Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. After ingestion of acarbose, the majority of active unchanged drug remains in the lumen of the gastrointestinal tract to exert its pharmacological activity and is metabolised by intestinal enzymes and by the microbial flora. 

Coadministration has not been studied but is contraindicated. Acenocoumarol is mainly metabolised by CYP2C9 and to a lesser extent by CYP1A2 and CYP2C19. Concentrations of acenocoumarol may increase due to moderate inhibition of CYP2C9. Due to known increased risks of bleeding in conjunction with the use of imatinib (e.g. haemorrhage), patients who require anticoagulation should receive low-molecular-weight or standard heparin, instead of coumarin derivatives such as acenocoumarol.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Aspirin is rapidly deacetylated to form salicylic acid and then further metabolised by glucuronidation (by several UGTs, major UGT1A6). Imatinib 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. Imatinib does not inhibit or induce CYP1A2.

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

Coadministration has not been studied. Alfentanil undergoes extensive CYP3A4 metabolism and concentrations may increase as imatinib is a moderate inhibitor of CYP3A4. Close monitoring for alfentanil toxicity is recommended.

Coadministration has not been studied. Alfuzosin is metabolised by CYP3A. Imatinib is a moderate inhibitor of CYP3A4 and may increase alfuzosin concentrations. However, since alfuzosin 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. Aliskiren is minimally metabolised and is mainly excreted unchanged in faeces. P-glycoprotein is a major determinant of aliskiren bioavailability. Imatinib is unlikely to affect aliskiren clearance.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. In vitro data indicate that alosetron is metabolised by CYPs 2C9, 3A4 and 1A2. Imatinib is a moderate inhibitor of CYP3A4 and CYP2C9 and may increase alosetron concentrations. However, due to the wide therapeutic index of alosetron, this interaction is unlikely to be clinically relevant.

Coadministration has not been studied. Alprazolam is mainly metabolised by CYP3A4. Imatinib is a moderate inhibitor of CYP3A4 and may increase alprazolam concentrations. The clinical relevance of this is interaction is unknown. Close monitoring for toxicity is recommended.

Coadministration with aluminium hydroxide alone has not been studied. Coadministration of a magnesium- and aluminium-based antacid 15 minutes prior to imatinib (400 mg single dose) had no significant effect on imatinib AUC (4% increase) or Cmax (no change) (n=12).

Coadministration has not been studied. Ambrisentan is metabolised by glucuronidation via UGTs 1A3, 1A9 and 2B7, and to a lesser extent by CYP3A4 and CYP2C19. Ambrisentan is also a substrate of P-gp. Imatinib is a moderate inhibitor of CYP3A4/5 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.

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. Imatinib is unlikely to affect amiloride renal elimination.

Coadministration has not been studied. Amiodarone is metabolized by CYPs 2C8 and 3A4. Imatinib is a moderate inhibitor of CYP3A4/5. Concentrations of amiodarone may increase due to moderate inhibition of CYP3A4 by imatinib. Close monitoring for amiodarone toxicity is recommended.

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). Imatinib is unlikely to significantly affect amisulpride elimination. 

Coadministration has not been studied. Amitriptyline is metabolised predominantly by CYP2D6 and CYP2C19. Imatinib is a weak inhibitor of CYP2D6 and may increase concentrations of amitriptyline. The clinical relevance of this interaction is unknown. 

Coadministration has not been studied. Amlodipine is metabolised by CYP3A4. Imatinib is a moderate inhibitor of CYP3A4 and may increase amlodipine concentrations. Close 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. Imatinib 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. Imatinib does not interfere with amphotericin B elimination pathway. However, the European SPC for imatinib states that concomitant use of amphothericin B and antineoplastic agents can increase the risk of renal toxicity, bronchospasm and hypotension.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Anidulafungin is not metabolised hepatically but undergoes chemical degradation at physiological temperature. 

Based on metabolism and clearance a clinically significant interaction is unlikely as antacids is unlikely to alter imatinib absorption. Coadministration of calcium carbonate (4000 mg single dose) 15 minutes prior to imatinib (400 mg single dose) was studied in 11 healthy subjects and had no significant effect on imatinib AUC (no change) or Cmax (1% increase). Coadministration of a magnesium- and aluminium-based antacid 15 minutes prior to imatinib (400 mg single dose) in 12 healthy subjects had no significant effect on imatinib AUC (4% increase) or Cmax (no change).

Coadministration has not been studied. Apixaban is metabolised by CYP3A4 and to a lesser extent by CYP1A2, CYP2C8, CYP2C9 and CYP2C19. Concentrations of apixaban may increase due to moderate inhibition of CYP3A4 and CYP2C9 by imatinib. Close monitoring for anti-Xa levels is recommended when imatinib is coadministered with apixaban.

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. Imatinib is a moderate inhibitor of CYP3A4/5 and may increase concentrations of aprepitant. Close monitoring for aprepitant toxicity is recommended. Furthermore, during treatment aprepitant is a moderate inhibitor of CYP3A4 and may increase concentrations of imatinib during the three days of coadministration. No a priori dose adjustment is recommended since the therapeutic window of imatinib is relatively large and aprepitant is only used for three days. After treatment, aprepitant is a weak inducer of CYP3A4, CYP2C9 and UGT. Concentrations of imatinib may decrease due to weak induction of CYP3A4, but this is not considered to be clinically relevant.

Coadministration has not been studied. Aripiprazole is metabolised by CYP3A4 and CYP2D6. Imatinib is a weak inhibitor of CYP2D6 and a moderate inhibitor of CYP3A4 and may increase aripiprazole concentrations. Close monitoring for aripiprazole toxicity is recommended.

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 (CYP1A2 (major) and CYP3A4, 2D6 (minor). Imatinib is a moderate inhibitor of CYP3A4 and a weak inhibitor of CYP2D6. However, since these are minor pathways, this is unlikely to be of clinical relevance.

Coadministration has not been studied. Astemizole is metabolised by CYPs 2D6, 2J2 and 3A4. Imatinib is a weak inhibitor of CYP2D6 and a moderate inhibitor of CYP3A4 and may increase concentrations of astemizole. The clinical relevance of this interaction is unknown and monitoring may be required.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely 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. Imatinib is a moderate inhibitor of CYP3A4 and an inhibitor of OATP1B1 in vitro and may increase atorvastatin concentrations. The clinical relevance of these interactions is unknown. Alternatives to atorvastatin, i.e. pravastatin or rosuvastatin, should be considered.

Coadministration has not been studied. Azathioprine is converted to 6-mercaptopurine which is metabolised analogously to natural purines. Imatinib 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 clinically significant interaction is unlikely. Azithromycin is mainly eliminated via biliary excretion and animal data suggest this may occur via P-glycoprotein and MRP2. Imatinib does not interact with this pathway. No effect on imatinib concentrations is expected. 

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. Imatinib does not interact with this pathway. 

Coadministration has not been studied. Bedaquiline is metabolised by CYP3A4. Concentrations of bedaquilline may increase due to moderate inhibition of CYP3A4 by imatinib. Close monitoring for bedaquiline toxicity is recommended.

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

Coadministration has not been studied. Bepridil is metabolised by CYP2D6 (major) and CYP3A4. Imatinib is a moderate inhibitor of CYP3A4 and a weak inhibitor of CYP2D6. Concentrations of bepridil may increase due to inhibition of CYP3A4 and CYP2D6 by imatinib. Close monitoring for bepridil toxicity is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Betamethasone is metabolised by CYP3A4. Imatinib is a moderate inhibitor of CYP3A4 and may increase betamethasone exposure. 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. In vitro data suggest that bezafibrate inhibits the renal transporter OAT1. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bisacodyl is converted to an active metabolite by intestinal and bacterial enzymes. Absorption from the gastrointestinal tract is minimal and the small amount absorbed is excreted in the urine as the glucuronide. 

Coadministration has not been. Bisoprolol is partly metabolised by CYP3A4 and CYP2D6 and partly eliminated unchanged in the urine. Imatinib is a moderate inhibitor of CYP3A4 and a weak inhibitor of CYP2D6 and may increase bisoprolol concentrations. Close monitoring of blood pressure is recommended.

Bosentan is a substrate and inducer of CYP3A4 and CYP2C9 and could potentially decrease imatinib exposure. Population pharmacokinetics of imatinib and bosentan were determined in a phase III study in patients with pulmonary arterial hypertension receiving imatinib (n=69) or placebo (n=81). Coadministration was estimated to decrease imatinib AUC by ~30% and to increase bosentan concentrations by ~50%. If coadministration is necessary, imatinib dose adjustment and monitoring of imatinib plasma concentration should be considered.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bromazepam undergoes oxidative biotransformation. Drug-drug interaction studies indicate that CYP3A4 plays a minor role in bromazepam metabolism, but other cytochromes such as CYP2D6 or CYP1A2 may play a role. Imatinib is a moderate inhibitor of CYP3A4 and a weak inhibitor of CYP2D6. However, since bromazepam does not have a narrow therapeutic index, this is unlikely to be of clinical relevance.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Budesonide is metabolised by CYP3A4. Imatinib is a moderate inhibitor of CYP3A4 and may increase budesonide exposure. However, since budesonide 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). Imatinib is a moderate CYP3A4 inhibitor and formation of the active metabolite may be reduced. The clinical relevance of this interaction is unknown. Selection of an alternate concomitant medicinal product, which is not or minimally affected by CYP3A4 inhibitors should be considered

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

Coadministration has not been studied. Buspirone is metabolised by CYP3A4. Imatinib is a moderate inhibitor of CYP3A4 and may increase buspirone concentrations. The clinical relevance of this is 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. 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. Imatinib 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. Imatinib does not interfere with captopril elimination.

Coadministration should be avoided. Carbamazepine is primarily metabolised by CYP3A4 and to a lesser extent by CYP2C8. Imatinib is a moderate inhibitor of CYP3A4 and may increase concentrations of carbamazepine. If coadministration is unavoidable, close monitoring for carbamazepine toxicity is recommended. Monitor carbamazepine plasma concentrations, if available. Furthermore, carbamazepine is an inducer of CYPs 2C8 (strong), 2C9 (strong), 3A4 (strong), 1A2 (weak), 2B6 and UGT1A1. Significant decreases in imatinib plasma exposure may occur due to induction of CYP3A4 and CYP2C9. Mean trough concentrations of imatinib decreased by ~66% in patients on carbamazepine (n=63) when compared to patients not receiving antiepileptic drugs (n=111). Decreased imatinib exposure can lead to decreased efficacy. Therefore coadministration should be avoided. Selection of an alternate concomitant medicinal product, with no or minimal potential to induce CYP3A4 should be considered. If coadministration is necessary, the US product label recommends an imatinib dosage increase of at least 50% based on pharmacokinetic studies in combination with careful monitoring of clinical response. Monitoring of imatinib plasma concentrations should be considered, if available.

Coadministration has not been studied. Carvedilol undergoes glucuronidation via UGTs 1A1, 2B4 and 2B7, and metabolism via CYP2D6 and to a lesser extent CYPs 2C9 and 1A2. Imatinib is a weak inhibitor of CYP2D6 and may increase carvedilol concentrations. 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. Caspofungin undergoes spontaneous chemical degradation and metabolism via a non CYP-mediated pathway. Imatinib does not interact with this metabolic pathway. 

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

Coadministration has not been studied. Celecoxib is primarily metabolised by CYP2C9. Concentrations of celecoxib may increase due to moderate inhibition of CYP2C9 by imatinib. Monitoring for celexocib 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. In vitro data indicate that cetirizine inhibits OCT2. Imatinib 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 imatinib via this mechanism, increasing the risk of adverse events. The clinical significance of this interaction is unknown and close monitoring is recommended. Ocular use: Although chloramphenicol is systemically absorbed when used topically in the eye, the concentrations used are unlikely to cause a clinically significant interaction. 

Coadministration has not been studied. Chlordiazepoxide is extensively metabolised by CYP3A4, but does not inhibit or induce cytochromes. Imatinib is a moderate inhibitor of CYP3A4/5. Concentrations of chlordiazepoxide may increase due to moderate inhibition of CYP3A4. Close monitoring for chlordiazepoxide toxicity is recommended.

Coadministration has not been studied. Chlorphenamine is predominantly metabolised in the liver via CYP2D6. Imatinib is a weak inhibitor of CYP2D6 and may increase chlorphenamine concentrations. The clinical relevance of this interaction is unknown. 

Coadministration has not been studied. Chlorpromazine is metabolised mainly by CYP2D6, but also by CYP1A2. Imatinib is a weak inhibitor of CYP2D6 and may increase chlorpromazine concentrations. The clinical relevance of this interaction is unknown and monitoring may be required. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. 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. Imatinib is a moderate inhibitor of CYP3A4 and may increase ciclosporin concentrations. Coadministration was shown to increase ciclosporin trough concentrations by ~94% in adult patients (n=16) and by ~78% in paediatric patients (n=6). Imatinib is metabolised mainly by CYP3A4 and inhibition of CYP3A4 by ciclosporin could potentially increase imatinib concentrations. The ciclosporin dose should be decreased dependent on the indication and protocol involved, and monitoring of ciclosporin plasma concentrations is recommended. No a priori dosage adjustment is recommended for imatinib, but close monitoring of toxicity is recommended. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cilazapril is mainly eliminated unchanged by the kidneys. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. In vitro data indicate that cimetidine inhibits OAT1 and OCT2 but at concentrations much higher than the observed clinical concentrations. Imatinib does not interact with this pathway. Although cimetidine is an inhibitor of CYP3A4, no clinically significant effect on imatinib is expected.

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. Imatinib does not interfere with the elimination of ciprofloxacin. However, ciprofloxacin is a weak to moderate inhibitor of CYP3A4 and a strong inhibitor of CYP1A2. Imatinib concentrations may increase due to inhibition of CYP3A4. In healthy volunteers (n=14), coadministration of imatinib (200 mg single dose) and the strong CYP3A4 inhibitor, ketoconazole (400 mg single dose), increased imatinib Cmax and AUC by 26% and 40%, respectively. If coadministration is unavoidable, close monitoring for toxicity is recommended. No a priori dose adjustment is recommended since the therapeutic index of imatinib is relatively high. Monitoring of imatinib plasma concentrations should be considered, if available.

Coadministration has not been studied. Cisapride is metabolised by CYP3A4. Imatinib is a moderate inhibitor of CYP3A4 and may increase cisapride exposure. Close monitoring of cisapride toxicity is recommended. Cisapride is unlikely to alter imatinib absorption.

Coadministration has not been studied. Citalopram is metabolised by CYPs 2C19 (38%), 2D6 (31%) and 3A4 (31%). Imatinib is a weak inhibitor of CYP2D6 and a moderate inhibitor of CYP3A4 and may increase citalopram concentrations. The clinical relevance of this interaction is unknown. As multiple metabolic pathways play a role, no a priori dose adjustment of citalopram is needed. However, monitoring for toxicity may be required.

Coadministration has not been studied and is not recommended. Clarithromycin may increase imatinib concentrations due to inhibition of CYP3A4 and P-gp. Concurrent use of potent CYP3A4 inhibitors should be avoided. If coadministration is unavoidable, close monitoring of toxicity is recommended. No a priori dose adjustment is recommended since the therapeutic index of imatinib is relatively wide. Monitoring of imatinib plasma concentrations should be considered, if available.

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. Imatinib does not interact with this 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. Imatinib is a weak inhibitor of CYP2D6 and may increase clemastine concentrations. However, this is unlikely to be of clinical relevance as clemastine has a wide therapeutic index. 

Coadministration has not been studied. Clindamycin is metabolised by CYP3A4. Imatinib is a moderate inhibitor of CYP3A4 and may increase clindamycin concentrations. Close monitoring for clindamycin toxicity is recommended.

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 clinically significant interaction is unlikely. Clofazimine is largely excreted unchanged in the faeces, both as unabsorbed drug and via biliary excretion. Imatinib does not interact with this metabolic pathway. 

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. Imatinib 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. Imatinib is a weak inhibitor of CYP2D6 and a moderate inhibitor of CYP3A4. The clinical relevance of this interaction is unknown. As multiple metabolic pathways play a role in formation and metabolism of the active metabolite, no a priori dose adjustment of clomipramine is needed. However, monitoring may be required.

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

Coadministration has not been studied. Clopidogrel is a prodrug and is converted to its active metabolite via CYPs 3A4, 2B6, 2C19 and 1A2. Concentrations of the active metabolite may decrease due to moderate inhibition of CYP3A4 by imatinib and a subtherapeutic effect may occur. Selection of an alternate concomitant medicinal product, with no or minimal potential to interact with the bioactivation of clopidogrel should be considered. If coadministration is unavoidable, close monitoring for clopidogrel efficacy is recommended. 

Coadministration has not been studied. Clorazepate is rapidly converted to nordiazepam which is then metabolised to oxazepam by CYP3A4. Imatinib is a moderate inhibitor of CYP3A4. The clinical relevance of this is interaction is unknown. Close monitoring for toxicity is recommended.

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

Coadministration has not been studied. Clozapine is metabolised mainly by CYP1A2 and CYP3A4, and to a lesser extent by CYP2C19 and CYP2D6. Imatinib is a moderate inhibitor of CYP3A4 and a weak inhibitor of CYP2D6 and may increase clozapine concentrations. Close monitoring for clozapine toxicity is recommended when imatinib is coadministered with clozapine. Furthermore, due to the risk of additive haematological toxicity, haematological parameters should be monitored if coadministered.

Coadministration has not been studied. Codeine is converted via CYP2D6 to morphine, an active metabolite with analgesic and opioid properties. Morphine is further metabolised by conjugation with glucuronic acid to morphine-3-glucuronide (inactive) and morphine-6-glucuronide (active). Morphine is also a substrate of P-gp. Furthermore, codeine is converted via CYP3A4 to norcodeine, an inactive metabolite. Imatinib is a weak inhibitor of CYP2D6 and a moderate inhibitor of CYP3A4. 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. Imatinib is a moderate inhibitor of CYP3A4 and may increase colchicine concentrations. Close monitoring for colchicine toxicity is recommended.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dabigatran is transported via P-gp and is renally excreted. Imatinib does not inhibit or induce P-gp.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dalteparin is excreted largely unchanged via the kidneys. Imatinib does not interfere with the renal excretion of dalteparin. 

Coadministration has not been studied. Metabolism of dapsone is mainly by N-acetylation with a component of N-hydroxylation, and is via multiple CYP P450 enzymes. Imatinib is a moderate inhibitor of CYP3A4 and CYP2C9 and a weak inhibitor of CYP2D6. The clinical relevance of this interaction is unknown as dapsone is metabolised via multiple enzymes.

Coadministration has not been studied. Desipramine is metabolised by CYP2D6. Imatinib is a weak inhibitor of CYP2D6 and may increase concentration of desipramine. The clinical relevance of this interaction is unknown and monitoring may be required.

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. Imatinib is a moderate inhibitor of CYP3A4 and CYP2C9 and may affect the conversion of desogestrel to its active form. The clinical relevance of this interaction is unknown. Selection of an alternate concomitant medicinal product, which is not or minimally affected by CYP2C9 inhibitors should be considered.

Coadministration has not been studied. Dexamethasone has been described as an inducer of CYP3A4 and could possibly decrease imatinib plasma concentrations, but the clinical significance of CYP3A4 induction by dexamethasone has not been established yet. Monitoring of imatinib plasma concentrations should be considered, if available. 

Coadministration has not been studied. Dextropropoxyphene is mainly metabolised by CYP3A4. Imatinib is a moderate inhibitor of CYP3A4 and may increase dextropropoxyphene concentrations. Monitoring for dextropropoxyphene 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). Imatinib does not inhibit or induce UGTs.

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 2C19) and to temazepam (mainly by CYP3A4). Imatinib is a moderate inhibitor of CYP3A4 and may increase diazepam concentrations. The clinical relevance of this is interaction is unknown. Close monitoring for toxicity is recommended.

Coadministration has not been studied. Diclofenac is partly glucuronidated by UGT2B7 and partly oxidised by CYP2C9.  Concentrations of diclofenac may increase due to moderate inhibition of CYP2C9 by imatinib. Monitoring for diclofenac toxicity may be required.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Digoxin is eliminated renally via the renal transporters OATP4C1 and P-gp. Imatinib does not interfere with digoxin elimination. 

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. Imatinib is a moderate inhibitor of CYP3A4; however, since CYP3A4 mediated metabolism is a minor pathway, this is unlikely to be of clinical relevance.

Coadministration has not been studied and should be avoided. Diltiazem is metabolised by CYP3A4 and CYP2D6. Imatinib is a moderate inhibitor of CYP3A4 and a weak inhibitor of CYP2D6 and may increase diltiazem concentrations. The clinical relevance of this interaction is unknown. Diltiazem is a moderate inhibitor of CYP3A4 and could potentially increase imatinib exposure. Concurrent use of diltiazem and imatinib should be avoided. If coadministration is unavoidable, close monitoring for toxicity is recommended. No a priori dose adjustment is recommended since the therapeutic index of imatinib is relatively wide. Monitoring of imatinib plasma concentrations should be considered, if available.

Coadministration has not been studied. Diphenhydramine is mainly metabolised by CYP2D6. Imatinib is a weak inhibitor of CYP2D6 and may increase diphenhydramine 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. Dipyridamole is glucuronidated by many UGTs, specifically those of the UGT1A subfamily. Imatinib does not interact with UGTs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Disopyramide is metabolized by CYP3A4 (25%) and 50% of the drug is eliminated unchanged in the urine. Imatinib is a moderate inhibitor of CYP3A4; however, since CYP3A4 mediated metabolism is a minor pathway, this is unlikely to be of clinical relevance.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dolasetron is converted by carbonyl reductase to its active metabolite, hydrodolasetron, which is mainly glucuronidated (60%) and metabolised by CYP2D6 (10-20%) and CYP3A4 (<1%). Imatinib is a moderate inhibitor of CYP2D6 and CYP3A4. However, since CYP-medicated metabolism is only a minor pathway, a clinically relevant interaction is unlikely. 

Coadministration has not been studied. Domperidone is mainly metabolised by CYP3A4. Imatinib is a moderate inhibitor of CYP3A4 and may increase domperidone concentrations. Monitoring of domperidone toxicity 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 imatinib, or to be affected if co-administered with imatinib.

Coadministration has not been studied. Doxazosin is metabolised mainly by CYP3A4. Imatinib is a moderate inhibitor of CYP3A4 and may increase concentrations of doxazosin. Close monitoring of blood pressure is recommended. 

Coadministration has not been studied. 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. Imatinib is a weak inhibitor of CYP2D6. The clinical relevance of this interaction is unknown and monitoring may be required.

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

Coadministration has not been studied. Dronabinol is mainly metabolised by CYP2C9 and to a lesser extent by CYP3A4. Imatinib is a moderate inhibitor of CYP3A4 and CYP2C9 and may increase exposure to dronabinol. The clinical significance of this interaction is unknown.

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. Imatinib is a moderate inhibitor of CYP3A4 and may increase drospirenone concentrations. However since CYP3A4 mediated metabolism is a minor pathway, this is unlikely to be of clinical relevance.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as dulaglutide is degraded by endogenous endopeptidases. Dulaglutide delays gastric emptying and could possibly decrease the absorption rate of concomitantly administered oral drugs. Since imatinib is absorbed within 4h, the clinical relevance of delayed absorption is considered to be limited.

Coadministration has not been studied. Duloxetine is metabolised by CYP2D6 and CYP1A2. Imatinib is a weak inhibitor of CYP2D6 and may increase concentrations of duloxetine. The clinical relevance of this interaction is unknown and monitoring may be required.

Coadministration has not been studied. Dutasteride is mainly metabolised by CYP3A4. Imatinib is a moderate 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). Imatinib is a moderate inhibitor of CYP3A4 and may increase dydrogesterone concentrations. However since CYP3A4 mediated metabolism is a minor pathway, this is unlikely to be of clinical relevance.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Edoxaban is transported via P-gp. Imatinib is unlikely to interfere with this pathway.

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

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

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 excreted predominantly renally. Imatinib does not interact with this metabolic pathway.

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

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Ertapenem is mainly eliminated through the kidneys by glomerular filtration with tubular secretion playing a minor component. Imatinib does not interact with this metabolic pathway.

Coadministration has not been studied and is not recommended. Erythromycin may increase imatinib concentrations due to inhibition of CYP3A4. Concurrent use of potent CYP3A4 inhibitors should be avoided. If coadministration is unavoidable, close monitoring of toxicity is recommended. No a priori dose adjustment is recommended since the therapeutic index of imatinib is relatively wide. Monitoring of imatinib plasma concentrations should be considered, if available.

Coadministration has not been studied. Escitalopram is metabolised by CYP2C19 (37%), 2D6 (28%) and 3A4 (35%) to form N-desmethylescitalopram. Imatinib is a weak inhibitor of CYP2D6 and a moderate inhibitor of CYP3A4 and may increase escitalopram concentrations. The clinical relevance of this interaction is unknown. As multiple metabolic pathways play a role, no a priori dose adjustment of citalopram is needed, however, monitoring for toxicity may be required.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Imatinib is freely soluble up to a pH of 5.5 and no clinically significant effect of gastric pH increasing drugs on imatinib exposure is expected. Esomeprazole is metabolised by CYP2C19 and CYP3A4 and inhibits CYP2C19. Imatinib is a moderate inhibitor of CYP3A4 and may increase esomeprazole concentrations. However, since esomeprazole has a wide therapeutic index, this is unlikely to be clinically relevant.

Coadministration has not been studied. Estazolam is metabolised to its major metabolite 4-hydroxyestazolam via CYP3A4. Imatinib is a moderate inhibitor of CYP3A4 and may increase estazolam concentrations. The clinical relevance of this is 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. Estradiol is metabolised by CYP3A4, CYP1A2 and is glucuronidated. Imatinib is a moderate inhibitor of CYP3A4 and may increase estradiol concentrations. However since CYP3A4 mediated metabolism is a minor pathway, this is unlikely to be of clinical relevance.

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 in the urine (50%). Imatinib does not interact with this metabolic pathway.

Coadministration has not been studied. Ethinylestradiol undergoes oxidation (CYP3A4>CYP2C9), sulfation and glucuronidation (UGT1A1). Imatinib is a moderate inhibitor of CYP3A4 and CYP2C9 and may increase ethinylestradiol concentrations. The clinical significance of this interaction is unknown.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Etonogestrel is metabolised by CYP3A4. Imatinib is a moderate inhibitor of CYP3A4 and may increase etonogestrel concentrations. However, since etonogestrel does not have a narrow therapeutic index, this is unlikely to be of clinical relevance.

Imatinib is primarily metabolised by CYP3A4 and to a lesser extent by CYPs 1A2, 2D6, 2C9 and 2C19. Everolimus does not inhibit or induce these CYPs. Imatinib is also a substrate of P-gp and concentrations may increase due to mild inhibition of P-gp by everolimus, but this is unlikely to be of clinical significance. In vitro data indicate that imatinib is an inhibitor of CYPs 3A4, 2D6, 2C9 and 2C19 and could potentially increase everolimus exposure by inhibition of CYP3A4. In patients with gastrointestinal stromal tumours (n=12), coadministration of imatinib (600 mg once daily for two months) and everolimus (20 mg once weekly for 2 months) increased everolimus AUC and Cmax by 3.7-fold and 2.2-fold, respectively. Since everolimus as an immunosuppressant is dosed much lower than as an anticancer therapy, the clinical relevance of this interaction is unknown. No a priori dosage adjustment is recommended for everolimus. Monitoring of everolimus tolerability is recommended. Due to the risk of additive haematological toxicity, haematological parameters should be monitored if coadministered.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as exenatide is cleared mainly by glomerular filtration. Exenatide delays gastric emptying and could possibly decrease the absorption rate of concomitantly administered oral drugs. Since imatinib is absorbed in within 4h, 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. Imatinib does not interact with this pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Imatinib is freely soluble up to a pH of 5.5 and no clinically significant effect of gastric pH increasing drugs on imatinib exposure is expected.

Coadministration has not been studied. Felodipine is metabolised by CYP3A4. Imatinib is a moderate inhibitor of CYP3A4 and may increase felodipine concentrations. Close 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. In vitro data suggest that fenofibric acid inhibits OAT3. Imatinib does not interact with this pathway.

Coadministration has not been studied. Fentanyl undergoes extensive CYP3A4 metabolism. Imatinib is a moderate inhibitor of CYP3A4 and may increase fentanyl concentrations. Close monitoring for fentanyl 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. Finasteride is metabolised by CYP3A4. Imatinib is a moderate inhibitor of CYP3A4 and may increase finasteride concentrations. 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. Flecainide is metabolized mainly via CYP2D6, with a proportion (approximately 30%) of the parent drug also eliminated unchanged renally. Imatinib is a weak inhibitor of CYP2D6 and may increase flecainide concentrations. Close monitoring for flecainide toxicity is recommended as it has a narrow therapeutic index.

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

Coadministration has not been studied. Imatinib concentrations may increase due to inhibition of CYP3A4 by fluconazole. However, no clinically relevant interaction is expected since therapeutic levels of fluconazole are approximately 8-fold lower than the observed IC50s for CYP3A4. However, this possibility cannot be discarded in at-risk patients as for example hepatically impaired patients. No a priori dose adjustment for imatinib is recommended since the therapeutic index of imatinib is relatively high. Monitoring of imatinib 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. Imatinib 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. Imatinib 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. Imatinib is a moderate inhibitor of CYP3A4 and may increase fludrocortisone exposure. However, since fludrocortisone has a wide therapeutic index, a clinically relevant interaction is unlikely.

Coadministration has not been studied. Flunitrazepam is metabolised mainly via CYPs 3A4 and 2C19. Imatinib is a moderate inhibitor of CYP3A4 and may increase flunitrazepam concentrations. Monitoring of toxicity may be required.

Coadministration has not been studied. Fluoxetine is metabolised by CYPs 2D6 and 2C9 and to a lesser extent by 2CYPs 2C19 and 3A4 to form norfluoxetine. Imatinib is a weak inhibitor of CYP2D6 and a moderate inhibitor of CYP2C9 and CYP3A4 and may increase fluoxetine concentrations. The clinical relevance of this interaction is unknown and close monitoring for toxicity is recommended.

Coadministration has not been studied. Fluphenazine is metabolised by CYP2D6. Imatinib is a weak inhibitor of CYP2D6 and may increase fluphenazine concentrations. The clinical relevance of this interaction is unknown and monitoring may be required. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. The metabolism of flurazepam is most likely CYP-mediated. Imatinib is a moderate inhibitor of CYP3A4 and CYP2C9 and may increase flurazepam concentrations. Monitoring of toxicity may be required.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fluticasone is metabolised by CYP3A4. Imatinib is a moderate inhibitor of CYP3A4 and may increase hydrocortisone exposure. 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. Imatinib is a moderate inhibitor of CYP2C9 and may increase fluvastatin concentrations. It is recommended to start with the lowest dose of fluvastatin and titrate up to the desired clinical effect while monitoring for safety.

Coadministration has not been studied. Fluvoxamine is metabolised mainly by CYP2D6 and to a lesser extent by CYP1A2. Imatinib is a weak inhibitor of CYP2D6 and may increase fluvoxamine concentrations. Fluvoxamine inhibits CYPs 1A2, 2C19, 3A4, 2C9 and may slightly increase imatinib concentrations. The clinical relevance of these interactions is unknown and monitoring may be required.

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

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

Coadministration has not been studied but should be approached with caution. Fosaprepitant is rapidly, almost completely, converted to the active metabolite aprepitant. Imatinib does not interact with this metabolic pathway. Aprepitant is mainly metabolised by CYP3A4 and to a lesser extent by CYP1A2 and CYP2C19. Imatinib is a moderate inhibitor of CYP3A4/5 and may increase concentrations of aprepitant. Close monitoring for aprepitant toxicity is recommended. Furthermore, during treatment aprepitant is a moderate inhibitor of CYP3A4 and may increase concentrations of imatinib during the three days of coadministration. No a priori dose adjustment is recommended since the therapeutic window of imatinib is relatively large and aprepitant is only used for three days. After treatment, aprepitant is a weak inducer of CYP3A4, CYP2C9 and UGT. Concentrations of imatinib may decrease due to weak induction of CYP3A4, but this is not considered to be clinically relevant. Monitoring of imatinib plasma concentrations should be considered, if available.

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. Imatinib is a moderate inhibitor of CYP2C9 and may increase concentrations of phenytoin. Close monitoring for phenytoin toxicity is recommended. Furthermore, phenytoin is a potent inducer of CYP3A4, UGT and P-gp. Concentrations of imatinib may decrease due to induction of CYP3A4. Mean trough concentrations of imatinib decreased by ~73% in patients on phenytoin (n=15) when compared to patients not receiving antiepileptic drugs (n=111). In one patient within a clinical study, the AUC of a 350 mg dose of imatinib in combination with phenytoin was comparable to a dose of 85 mg imatinib monotherapy. A decrease in exposure can lead to decreased efficacy. Therefore, coadministration should be avoided. Selection of an alternate concomitant medicinal product, with no or minimal potential to induce CYP3A4 should be considered. If coadministration is necessary, the US product label recommends an imatinib dosage increase of at least 50% based on pharmacokinetic studies in combination with careful monitoring of clinical response. Monitoring of imatinib plasma concentrations should be considered, if available.

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

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

Coadministration of gemfibrozil (600 mg twice daily) and imatinib (200 mg single dose) was studied in 10 healthy subjects. Imatinib Cmax and AUC decreased by 35% and 23%, probably by inhibition of transporters OATP1A2 and OATP2B1. However, this is unlikely to be clinically significant. Gemfibrozil is metabolised by UGT2B7. Imatinib 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. Imatinib does not interact with this elimination 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. Imatinib is a moderate inhibitor of CYP3A4 and may increase gestodene concentrations. However, since gestodene does not have a narrow therapeutic index, this is unlikely to be of clinical relevance.

Coadministration has not been studied. Glibenclamide is mainly metabolised by CYP3A4 and to a lesser extent by CYP2C9. Imatinib is a moderate inhibitor of CYP3A4 and CYP2C9 and may increase glibenclamide concentrations. Close monitoring of blood glucose levels may be required.

Coadministration has not been studied. Gliclazide is metabolised mainly by CYP2C9 and to a lesser extent by CYP2C19. Imatinib is a moderate inhibitor of CYP2C9 and may increase gliclazide concentrations. Close monitoring of blood glucose levels may be required.

Coadministration has not been studied. Glimepiride is mainly metabolised by CYP2C9. Imatinib is a moderate inhibitor of CYP2C9 and may increase glimepiride concentrations. Close monitoring of blood glucose levels may be required.

Coadministration has not been studied. Glipizide is mainly metabolised by CYP2C9. Imatinib is a moderate inhibitor of CYP2C9 and may increase glipizide concentrations. Close monitoring of blood glucose levels may be required.

Coadministration has not been studied. Granisetron is metabolised by CYP3A4 and is a substrate of P-gp. Imatinib is a moderate inhibitor of CYP3A4 and may increase granisetron concentrations. Monitoring for toxicity may be required.

Grapefruit juice is known to inhibit CYP3A4 enzymes and could potentially increase imatinib concentrations. In a clinical study 250 ml per day of grapefruit juice had no significant effect on imatinib pharmacokinetics in CML patients (n=4). However, the magnitude of this potential interaction is difficult to predict as the effect of grapefruit juice is concentration-, dose- and preparation-dependent and varies widely across brands. The US product label for imatinib 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. Imatinib does not interfere with griseofulvin elimination pathway. However, griseofulvin is a liver microsomal enzyme inducer and may lower plasma levels, and therefore reduce the efficacy, of concomitantly administered medicinal products metabolised by CYP3A4, such as imatinib. 

Coadministration has not been studied. Haloperidol has a complex metabolism as it undergoes glucuronidation (UGT2B7>1A4, 1A9), carbonyl reduction as well as oxidative metabolism (CYP3A4, 2D6). Imatinib is a weak inhibitor of CYP2D6 and a moderate inhibitor of CYP3A4 and may increase haloperidol concentrations. The clinical relevance of this interaction is unknown and monitoring may be required. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Heparin is thought to be eliminated via the reticuloendothelial system. Imatinib 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 imatinib. 

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. In vitro data indicate that hydrochlorothiazide is unlikely to inhibit OAT1 in the range of clinically relevant concentrations. Significant interactions are not expected with imatinib.

Coadministration has not been studied. Hydrocodone is metabolised by CYP2D6 to hydromorphone and by CYP3A4 to norhydrocodone, both of which have analgesic effects. Imatinib is a moderate inhibitor of CYP3A4 and may increase hydrocodone concentrations. Close monitoring for hydrocodone toxicity is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Hydrocortisone is metabolised by CYP3A4. Imatinib is a moderate inhibitor of CYP3A4 and may increase hydrocortisone exposure. 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. Imatinib 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, 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. Hydroxyzine is partly metabolised by alcohol dehydrogenase and partly by CYP3A4. Imatinib is a moderate inhibitor of CYP3A4 and may increase hydroxyzine concentrations. However, since hydroxyzine does not have a narrow therapeutic index and does have an alternative metabolic pathway, this is unlikely to be of clinical relevance.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ibandronic acid is not metabolised and is cleared from the plasma by uptake into bone and elimination via renal excretion. 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. Ibuprofen is metabolised mainly by CYP2C9 and to a lesser extent by CYP2C8 and direct glucuronidation. Imatinib is a moderate inhibitor of CYP2C9 and may increase ibuprofen concentrations. However, ibuprofen has a broad therapeutic index and a clinically relevant interaction is unlikely.

Coadministration has not been studied. Iloperidone is metabolised by CYP3A4 and CYP2D6. Imatinib is a weak inhibitor of CYP2D6 and a moderate inhibitor of CYP3A4 and may increase iloperidone concentrations. The clinical relevance of this interaction is unknown and monitoring may be required. 

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

Coadministration has not been studied. Imipramine is metabolised by CYP2D6 (major) and CYPs 3A4, 2C19 and 1A2 (minor) to desipramine. Imipramine and desipramine are both metabolised by CYP2D6. Imatinib is a weak inhibitor of CYP2D6 and a moderate inhibitor of CYP3A4. The clinical relevance of this interaction is unknown. As multiple metabolic pathways play a role, no a priori dose adjustment of imipramine is needed, however, monitoring for toxicity may be required.

Coadministration has not been studied. Indapamide is extensively metabolised by CYP P450. Imatinib is a moderate inhibitor of CYP3A4 and CYP2C9 and a weak inhibitor of CYP2D6. The clinical relevance of this interaction is unknown and monitoring of blood pressure may be required.

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

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Interleukin-2 is mainly eliminated by glomerular filtration. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. A small proportion of an inhaled ipratropium dose is systemically absorbed (6.9%). Metabolism is via ester hydrolysis and conjugation. Imatinib does not interact with this metabolic pathway.

Coadministration has not been studied. Irbesartan is metabolised by glucuronidation and oxidation (mainly CYP2C9). Imatinib is a moderate inhibitor of CYP2C9 and may increase irbesartan concentrations. Close monitoring of blood pressure 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 clinically significant interaction is unlikely. Isoniazid is acetylated in the liver to form acetylisoniazid which is then hydrolysed to isonicotinic acid and acetylhydrazine. Imatinib does not interact with this metabolic pathway. 

Coadministration has not been studied but based. In vitro studies suggest that CYP3A4 has a role in nitric oxide formation from isosorbide dinitrate. Imatinib is a moderate inhibitor of CYP3A4. The clinical relevance of this interaction is unknown. 

Coadministration has not been studied and is not recommended as imatinib concentrations may increase due to inhibition of CYP3A4 by itraconazole. Concurrent use of CYP3A4 inhibitors should be avoided. If coadministration is unavoidable, close monitoring of toxicity is recommended. No a priori dose adjustment is recommended since the therapeutic index of imatinib is relatively high. Monitoring of imatinib plasma concentrations should be considered, if available.

Coadministration has not been studied. Ivabradine is metabolised by CYP3A4. Imatinib is a moderate inhibitor of CYP3A4 and may increase ivabradine concentrations. Close monitoring of blood pressure is recommended.

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 may increase imatinib concentrations due to inhibition of CYP3A4 by ketoconazole. Imatinib Cmax and AUC increased by 26% and 40% when coadministered with a single dose of ketoconazole to healthy subjects. If coadministration is unavoidable, close monitoring of toxicity is recommended. No a priori dose adjustment is recommended since the therapeutic index of imatinib is relatively high. Monitoring of imatinib plasma concentrations should be considered, if available.

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

Coadministration has not been studied. Lacidipine is metabolised by CYP3A4. Imatinib is a moderate inhibitor of CYP3A4 and may increase lacidipine concentrations. Close monitoring of blood pressure is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metabolism of lactulose to lactic acid occurs via gastro-intestinal microbial flora only. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Imatinib is freely soluble up to a pH of 5.5 and no clinically significant effect of gastric pH increasing drugs on imatinib exposure is expected. Lansoprazole is mainly metabolised by CYP2C19 and to a lesser extent by CYP3A4. Imatinib is a moderate inhibitor of CYP3A4 and may increase lansoprazole concentrations. However, since lansoprazole has a wide therapeutic index, this is unlikely to be clinically relevant.

Coadministration has not been studied. Lercanidipine is mainly metabolised by CYP3A4. Imatinib is a moderate inhibitor of CYP3A4 and may increase lercanidipine concentrations. Close monitoring of blood pressure is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Less than 14% of a dose of levocetirizine is metabolised and it 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 clinically significant interaction is unlikely. Levofloxacin is eliminated renally mainly by glomerular filtration and active secretion (possibly OCT2). Imatinib does not interact with this metabolic pathway. 

Coadministration has not been studied. Levomepromazine is metabolised by CYP2D6. Imatinib is a weak inhibitor of CYP2D6 and may increase levomepromazine concentrations. The clinical relevance of this interaction is unknown and monitoring may be required. 

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

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. Imatinib is a moderate inhibitor of CYP3A4 and may increase levonorgestrel concentrations. However, since levonorgestrel does not have a narrow therapeutic index, this is unlikely to be of clinical relevance.

Levothyroxine is metabolised by deiodination (by enzymes of deiodinase family) and glucuronidation. A case study reported that the response to levothyroxine therapy may be decreased in patients when imatinib is co-administered (mechanism unknown). Therefore, patients may need higher doses of levothyroxine. Close monitoring of TSH levels is recommended.

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

Coadministration has not been studied. Linagliptin is mainly eliminated as parent compound in faeces with metabolism by CYP3A4 representing a minor elimination pathway. Imatinib is a moderate inhibitor of CYP3A4, however since CYP3A4 mediated metabolism is a minor pathway, any increase in linagliptin is unlikely to be of clinical relevance. Linagliptin is a substrate of P-gp and is an inhibitor of CYP3A4. Imatinib concentrations may increase due to inhibition of CYP3A4 by linagliptin. If coadministration is unavoidable, close monitoring of toxicity is recommended. No a priori dose adjustment is recommended since the therapeutic index of imatinib is relatively wide. Monitoring of imatinib plasma concentrations should be considered, if available.

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 clinically significant interaction is unlikely. Lithium is mainly eliminated unchanged through the kidneys. Lithium is freely filtered at a rate that is dependent upon the glomerular filtration rate therefore no pharmacokinetic interaction is expected. 

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 and is a substrate of P-gp. Imatinib does not affect P-gp but is a moderate inhibitor of CYP3A4 and may increase loperamide concentrations. However, since loperamide has a wide therapeutic index, this is unlikely to be clinically relevant. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Loratadine is metabolised mainly by CYP3A4 and to a lesser extent by CYP2D6. Imatinib is a moderate inhibitor of CYP3A4 and a weak inhibitor of CYP2D6 and may increase loratadine concentrations. However, this is unlikely to be of clinical relevance as 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 imatinib. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lormetazepam is mainly glucuronidated. Imatinib does not induce or inhibit UGTs.

Coadministration has not been studied. Losartan is converted to its active metabolite mainly by CYP2C9 in the range of clinical concentrations. Imatinib is a moderate inhibitor of CYP2C9 and may decrease biotransformation to active substance. The clinical relevance of this interaction is unknown and close monitoring of blood pressure is recommended.

Coadministration has not been studied. Lovastatin is metabolised by CYP3A4. Imatinib is a moderate inhibitor of CYP3A4 and may increase concentrations of lovastatin. The clinical relevance of this interaction is unknown. It is recommended to start with the lowest dose of lovastatin and titrate up to the desired clinical effect while monitoring for safety.

Coadministration has not been studied. Macitentan is metabolised mainly by CYP3A4 and to a lesser extent by CYPs 2C19, 2C9 and 2C8. Imatinib is a moderate inhibitor of CYP3A4 and CYP2C9 and may increase macitentan concentrations. Close monitoring of blood pressure is recommended.

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. Maprotiline is mainly metabolised by CYP2D6. Imatinib is a weak inhibitor of CYP2D6 and may increase concentrations of maprotiline. The clinical relevance of this interaction is unknown and monitoring may be required.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Medroxyprogesterone is metabolised by CYP3A4. Imatinib is a moderate inhibitor of CYP3A4 and may increase medroxyprogesterone concentrations. However, since medroxyprogesterone does not have a narrow therapeutic index, this is unlikely to be of clinical relevance.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Medroxyprogesterone is metabolised by CYP3A4. Imatinib is a moderate inhibitor of CYP3A4 and may increase medroxyprogesterone concentrations. However, since medroxyprodesterone does not have a narrow therapeutic index, this is unlikely to be of clinical relevance.

Coadministration has not been studied. Mefenamic acid is metabolised by CYP2C9 and glucuronidated by UGT2B7 and UGT1A9. Imatinib is a moderate inhibitor of CYP2C9 and may increase mefenamic acid 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. Megestrol acetate is mainly eliminated in the urine. 

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

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

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

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). Imatinib does not interact with metformin metabolic and elimination pathways.

Coadministration has not been studied. Methadone is demethylated by CYP3A4. Imatinib is a moderate inhibitor of CYP3A4 and may increase methadone concentrations. Close monitoring for methadone toxicity 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 imatinib, or to be altered by coadministration with imatinib.

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. Imatinib is a moderate inhibitor of CYP3A4 and may increase methylprednisolone exposure. 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 CYP450 system (mainly CYP2D6). Imatinib is a moderate inhibitor of CYP2D6 and may increase metoclopramide concentrations. However, since CYP-medicated 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. 

Metoprolol is mainly metabolised by CYP2D6 and imatinib is a weak inhibitor of CYP2D6. Coadministration of imatinib (400 mg twice daily) and metoprolol increased metoprolol Cmax and AUC by ~23% due to inhibition of CYP2D6. No a priori dose adjustment is necessary; however, caution is recommended as metoprolol has a narrow therapeutic index. Monitoring of blood pressure is recommended.

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 imatinib cannot be excluded and close monitoring is recommended.

Coadministration has not been studied. Mexiletine is metabolised mainly by CYP2D6 and to a lesser extent CYP1A2. Imatinib is a weak inhibitor of CYP2D6 and may increase mexiletine concentrations. Monitoring for mexiletine toxicity maybe required.

Coadministration has not been studied. Mianserin is metabolised by CYPs 2D6 and 1A2, and to a lesser extent by CYP3A4. Imatinib is a weak inhibitor of CYP2D6 and a moderate inhibitor of CYP3A4 and may increase mianserin concentrations. The clinical relevance of this interaction is unknown and monitoring may be required.

Coadministration has not been studied. Miconazole inhibits CYP2C9 and CYP3A4 and could potentially increase imatinib concentrations. Oromucosal coadministration may increase imatinib concentrations due to inhibition of CYP3A4. Concurrent use of CYP3A4 inhibitors should be avoided. If coadministration is unavoidable, close monitoring of toxicity is recommended. No a priori dose adjustment is recommended since the therapeutic index of imatinib is relatively high. Monitoring of imatinib plasma concentrations should be considered, if available. Note, no a priori dosage adjustment is recommended for imatinib with dermal administration of miconazole, since systemic exposure of miconazole is limited when used topically.

Coadministration has not been studied. Midazolam is metabolised by CYP3A4. Imatinib is a moderate inhibitor of CYP3A4 and may increase midazolam exposure. Close monitoring for toxicity is recommended.

Coadministration has not been studied. Midazolam is metabolised by CYP3A4. Imatinib is a moderate inhibitor of CYP3A4 and may increase midazolam exposure. Close 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%). Imatinib is unlikely to interfere with this pathways.

Coadministration has not been studied. Mirtazapine is metabolised to 8-hydroxymirtazapine by CYP2D6 and CYP1A2, and mainly through CYP3A4 to N-desmethylmirtazapine. Imatinib is a weak inhibitor of CYP2D6 and a moderate inhibitor of CYP3A4 and may increase mirtazapine concentrations. The clinical relevance of this interaction is unknown and close monitoring for toxicity is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Mometasone is metabolised by CYP3A4. Imatinib is a moderate inhibitor of CYP3A4 and may increase mometasone exposure. 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. Imatinib is a moderate inhibitor of CYP2C9 and CYP3A4 and may increase montelukast concentrations. The clinical relevance of this interaction is unknown and monitoring may be required.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Morphine is mainly glucuronidated to morphine-3-glucuronide (UGT2B7>UGT1A1) and, to a lesser extent, to the pharmacologically active morphine-6-glucuronide (UGT2B7>UGT1A1). Imatinib does not induce of inhibit UGTs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Moxifloxacin is predominantly glucuronidated by UGT1A1. Imatinib does not inhibit or induce UGTs.

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

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Naproxen is mainly glucuronidated by UGT2B7 (major) and demethylated to desmethylnaproxen by CYP2C9 (major) and CYP1A2. Imatinib is a moderate inhibitor of CYP2C9 and may increase naproxen concentrations. However, naproxen has a broad therapeutic index and a clinically relevant interaction is unlikely.

Coadministration has not been studied. Nateglinide is mainly metabolised by CYP2C9 (70%) and to a lesser extent by CYP3A4 (30%). Imatinib is a moderate inhibitor of CYP3A4 and CYP2C9 and may increase nateglinide concentrations. Close monitoring of blood glucose levels may be required.

Coadministration has not been studied. Nebivolol metabolism involves CYP2D6. Imatinib is a weak inhibitor of CYP2D6 and may increase nebivolol concentrations. The clinical relevance of this interaction is unknown. Monitoring of blood pressure is recommended.

Coadministration has not been studied and is not recommended. Nefazodone is metabolised mainly by CYP3A4 and is an inhibitor of CYP3A4. Nefazodone may increase imatinib concentrations due to inhibition of CYP3A4. Concurrent use of CYP3A4 inhibitors and imatinib should be avoided. Moreover, imatinib may increase nefazodone concentrations due to moderate inhibition of CYP3A4. If coadministration is unavoidable, close monitoring of toxicity is recommended. No a priori dose adjustment for imatinib is recommended since the therapeutic index of imatinib is relatively wide. Monitoring of imatinib plasma concentrations should be considered, if available.

Coadministration has not been studied. Nicardipine is metabolised mainly by CYP3A4 and to a lesser extent by CYPs 2D6 and 2C8. Imatinib is a moderate inhibitor of CYP3A4 and a weak inhibitor of CYP2D6 and may increase nicardipine concentrations. Nicardipine inhibits CYP3A4 and could potentially increase imatinib concentrations. The clinical relevance of these interactions is unknown. No a priori dosage adjustment is recommended for imatinib. Close monitoring of imatinib tolerability and monitoring of blood pressure is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nicotinamide is converted to N-methylnicotinamide by nicotinamide methyltransferase which in turn is metabolised by xanthine oxidase and aldehyde oxidase. Imatinib 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 imatinib exposure.

Coadministration has not been studied. Nifedipine is metabolised mainly by CYP3A4. Imatinib is a moderate inhibitor of CYP3A4 and may increase nifedipine concentrations. Close monitoring of blood pressure is recommended.

Coadministration has not been studied. Nimesulide is extensively metabolized in the liver following multiple pathways including CYP2C9. Imatinib is a moderate inhibitor of CYP2C9 and may increase nimesulide concentrations. The clinical relevance of this interaction is unknown. Monitoring for nimesulide toxicity may be required.

Coadministration has not been studied. Nisoldipine is metabolised by CYP3A4. Imatinib is a moderate inhibitor of CYP3A4 and may increase nisoldipine concentrations. Close monitoring of blood pressure is recommended.

Coadministration has not been studied. Nitrendipine is extensively metabolised mainly by CYP3A4. Imatinib is a moderate inhibitor of CYP3A4 and may increase nitrendipine concentrations. Close monitoring of blood pressure is recommended.

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%). Imatinib 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). Imatinib is a moderate inhibitor of CYP3A4 and may increase norelgestromin concentrations. However, since norelgestromin does not have a narrow therapeutic index, this is unlikely to be of clinical relevance.

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. Imatinib 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. Imatinib is a moderate inhibitor of CYP3A4 and CYP2C9 and a weak inhibitor of CYP2D6. However, since norgestimate does not have a narrow therapeutic index, this is unlikely to be of clinical relevance.

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. Imatinib is a moderate inhibitor of CYP3A4 and may increase levonorgestrel concentrations. However, since levonorgestrel does not have a narrow therapeutic index, this is unlikely to be of clinical relevance.

Coadministration has not been studied. Nortriptyline is metabolised mainly by CYP2D6. Imatinib is a weak inhibitor of CYP2D6 and may increase concentrations of nortriptyline. The clinical relevance of this interaction is unknown and monitoring may be required. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. 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 clinically significant interaction is unlikely. Ofloxacin is eliminated unchanged renally by glomerular filtration and active tubular secretion via both cationic and anionic transport systems. Imatinib is unlikely to interfere with this pathway. 

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). Imatinib 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. 

Imatinib is freely soluble up to a pH of 5.5 and no clinically significant effect of gastric pH increasing drugs on imatinib exposure is expected. Omeprazole is mainly metabolised by CYP2C19 and to a lesser extent by CYP3A4. Omeprazole induces CYP1A2 and inhibits CYP2C19. Imatinib is a moderate inhibitor of CYP3A4 and could increase omeprazole concentrations. However, coadministration of omeprazole (40 mg once daily) and imatinib (400 mg single dose) had no significant effect on imatinib AUC (7% increase) or Cmax (3% decrease) when coadministered to 12 healthy subjects.

Coadministration has not been studied. Ondansetron is metabolised mainly by CYP1A2 and CYP3A4 and to a lesser extent by CYP2D6, and is a substrate of P-gp. Imatinib is a moderate inhibitor of CYP3A4 and a weak inhibitor of CYP2D6 and may increase ondansetron concentrations. Monitoring for toxicity may be required. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Oxazepam is mainly glucuronidated. Imatinib does not induce or inhibit UGTs.

Coadministration should be avoided as significant decreases in imatinib plasma exposure may occur due to induction of CYP3A4. Mean trough concentrations of imatinib decreased by ~62% in patients on oxcarbazepine (n=6) when compared to patients not receiving antiepileptic drugs (n=111). Decreased imatinib exposure can lead to decreased efficacy. Inducers of CYP3A4 should be avoided, or selection of an alternate concomitant medicinal product, with no or minimal potential to induce CYP3A4 should be considered. If coadministration is necessary, the US product information recommends an imatinib dosage increase of at least 50% based on pharmacokinetic studies in combination with careful monitoring of clinical response. Monitoring of imatinib plasma concentrations should be considered, if available.

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

Coadministration has not been studied. Oxycodone is metabolised principally to noroxycodone via CYP3A and oxymorphone via CYP2D6. Imatinib is a moderate inhibitor of CYP3A4 and a weak inhibitor of CYP2D6 and may increase oxycodone concentrations. Close monitoring for oxycodone toxicity is recommended when imatinib and oxycodone are coadministered.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Paliperidone is primarily eliminated renally (possibly via OCT) with minimal metabolism occurring via CYPs 2D6 and 3A4. Imatinib is a moderate inhibitor of CYP3A4 and a weak inhibitor of CYP2D6 and may increase paliperidone concentrations. However, since these are minor pathways, this is unlikely to be of clinical relevance.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Palonosetron is metabolised mainly by CYP3A4 and to a lesser extent by CYP2D6 and CYP1A2, and is a substrate of P-gp. Imatinib is a moderate inhibitor of CYP3A4 and a weak inhibitor of CYP2D6 and may increase palonosetron concentrations. Monitoring for toxicity may be required. 

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 but based on metabolism and clearance a clinically significant interaction is unlikely. Imatinib is freely soluble up to a pH of 5.5 and no clinically significant effect of gastric pH increasing drugs on imatinib exposure is expected. Pantoprazole is mainly metabolised by CYP2C19 and to a lesser extent by CYPs 3A4, 2D6 and 2C9. Imatinib is a moderate inhibitor of CYP3A4 and a weak inhibitor of CYP2D6 and may increase pantoprazole concentrations. However, since these are minor pathways and pantoprazole 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. Para-aminosalicylic acid and its acetylated metabolite are mainly excreted in the urine by glomerular filtration and tubular secretion. Imatinib does not interact with this metabolic pathway. 

Coadministration of paracetamol (1000 mg single dose) and imatinib (400 mg daily) was studied in 12 Korean patients with chronic myelogenous leukaemia. There was no significant effect on pharmacokinetics of paracetamol or its glucuronide and sulphate metabolites. There was no evidence of an effect of a single dose of paracetamol on the pharmacokinetics of imatinib. Imatinib can be safely administered with paracetamol without dose adjustment of either drug. Paracetamol is mainly metabolized by glucuronidation (via UGT1A9 (major), UGT1A6, UGT1A1, UGT2B15) and sulfation and, to a lesser extent, by oxidation (CYP2E1 (major), 1A2, 3A4 and 2D6). There is no evidence that imatinib inhibits or induces UGT1A9 and CYP2E1.

Coadministration has not been studied. Paroxetine is mainly metabolised by CYP2D6 and CYP3A4. Imatinib is a weak inhibitor of CYP2D6 and a moderate inhibitor of CYP3A4 and may increase paroxetine concentrations. The clinical relevance of this interaction is unknown and close monitoring for toxicity is recommended.

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

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). Imatinib 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 oxidated via FMO3. Imatinib is a moderate inhibitor of CYP3A4 and may increase perazine concentrations. Close monitoring is recommended.

Coadministration has not been studied. The metabolism of periciazine has not been well characterized but is likely to involve CYP2D6. Imatinib is a weak inhibitor of CYP2D6 and may increase periciazine concentrations. The clinical relevance of this interaction is unknown and 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 the urine. Imatinib is a moderate inhibitor of CYP3A4 and may decrease biotransformation to active substance. The clinical relevance of this interaction is unknown and close monitoring of blood pressure is recommended. 

Coadministration has not been studied. Perphenazine is metabolised by CYP2D6. Imatinib is a weak inhibitor of CYP2D6 and may increase perphenazine concentrations. The clinical relevance of this interaction is unknown and monitoring may be required. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pethidine is metabolised mainly by CYP2B6 and to a lesser extent by CYP3A4. Imatinib is a moderate inhibitor of CYP3A4; however, since CYP3A4 mediated metabolism is a minor pathway, this is unlikely to be of clinical relevance.

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. Imatinib does not interact with phenelzine metabolic pathway.

Coadministration should be avoided as significant decreases in imatinib plasma exposure may occur due to induction of CYP3A4 by phenobarbital. Decreased imatinib exposure can lead to decreased efficacy. Inducers of CYP3A4 should be avoided, or selection of an alternate concomitant medicinal product, with no or minimal potential to induce CYP3A4 should be considered. If coadministration is necessary, the US product information recommends an imatinib dosage increase of at least 50% based on pharmacokinetic studies in combination with careful monitoring of clinical response. Monitoring of imatinib plasma concentrations should be considered, if available.

Coadministration has not been studied but is contraindicated. Phenprocoumon is metabolised by CYP2C9 and CYP3A4. Imatinib is a moderate inhibitor of CYP2C9 and CYP3A4, and may increase concentrations of phenprocoumon. Due to known increased risks of bleeding in conjunction with the use of imatinib (e.g. haemorrhage), patients who require anticoagulation should receive low-molecular-weight or standard heparin, instead of coumarin derivatives.

Coadministration has not been studied but should be avoided. Phenytoin is mainly metabolised by CYP2C9 and to a lesser extent by CYP2C19. Imatinib is a moderate inhibitor of CYP2C9 and may increase concentrations of phenytoin. Close monitoring for phenytoin toxicity is recommended. Furthermore, phenytoin is a potent inducer of CYP3A4, UGT and P-gp. Concentrations of imatinib may decrease due to induction of CYP3A4. Mean trough concentrations of imatinib decreased by ~73% in patients on phenytoin (n=15) when compared to patients not receiving antiepileptic drugs (n=111). In one patient within a clinical study, the AUC of a 350 mg dose of imatinib in combination with phenytoin was comparable to a dose of 85 mg imatinib monotherapy. A decrease in exposure can lead to decreased efficacy. Therefore, coadministration should be avoided. Selection of an alternate concomitant medicinal product, with no or minimal potential to induce CYP3A4 should be considered. If coadministration is necessary, the US product label recommends an imatinib dosage increase of at least 50% based on pharmacokinetic studies in combination with careful monitoring of clinical response. Monitoring of imatinib plasma concentrations should be considered, 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. Imatinib does not interact with this metabolic pathway. 

Coadministration has not been studied. Pimozide is mainly metabolised by CYP3A4. Imatinib is a moderate inhibitor of CYP3A4 and may increase pimozide concentrations. The clinical relevance of this interaction is unknown and close monitoring for pimozide toxicity is recommended.

Coadministration has not been studied. Pindolol is partly metabolised to hydroxymetabolites (possibly via CYP2D6) and partly eliminated unchanged in the urine. Imatinib is a weak inhibitor of CYP2D6 and may increase pindolol concentrations. 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. Pioglitazone is metabolised mainly by CYP2C8 and to a lesser extent by CYPs 3A4, 1A2 and 2C9. Imatinib is a moderate inhibitor of CYP3A4 and CYP2C9 and may increase pioglitazone concentrations. However since CYP3A4 and CYP2C9 mediated metabolism are minor pathways, this is unlikely to be of clinical relevance.

Coadministration has not been studied. The metabolism of pipotiazine has not been well described but may involve CYP2D6. Imatinib is a weak inhibitor of CYP2D6 and may increase pipotiazine concentrations. The clinical relevance of this interaction is unknown and monitoring may be required. 

Coadministration has not been studied. Piroxicam is primarily metabolised by CYP2C9. Imatinib is a moderate inhibitor of CYP2C9 and may increase concentrations of piroxicam. Close monitoring for piroxicam toxicity is recommended.

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. Imatinib is a moderate inhibitor of CYP2C9, however, since CYP2C9 is only a minor pathway, a clinically relevant interaction is unlikely.

Coadministration has not been studied and is not recommended as imatinib concentrations may increase due to inhibition of CYP3A4 by posaconazole. Concurrent use of CYP3A4 inhibitors should be avoided. If coadministration is unavoidable, close monitoring of toxicity is recommended. No a priori dose adjustment is recommended since the therapeutic index of imatinib is relatively high. Monitoring of imatinib plasma concentrations should 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. Concentrations of the active metabolite may decrease due to moderate inhibition of CYP3A4 by imatinib. Selection of an alternate concomitant medicinal product, with no or minimal potential to interact with the formation of active metabolite should be considered.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Prazosin is extensively metabolised, primarily by demethylation and conjugation. Imatinib 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. Imatinib is a moderate inhibitor of CYP3A4 and may increase prednisolone exposure. However, since prednisolone has a broad 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. Imatinib is a moderate inhibitor of CYP3A4 and may increase prednisolone exposure. However, since prednisone 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. Prochlorperazine is metabolised by CYP2D6 and CYP2C19. Imatinib is a weak inhibitor of CYP2D6 and may increase prochlorperazine concentrations. The clinical relevance of this interaction is unknown. 

Coadministration has not been studied. Promethazine is metabolised by CYP2D6. Imatinib is a weak inhibitor of CYP2D6 and may increase promethazine concentrations. The clinical relevance of this interaction is unknown.

Coadministration has not been studied. Propafenone is metabolised mainly by CYP2D6 and to a lesser extent CYP1A2 and CYP3A4. Imatinib is a weak inhibitor of CYP2D6 and a moderate inhibitor of CYP3A4 and may increase propafenone concentrations. Monitoring for propafenone toxicity may be required.

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). Imatinib is a weak inhibitor of CYP2D6 and may increase propranolol concentrations. 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. Prucalopride is minimally metabolised and mainly eliminated renally, partly by active secretion by renal transporters. Prucalopride is a substrate of P-gp, but 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. Imatinib 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. Imatinib is a moderate inhibitor of CYP3A4 and may increase quetiapine concentrations. The clinical relevance of this interaction is unknown and close monitoring for quetiapine toxicity is recommended.

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. Imatinib does not impact this renal transporter. 

Coadministration has not been studied. Quinidine is a substrate for CYP3A4 and is an inhibitor of CYP2D6. Imatinib is a moderate inhibitor of CYP3A4. As quinidine has a small therapeutic index, close monitoring for quinidine toxicity is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Imatinib is freely soluble up to a pH of 5.5 and no clinically significant effect of gastric pH increasing drugs on imatinib exposure is expected. Rabeprazole is mainly metabolised via non-enzymatic reduction and to a lesser extent by CYPs 2C19 and 3A4. Imatinib is a moderate inhibitor of CYP3A4 and may increase rabeprazole concentrations. However, since CYP3A4 mediated metabolism is a minor pathway and rabeprazole has a wide therapeutic index, a clinically relevant interaction is unlikely.

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. Imatinib is a moderate inhibitor of CYP3A4 and may decrease biotransformation to active substance. The clinical relevance of this interaction is unknown and close monitoring of blood pressure is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Imatinib is freely soluble up to a pH of 5.5 and no clinically significant effect of gastric pH increasing drugs on imatinib exposure is expected.

Coadministration has not been studied. Ranolazine is primarily metabolised by CYP3A4 and to a lesser extent by CYP2D6. Ranolazine is also a substrate of P-gp. Imatinib is an inhibitor of CYP3A4 (moderate) and CYP2D6 (weak), and may increase ranolazine concentrations. Close monitoring of blood pressure is recommended. No a priori dosage adjustment for imatinib and ranolazine is recommended. Furthermore, ranolazine is a weak inhibitor of P-gp, CYP3A4 and CYP2D6 and may increase concentrations of imatinib. However, due to the relatively high therapeutic index of imatinib, no clinically significant effect on imatinib is expected.

Coadministration has not been studied. Reboxetine is metabolised by CYP3A4. Imatinib is a moderate inhibitor of CYP3A4 and may increase reboxetine concentrations. The clinical relevance of this interaction is unknown and close monitoring for toxicity is recommended. In vitro data indicate reboxetine to be a weak inhibitor of CYP3A4 but in vivo data showed no inhibitory effect on CYP3A4. 

Coadministration has not been studied. Repaglinide is metabolised by CYPs 2C8 and 3A4 and clinical data seem to indicate that it is a substrate of the hepatic transporter OATP1B1. Imatinib is a moderate inhibitor of CYP3A4 and may increase repaglinide concentrations. Close monitoring of blood glucose levels 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. Imatinib does not interact with this metabolic pathway. 

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

Coadministration has not been studied but should be avoided as significant decreases in imatinib plasma concentrations may occur due to induction of CYP3A4. Decreases in imatinib exposure can lead to decreased efficacy. Inducers of CYP3A4 should be avoided, or selection of an alternate concomitant medicinal product, with no or minimal potential to induce CYP3A4 should be considered. If coadministration is necessary, the US Prescribing Information for imatanib recommends an imatinib dosage increase of at least 50% based on pharmacokinetic studies in combination with careful monitoring of clinical response. Monitoring of imatinib plasma concentrations should be considered, if available.

Coadministration should be avoided as significant decreases in imatinib plasma concentrations may occur due to induction of CYP3A4. Coadministration of rifampicin and imatinib decreased imatinib Cmax and AUC by at least 54% and 75%, respectively. Decreases in imatinib exposure can lead to decreased efficacy. Inducers of CYP3A4 should be avoided, or selection of an alternate concomitant medicinal product, with no or minimal potential to induce CYP3A4 should be considered. If coadministration is necessary, the US Prescribing Information for imatinib recommends an imatinib dosage increase of at least 50% based on pharmacokinetic studies in combination with careful monitoring of clinical response. Monitoring of imatinib plasma concentrations should be considered, if available.

Coadministration has not been studied but should be avoided as significant decreases in imatinib plasma concentrations may occur due to induction of CYP3A4. Decreases in imatinib exposure can lead to decreased efficacy. Inducers of CYP3A4 should be avoided, or selection of an alternate concomitant medicinal product, with no or minimal potential to induce CYP3A4 should be considered. If coadministration is necessary, the US Prescribing Information for imatinib recommends an imatinib dosage increase of at least 50% based on pharmacokinetic studies in combination with careful monitoring of clinical response. Monitoring of imatinib plasma concentrations should be considered, if available.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Rifaximin is mainly excreted in faeces, almost entirely as unchanged drug. Imatinib 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. Imatinib is a weak inhibitor of CYP2D6 and a moderate inhibitor of CYP3A4 and may increase risperidone concentrations. The clinical relevance of this interaction is unknown and monitoring may be required. 

Coadministration has not been studied. Rivaroxaban is partly metabolised in the liver (by CYP3A4, CYP2J2 and hydrolytic enzymes) and partly eliminated unchanged in urine (by P-gp and BCRP). Concentrations of rivaroxaban may increase due to moderate inhibition of CYP3A4 by imatinib. Close monitoring of anti-Xa levels is recommended if coadministered.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Rosiglitazone is metabolised mainly by CYP2C8 and to a lesser extent by CYP2C9. Imatinib is a moderate inhibitor of CYP2C9 and may increase pioglitazone concentrations. However since CYP2C9 mediated metabolism is a minor pathway, this is unlikely to be of clinical relevance.

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

Coadministration has not been studied. Salmeterol is metabolised by CYP3A4. Imatinib is a moderate inhibitor of CYP3A4. Although, the systemic absorption of salmeterol after bronchial administration is low, increased systemic exposure to salmeterol may occur. The clinical relevance of this interaction is unknown. Monitoring for toxicity is recommended.

Coadministration has not been studied. Saxagliptin is mainly metabolised by CYP3A4 and is a substrate of P-gp. Imatinib is a moderate inhibitor of CYP3A4 and may increase repaglinide concentrations. Close monitoring of blood glucose levels may be required.

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

Coadministration has not been studied. Sertindole is metabolised by CYP2D6 and CYP3A4. Imatinib is a weak inhibitor of CYP2D6 and as moderate inhibitor of CYP3A4 and may increase sertindole concentrations. The clinical relevance of this interaction is unknown and close monitoring for sertindole toxicity is recommended.

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. Imatinib is a moderate inhibitor of CYP3A4 and a weak inhibitor of CYP2D6, however since CYP3A4 and CYP2D6 mediated metabolism are minor pathways, this is unlikely to be of clinical relevance.

Sildenafil is metabolised mainly by CYP3A4 and to a lesser extent by CYP2C9. Imatinib is a moderate inhibitor of CYP3A4 and CYP2C9 and may increase sildenafil exposure. Population pharmacokinetics of imatinib and sildenafil were determined in a phase III study in patients with pulmonary arterial hypertension receiving imatinib (n=69) or placebo (n=81). Coadministration was estimated to have no effect on imatinib concentrations and to increase sildenafil concentrations by ~64%. Close monitoring of sildenafil tolerability is recommended.

Simvastatin is metabolised by CYP3A4 and the metabolite is a substrate of OATP1B1. Imatinib is a moderate inhibitor of CYP3A4 and may increase simvastatin concentrations. Coadministration of imatinib (400 mg once daily) and simvastatin (40 mg single dose) increased simvastatin Cmax and AUC by 2.0- and 3.5-fold (n=20). Alternatives to simvastatin, i.e. pravastatin or rosuvastatin, should be considered.

Coadministration has not been studied. Sirolimus is metabolised by CYP3A4 and is a substrate of P-gp. Imatinib is a moderate inhibitor of CYP3A4 and may increase sirolimus concentrations. 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, P-gp) and metabolism by CYP3A4 represents a minor elimination pathway. Imatinib is an inhibitor of CYP3A4 and may increase sitagliptin concentrations. However since CYP3A4 mediated metabolism is a minor pathway, this is unlikely to be of clinical relevance.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Sodium nitroprusside is rapidly metabolised, likely by interaction with sulfhydryl groups in the erythrocytes and tissues. Cyanogen (cyanide radical) is produced which is converted to thiocyanate in the liver by the enzyme thiosulfate sulfurtransferase. There is little potential for sodium nitroprusside to affect the disposition of imatinib, or to be affected if co-administered with imatinib. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as sotalol is excreted unchanged via renal elimination. 

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. Imatinib 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. Imatinib does not affect this metabolic pathway. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Stanozolol undergoes hepatic metabolism. Imatinib is a moderate inhibitor of CYP3A4 and CYP2C9. Imatinib is a moderate inhibitor of CYP2C9 and may increase stanozolol exposure. However, since stanozolol has a wide therapeutic index, a clinically relevant interaction is unlikely.

Coadministration should be avoided. St John’s wort may cause significant and unpredictable decreases in the plasma concentrations of imatinib due to induction of CYP3A4 and P-gp. Coadministration of St John’s wort (300 mg three times daily) and imatinib (400 mg single dose) was assessed in two studies in healthy subjects. In one study imatinib AUC and Cmax decreased by 32% and 29% (n=10) and in the other AUC and Cmax decreased by 30% and 15% (n=12). 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Like other proteins, streptokinase is metabolised proteolytically in the liver and eliminated via the kidneys. Streptokinase is unlikely to affect the disposition of tyrosine kinase inhibitors, or to be affected if coadministered with tyrosine kinase inhibitors.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. In vitro studies suggest a role of CYP2C9 in sulfadiazine metabolism. Concentrations of sulfadiazine may increase due to moderate inhibition of CYP2C9 by imatinib. Close monitoring for sulfadiazine toxicity is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Sulpiride is mainly excreted in the urine and faeces as unchanged drug. 

Coadministration has not been studied. Tacrolimus is metabolised by CYP3A4 and inhibits CYP3A4 and OATP1B1 in vitro, but produced modest inhibition of CYP3A4 and OATP1B1 in the range of clinical concentrations. Imatinib is a moderate inhibitor of CYP3A4 and may slightly increase tacrolimus concentrations. Imatinib is metabolised mainly by CYP3A4 and concentrations may increase due to inhibition of CYP3A4 by tacrolimus, although to a modest extent. No a priori dosage adjustment of imatinib and tacrolimus 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. Imatinib is a moderate inhibitor of CYP3A4 and may increase tadalafil exposure. Close monitoring of tadalafil tolerability is recommended.

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. Imatinib is a moderate inhibitor of CYP3A4 and a weak inhibitor of CYP2D6 and may increase concentrations of tamsulosin. 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. Imatinib does not interact with this elimination pathway.

Coadministration has not been studied but may increase imatinib concentrations due to inhibition of CYP3A4 by telithromycin. Concurrent use of CYP3A4 inhibitors should be avoided. If coadministration is unavoidable, close monitoring of toxicity is recommended. No a priori dose adjustment is recommended since the therapeutic index of imatinib is relatively wide. Monitoring of imatinib plasma concentrations should be considered, if available. 

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Temazepam is mainly glucuronidated. Imatinib does not induce or inhibit UGTs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Terbinafine is metabolised by CYPs 1A2, 2C9, 3A4 and to a lesser extent by CYPs 2C8 and 2C19. Terbinafine inhibits CYP2D6 and imatinib is a moderate inhibitor of CYPs 3A4 and 2C9. However since these are minor pathways in the metabolism of imatinib and terbinafine, this is unlikely to be of clinical relevance.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Testosterone is metabolised by CYP3A4. Imatinib is a moderate inhibitor of CYP3A4. Imatinib is a moderate inhibitor of CYP3A4 and may increase testosterone exposure. 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.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Theophylline is mainly metabolised by CYP1A2. Imatinib 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. Thioridazine is metabolised by CYP2D6 and to a lesser extent by CYP3A4. Imatinib is a weak inhibitor of CYP2D6 and a moderate inhibitor of CYP3A4 and may increase concentrations of thioridazine. The clinical relevance of this interaction is unknown and monitoring may be required.

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

Coadministration has not been studied. Ticagrelor undergoes extensive CYP3A4 metabolism and is only a mild inhibitor of CYP3A4. Imatinib concentrations may be slightly increased if co-administered with ticagrelor but this is not expected to be clinically relevant. However, concentrations of ticagrelor may increase due to moderate inhibition of CYP3A4 by imatinib. Selection of an alternate concomitant medicinal product, with no or minimal potential to interact with CYP3A4 should be considered.

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. Imatinib is a weak inhibitor of CYP2D6 and may increase timolol concentrations. However, the systemic absorption of timolol after ocular administration is low and 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. Imatinib 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. Imatinib is a moderate inhibitor of CYP2C9 and may increase tolbutamide concentrations. Close monitoring of blood glucose levels may be required.