. Nilotinib is a potent inhibitor of CYP2C8 and CYP2C9 in vitro but the in vivo effect has yet to be determined. Nilotinib moderately inhibits CYP2C19 in vitro but again, the in vivo effect has yet to be determined. Therefore, concentrations of tolbutamide may potentially increase. As the clinical relevance of these interactions is unknown, monitoring may be required.