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. Dabrafenib is unlikely to interfere with this pathway. 

Coadministration has not been studied. Acenocoumarol is mainly metabolised by CYP2C9 and to a lesser extent by CYP1A2 and CYP2C19. Dabrafenib is an inducer of CYP2C9 and is a potential inducer of CYP2C19. Concentrations of acenocoumarol may decrease due to induction of CYP2C9. Monitoring of INR is recommended. 

Coadministration has not been studied. Aspirin is rapidly deacetylated to form salicylic acid and then further metabolised by glucuronidation (by several UGTs, major UGT1A6). Dabrafenib is a potential inducer of UGT and may decrease concentrations of aspirin. Monitoring of aspirin efficacy is recommended. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Agomelatine is metabolised predominantly via CYP1A2 (90%), with a small proportion metabolised by CYP2C9 and CYP2C19 (10%). Dabrafenib is an inducer of CYP2C9 and potentially induces CYP2C19. Since CYP2C9 and CYP2C19 mediated metabolism is only a minor pathway, a clinically relevant interaction is unlikely.

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

Coadministration has not been studied. Alfentanil undergoes extensive CYP3A4 metabolism. Dabrafenib is a strong CYP3A4 inducer and may decrease concentrations of alfentanil. Monitoring of alfentanil efficacy is recommended. 

Coadministration has not been studied. Alfuzosin is metabolised by CYP3A. Dabrafenib is an inducer of CYP3A4 and may decrease alfuzosin concentrations. Although, alfuzosin has a wide therapeutic index, monitoring of alfuzosin efficacy may be required.

Coadministration has not been studied. Aliskiren is minimally metabolised and is mainly excreted unchanged in faeces. P-gp is a major determinant of aliskiren bioavailability. Dabrafenib is an inducer of P-gp but a clinically relevant interaction is unlikely.

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

Coadministration has not been studied. In vitro data indicate that alosetron is metabolised by CYPs 2C9, 3A4 and 1A2. Dabrafenib is an inducer of CYP3A4 and CYP2C9, and may decrease concentrations of alosetron. Monitoring of alosetron efficacy is recommended. 

Coadministration has not been studied. Alprazolam is mainly metabolised by CYP3A4. Dabrafenib is an inducer of CYP3A4 and may decrease alprazolam concentrations. Consider monitoring of alprazolam efficacy.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. The aqueous solubility of dabrafenib is pH dependent with only a low solubility at pH 1. Coadministration of dabrafenib (150 mg twice daily) and rabeprazole (40 mg once daily) increased dabrafenib AUC by 3% and decreased dabrafenib Cmax by 12%. Therefore, no clinically relevant effect of aluminium hydroxide on dabrafenib exposure is expected.

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. Dabrafenib is an inducer of CYP3A4 and possibly of UGTs and CYP2C19. Therefore, dabrafenib may decrease the plasma concentration of ambrisentan. Monitoring of ambrisentan efficacy may be required. Furthermore, ambrisentan is also a substrate of P-gp. Although, dabrafenib is an inducer of P-gp, the risk of a clinically relevant interaction through P-gp is minimal.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amikacin is eliminated by glomerular filtration. Dabrafenib does not interfere with this elimination pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amiloride is eliminated unchanged in the kidney. In vitro data indicate that amiloride is a substrate of OCT2. Dabrafenib is unlikely to interfere with this elimination pathway.

Coadministration has not been studied but should be approached with caution. Amiodarone is metabolised by CYP2C8 and CYP3A4. Dabrafenib is an inducer of CYP3A4 and potentially induces CYP2C8, and may decrease concentrations of amiodarone. Due to the narrow therapeutic index of amiodarone, dose increments should be considered and monitoring of amiodarone efficacy is recommended. Monitoring of amiodarone plasma concentrations should be considered, if available. Moreover, the major metabolite of amiodarone, desethylamiodarone, is an inhibitor of CYP3A4 (weak), CYP2C9 (moderate), CYP2D6 (moderate), CYP2C19 (weak), CYP1A1 (strong), CYP2B6 (moderate) and P-gp (strong). This does not affect dabrafenib. No clinically relevant QTc prolonging effects were observed after administration of 300 mg dabrafenib twice daily (two times the recommended dose). However, the incidences of QTc ≥501 msec and of QTc increase of > 60 msec from baseline were significantly higher with the combination dabrafenib-trametinib (4% and 13%, respectively) compared with the trametinib (2% and 3%, respectively) and the dabrafenib (<1% and 3%, respectively) monotherapy populations. Therefore, caution is needed when trametinib and dabrafenib are used concomitantly and are co-administered with a drug with a known risk of Torsade de Pointes. If coadministration is necessary, close monitoring including ECG assessment is recommended. Note: due to the long half-life of amiodarone, interactions can be observed for several months after discontinuation of amiodarone.

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

Coadministration has not been studied. Amitriptyline and its active metabolite nortriptyline are metabolised predominantly by CYPs 3A4, 2D6 and 2C19. Dabrafenib is an inducer of CYP3A4 and is a potential inducer of CYP2C19. Concentrations of amitriptyline may decrease but concentrations of nortriptyline may increase due to induction of CYP3A4. Monitoring for amitriptyline/nortriptyline efficacy and plasma concentrations is recommended. No clinically relevant QTc prolonging effects were observed after administration of dabrafenib (300 mg twice daily, two times the recommended dose). However, the incidences of QTc ≥501 msec and QTc increase of >60 msec from baseline were significantly higher with the combination dabrafenib-trametinib (4% and 13%, respectively) compared with trametinib (2% and 3%, respectively) and dabrafenib (<1% and 3%, respectively) monotherapies. Therefore, caution is needed when trametinib and dabrafenib are used concomitantly and are co-administered with a drug with a known risk of Torsade de Pointes. If coadministration with amitriptyline is necessary, close monitoring including ECG assessment is recommended.

Coadministration has not been studied. Amlodipine is metabolised by CYP3A4. Dabrafenib is an inducer of CYP3A4 and may decrease amlodipine concentrations. As the clinical relevance of this interaction is unknown, monitoring of blood pressure is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amoxicillin is mainly excreted in the urine by glomerular filtration and tubular secretion. In vitro data indicate that amoxicillin is a substrate of OAT3. Dabrafenib is an inhibitor of OAT3 in vitro, but a clinically relevant interaction is unlikely.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Amphotericin B is not appreciably metabolised and is eliminated to a large extent in the bile. Dabrafenib does not interfere with this metabolic or elimination pathway. However, the European SPC for amphotericin states that concomitant use of amphotericin B and antineoplastic agents can increase the risk of renal toxicity, bronchospasm and hypotension. No clinically relevant QTc prolonging effects were observed after administration of dabrafenib (300 mg twice daily, two times the recommended dose). However, the incidences of QTc ≥501 msec and QTc increase of >60 msec from baseline were significantly higher with the combination dabrafenib-trametinib (4% and 13%, respectively) compared with trametinib (2% and 3%, respectively) and dabrafenib (<1% and 3%, respectively) monotherapies. Therefore, caution is needed when trametinib and dabrafenib are used concomitantly and are co-administered with a drug with a known risk of Torsade de Pointes. If coadministration with amphotericin B is necessary, close monitoring including ECG assessment is recommended.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Anidulafungin is not metabolised hepatically but undergoes chemical degradation at physiological temperatures. Dabrafenib does not interfere with this pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. The aqueous solubility of dabrafenib is pH dependent with only a low solubility at pH 1. Coadministration of dabrafenib (150 mg twice daily) and rabeprazole (40 mg once daily) increased dabrafenib AUC by 3% and decreased dabrafenib Cmax by 12%. Therefore, no clinically relevant effect of antacids on dabrafenib exposure is expected.

Coadministration has not been studied. Apixaban is metabolised by CYP3A4 and to a lesser extent by CYPs 1A2, 2C8, 2C9 and 2C19. Dabrafenib is an inducer of CYP3A4, CYP2C9 and is a potential inducer of CYP2C8 and CYP2C19. Concentrations of apixaban may decrease due to induction of CYP3A4 and CYP2C9. Therefore, coadministration is not recommended. If coadministration is necessary, monitoring of apixaban efficacy is recommended and close monitoring for anti-Xa levels should be considered, if available.

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. Dabrafenib is an inducer of CYP3A4 and possibly of CYP2C19, and may decrease concentrations of aprepitant. Dose increments for aprepitant should be considered and monitoring of aprepitant efficacy may be required. Furthermore, during treatment aprepitant is a moderate inhibitor of CYP3A4 and may increase concentrations of dabrafenib during the three days of coadministration. Therefore, coadministration is not recommended. If coadministration is unavoidable, monitor closely for dabrafenib toxicity during the few days of coadministration and reduce the dabrafenib dose by 50%. After treatment, aprepitant is a weak inducer of CYP3A4, CYP2C9 and UGT. Concentrations of dabrafenib 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. Dabrafenib is an inducer of CYP3A4 and may decrease aripiprazole concentrations. Monitoring of aripiprazole efficacy is recommended.

Coadministration has not been studied. Asenapine is metabolised by glucuronidation (UGT1A4) and oxidative metabolism (CYPs 1A2 (major), 3A4 and 2D6 (minor)). Dabrafenib is an inducer of CYP3A4 and is a potential inducer of UGT. Concentrations of asenapine may decrease due to induction of CYP3A4. As the clinical relevance of this interaction is unknown, monitoring of asenapine efficacy may be required.

Coadministration has not been studied. Astemizole is metabolised by CYPs 2D6, 2J2 and 3A4. Dabrafenib is an inducer of CYP3A4 and may decrease concentrations of astemizole. The clinical relevance of this interaction is unknown and monitoring of astemizole efficacy may be necessary. No clinically relevant QTc prolonging effects were observed after administration of dabrafenib (300 mg twice daily, two times the recommended dose). However, the incidences of QTc ≥501 msec and QTc increase of >60 msec from baseline were significantly higher with the combination dabrafenib-trametinib (4% and 13%, respectively) compared with trametinib (2% and 3%, respectively) and dabrafenib (<1% and 3%, respectively) monotherapies. Therefore, caution is needed when trametinib and dabrafenib are used concomitantly and are co-administered with a drug with a known risk of Torsade de Pointes. If coadministration with astemizole is necessary, close monitoring including ECG assessment is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Atenolol is mainly eliminated unchanged in the kidney, predominantly by glomerular filtration. Dabrafenib does not interfere with this elimination pathway.

Coadministration has not been studied. Atorvastatin is metabolised by CYP3A4 and is a substrate of P-gp and OATP1B1. Dabrafenib is an inducer of CYP3A4 and P-gp, and an inhibitor of OATP1B1. The risk of a clinically significant interaction due to OATP1B1 inhibition is unlikely. However, dabrafenib may decrease atorvastatin concentrations due to induction of CYP3A4 and P-gp. Monitoring of cholesterol concentrations is recommended and adjust dose accordingly.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Azathioprine is converted to 6-mercaptopurine which is metabolised analogously to natural purines. Dabrafenib does not interfere with this metabolic pathway. However, coadministration may increase risk of neutropenia, fatigue, and thrombocytopenia. Due to the risk of additive haematological toxicity, haematological parameters should be monitored if coadministered with trametinib plus dabrafenib.

Coadministration has not been studied but should be approached with caution. Azithromycin is mainly eliminated via biliary excretion with animal data suggesting this may occur via P-gp and MRP2. Dabrafenib is an inducer of P-gp, but this is unlikely to be clinically relevant. No clinically relevant QTc prolonging effects were observed after administration of dabrafenib (300 mg twice daily, two times the recommended dose). However, the incidences of QTc ≥501 msec and QTc increase of >60 msec from baseline were significantly higher with the combination dabrafenib-trametinib (4% and 13%, respectively) compared with trametinib (2% and 3%, respectively) and dabrafenib (<1% and 3%, respectively) monotherapies. Therefore, caution is needed when trametinib and dabrafenib are used concomitantly and are co-administered with a drug with a known risk of Torsade de Pointes. If coadministration with azithromycin is necessary, close monitoring including ECG assessment is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Beclometasone is a pro-drug which is not metabolised by CYP450, but is hydrolysed via esterase enzymes to the highly active metabolite beclometasone-17-monopropionate. Dabrafenib does not interact with this metabolic pathway. 

Coadministration has not been studied but should be approached with caution. Bedaquiline is metabolised by CYP3A4. Dabrafenib is a strong inducer of CYP3A4 and may decrease concentrations of bedaquiline. Due to the narrow therapeutic index of bedaquiline dose increments should be considered and monitoring of bedaquiline efficacy is recommended. No clinically relevant QTc prolonging effects were observed after administration of dabrafenib (300 mg twice daily, two times the recommended dose). However, the incidences of QTc ≥501 msec and QTc increase of >60 msec from baseline were significantly higher with the combination dabrafenib-trametinib (4% and 13%, respectively) compared with trametinib (2% and 3%, respectively) and dabrafenib (<1% and 3%, respectively) monotherapies. Therefore, caution is needed when trametinib and dabrafenib are used concomitantly and are co-administered with a drug with a known risk of Torsade de Pointes. If coadministration with bedaquiline is necessary, close monitoring including ECG assessment is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bendroflumethiazide is mainly eliminated by hepatic metabolism (70%) and excreted unchanged in the urine (30%) via OAT1 and OAT3. In vitro data indicate that bendroflumethiazide inhibits these renal transporters but a clinically relevant drug interaction is unlikely in the range of observed clinical concentrations. Dabrafenib is also an inhibitor of OAT1 and OAT3 in vitro but a clinically relevant interaction is unlikely.

Coadministration has not been studied. Bepridil is metabolised by CYP2D6 (major) and CYP3A4. Dabrafenib is an inducer of CYP3A4 and may decrease concentrations of bepridil. Since CYP3A4 mediated metabolism is a minor pathway, this is unlikely to be clinically significant but monitoring of bepridil efficacy may be required. No clinically relevant QTc prolonging effects were observed after administration of dabrafenib (300 mg twice daily, two times the recommended dose). However, the incidences of QTc ≥501 msec and QTc increase of >60 msec from baseline were significantly higher with the combination dabrafenib-trametinib (4% and 13%, respectively) compared with trametinib (2% and 3%, respectively) and dabrafenib (<1% and 3%, respectively) monotherapies. Therefore, caution is needed when trametinib and dabrafenib are used concomitantly and are co-administered with a drug with a known risk of Torsade de Pointes. If coadministration with bepridil is necessary, close monitoring including ECG assessment is recommended.

Coadministration has not been studied. Betamethasone is metabolised by CYP3A4. Dabrafenib is an inducer of CYP3A4 and may decrease betamethasone concentrations. Since betamethasone has a wide therapeutic index, this is unlikely to be of clinical significance but monitoring of efficacy may be required.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Half of a bezafibrate dose is eliminated unchanged in the urine. In vitro data suggest that bezafibrate inhibits the renal transporter OAT1. Dabrafenib does not interact with this pathway.

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

Coadministration has not been studied. Bisoprolol is partly metabolised by CYP3A4 and CYP2D6, and partly eliminated unchanged in the urine. Dabrafenib is an inducer of CYP3A4 and may decrease bisoprolol concentrations. As the clinical relevance of this interaction is unknown, monitoring of blood pressure and heart rate is recommended.

Coadministration has not been studied. Bosentan is a substrate and inducer of CYP3A4 and CYP2C9, and may decrease concentrations of dabrafenib. Dabrafenib is also an inducer of CYP3A4 and CYP2C9, and may decrease concentrations of bosentan. If coadministration is necessary, close monitoring of dabrafenib efficacy and bosentan efficacy is required. 

Coadministration has not been studied. Bromazepam undergoes oxidative biotransformation. Interaction studies indicate that CYP3A4 plays a minor role in bromazepam metabolism, but other cytochromes such as CYP2D6 or CYP1A2 may play a role. Dabrafenib is an inducer of CYP3A4 and may decrease bromazepam concentrations. Consider monitoring of bromazepam efficacy.

Coadministration has not been studied. Budesonide is metabolised by CYP3A4. Dabrafenib is an inducer of CYP3A4 and may decrease budesonide concentrations. Since budesonide has a wide therapeutic index, this is unlikely to be of clinical significance but monitoring of efficacy may be required.

Coadministration has not been studied. Buprenorphine undergoes both N-dealkylation to form norbuprenorphine (via CYP3A4) and glucuronidation (via UGT2B7 and UGT1A1). Dabrafenib is a strong inducer of CYP3A4 and a potential inducer of UGT. Concentrations of buprenorphine may decrease due to induction of CYP3A4 and UGT. Monitoring of buprenorphine efficacy is recommended. 

Coadministration has not been studied. Bupropion is primarily metabolised by CYP2B6. Dabrafenib is a potential inducer of CYP2B6 and may decrease concentrations of bupropion. Monitoring of bupropion efficacy is recommended. 

Coadministration has not been studied. Buspirone is metabolised by CYP3A4. Dabrafenib is an inducer of CYP3A4 and may decrease buspirone concentrations. Consider monitoring of buspirone efficacy.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Candesartan is mainly eliminated unchanged via urine and bile. Dabrafenib does not interfere with this elimination pathway.

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. Dabrafenib does not interfere with this elimination pathway. 

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. Dabrafenib is an inhibitor of OAT1 in vitro, but a clinically relevant interaction is unlikely.

Coadministration has not been studied but should be avoided. Carbamazepine is primarily metabolised by CYP3A4 and to a lesser extent by CYP2C8. Dabrafenib is an inducer of CYP3A4 and possibly CYP2C8. Therefore, dabrafenib may decrease concentrations of carbamazepine. Dose increments for carbamazepine should be considered. Monitor plasma concentrations, if available. Furthermore, carbamazepine is an inducer of CYPs 2C8 (strong), 2C9 (strong), 3A4 (strong), 1A2 (weak), 2B6 and UGT1A1. Dabrafenib concentrations may decrease due to CYP3A4 and CYP2C8 induction. A decrease in dabrafenib exposure can lead to decreased efficacy. Selection of an alternative concomitant medication with no or minimal enzyme induction potential is recommended. If coadministration is clinically necessary, consider monitoring of dabrafenib efficacy and plasma concentrations, if available. Increasing the dose of dabrafenib when co-administering with moderate or strong CYP3A and CYP2C8 inducers has not been studied and no formal dose advice can be given.

Coadministration has not been studied. Carvedilol undergoes glucuronidation via UGTs 1A1, 2B4 and 2B7, and metabolism via CYP2D6 and to a lesser extent by CYP2C9 and CYP1A2. Dabrafenib is an inducer of CYP2C9 and is a potential inducer of UGT. Concentrations of carvedilol may decrease due to induction of CYP3A4. As the clinical relevance of this interaction is unknown, monitoring of blood pressure and heart rate 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. Dabrafenib does not interfere with this metabolic pathway. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cefalexin is predominantly renally eliminated unchanged by glomerular filtration and tubular secretion via OAT1 and MATE1. Dabrafenib is an inhibitor of OAT1 in vitro but a clinically relevant interaction is unlikely.

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. Dabrafenib is an inhibitor of OAT3 in vitro but a clinically relevant interaction is unlikely.  

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cefixime is renally excreted predominantly by glomerular filtration. Dabrafenib does not interfere with this elimination pathway.

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. Dabrafenib is an inhibitor of OAT3 in vitro but a clinically relevant interaction is unlikely.

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

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. Dabrafenib does not interfere with this elimination pathway.

Coadministration has not been studied. Celecoxib is primarily metabolised by CYP2C9. Dabrafenib is a weak inducer of CYP2C9 and may decrease concentrations of celecoxib. Monitoring of celecoxib efficacy is recommended.

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. Dabrafenib is unlikely to interfere with this elimination pathway.

Coadministration has not been studied. Chloramphenicol is predominately glucuronidated. In vitro studies have shown that chloramphenicol is an inhibitor of CYP3A4 and may increase concentrations of dabrafenib, increasing the risk of adverse events. As the clinical significance of this interaction is unknown, close monitoring is recommended. Ocular use: Although chloramphenicol is systemically absorbed when used topically in the eye, the concentrations used are unlikely to cause a clinically significant interaction. 

Coadministration has not been studied. Chlordiazepoxide is extensively metabolised by CYP3A4. Dabrafenib is an inducer of CYP3A4 and may decrease chlordiazepoxide concentrations. Consider monitoring of chlordiazepoxide efficacy.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Chlorphenamine is predominantly metabolised in the liver via CYP2D6. Dabrafenib does not inhibit or induce CYP2D6. 

Coadministration has not been studied. Chlorpromazine is metabolised mainly by CYP2D6, but also by CYP1A2 and CYP3A4. Dabrafenib is an inducer of CYP3A4 and may decrease concentrations of chlorpromazine. The clinical relevance of this interaction is unknown. No clinically relevant QTc prolonging effects were observed after administration of dabrafenib (300 mg twice daily, two times the recommended dose). However, the incidences of QTc ≥501 msec and QTc increase of >60 msec from baseline were significantly higher with the combination dabrafenib-trametinib (4% and 13%, respectively) compared with trametinib (2% and 3%, respectively) and dabrafenib (<1% and 3%, respectively) monotherapies. Therefore, caution is needed when trametinib and dabrafenib are used concomitantly and are co-administered with a drug with a known risk of Torsade de Pointes. If coadministration with chlorpromazine is necessary, close monitoring including ECG assessment is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Chlortalidone is mainly excreted unchanged in the urine and faeces. Dabrafenib does not interfere with this elimination pathway. 

Coadministration has not been studied. Ciclosporin is metabolised by CYP3A4 and is a substrate of P-gp. Dabrafenib is an inducer of P-gp but a clinically relevant interaction is unlikely. Dabrafenib is also an inducer of CYP3A4 and may decrease ciclosporin concentrations. Ciclosporin is an inhibitor of CYP3A4 and OATP1B1 and may increase dabrafenib concentrations. No a priori dosage adjustment is recommended for dabrafenib, but close monitoring of toxicity is recommended. Monitoring for ciclosporin efficacy is recommended. Monitoring of cyclosporine plasma concentrations is recommended, if available. No clinically relevant QTc prolonging effects were observed after administration of dabrafenib (300 mg twice daily, two times the recommended dose). However, the incidences of QTc ≥501 msec and QTc increase of >60 msec from baseline were significantly higher with the combination dabrafenib-trametinib (4% and 13%, respectively) compared with trametinib (2% and 3%, respectively) and dabrafenib (<1% and 3%, respectively) monotherapies. Therefore, caution is needed when trametinib and dabrafenib are used concomitantly and are co-administered with a drug with a known risk of Torsade de Pointes. If coadministration with ciclosporin is necessary, close monitoring including ECG assessment is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cilazapril is mainly eliminated unchanged by the kidneys. Dabrafenib does not interfere with this elimination pathway.

Coadministration has not been studied. The aqueous solubility of dabrafenib is pH dependent with only a low solubility at pH 1. Coadministration of dabrafenib (150 mg twice daily) and rabeprazole (40 mg once daily) increased dabrafenib AUC by 3% and decreased dabrafenib Cmax by 12%. However, cimetidine is an inhibitor of CYP3A4 and may increase concentrations of dabrafenib. In vitro data indicate that cimetidine also inhibits OAT1 and OCT2 but at concentrations much higher than the observed clinical concentrations. As the clinical relevance of this interaction is unknown, monitoring of dabrafenib plasma concentrations may be required, if available.  

Coadministration has not been studied. Ciprofloxacin is primarily eliminated unchanged by the kidneys by glomerular filtration and tubular secretion via OAT3. It is also metabolised and partially cleared through the bile and intestine. Dabrafenib is an inhibitor of OAT3 in vitro, but this is unlikely to be clinically relevant. Ciprofloxacin is also a weak to moderate inhibitor of CYP3A4 and a strong inhibitor of CYP1A2. Concentrations of dabrafenib may increase due to inhibition of CYP3A4. Selection of an alternative concomitant medication with no or minimal enzyme or transporter inhibition potential is recommended. If coadministration is unavoidable, Close monitoring for dabrafenib toxicity is recommended. Consider monitoring of dabrafenib plasma concentrations, if available. No clinically relevant QTc prolonging effects were observed after administration of dabrafenib (300 mg twice daily, two times the recommended dose). However, the incidences of QTc ≥501 msec and QTc increase of >60 msec from baseline were significantly higher with the combination dabrafenib-trametinib (4% and 13%, respectively) compared with trametinib (2% and 3%, respectively) and dabrafenib (<1% and 3%, respectively) monotherapies. Therefore, caution is needed when trametinib and dabrafenib are used concomitantly and are co-administered with a drug with a known risk of Torsade de Pointes. If coadministration with ciprofloxacin is necessary, close monitoring including ECG assessment is recommended.

Coadministration has not been studied. Cisapride is metabolised by CYP3A4. Dabrafenib is an inducer of CYP3A4 and may decrease concentrations of cisapride. Monitoring of cisapride efficacy is recommended. No clinically relevant QTc prolonging effects were observed after administration of dabrafenib (300 mg twice daily, two times the recommended dose). However, the incidences of QTc ≥501 msec and QTc increase of >60 msec from baseline were significantly higher with the combination dabrafenib-trametinib (4% and 13%, respectively) compared with trametinib (2% and 3%, respectively) and dabrafenib (<1% and 3%, respectively) monotherapies. Therefore, caution is needed when trametinib and dabrafenib are used concomitantly and are co-administered with a drug with a known risk of Torsade de Pointes. If coadministration with cisapride is necessary, close monitoring including ECG assessment is recommended.

Coadministration has not been studied. Citalopram is metabolised by CYPs 2C19 (38%), 2D6 (31%) and 3A4 (31%). Dabrafenib is an inducer of CYP3A4 and is a potential inducer of CYP2C19. Concentrations of citalopram may decrease due to induction of CYP3A4. Monitoring of citalopram efficacy is recommended. No clinically relevant QTc prolonging effects were observed after administration of dabrafenib (300 mg twice daily, two times the recommended dose). However, the incidences of QTc ≥501 msec and QTc increase of >60 msec from baseline were significantly higher with the combination dabrafenib-trametinib (4% and 13%, respectively) compared with trametinib (2% and 3%, respectively) and dabrafenib (<1% and 3%, respectively) monotherapies. Therefore, caution is needed when trametinib and dabrafenib are used concomitantly and are co-administered with a drug with a known risk of Torsade de Pointes. If coadministration with citalopram is necessary, close monitoring including ECG assessment is recommended.

Coadministration has not been studied. Clarithromycin is metabolised by CYP3A4. Dabrafenib is a strong inducer of CYP3A4 and may decrease concentrations of clarithromycin. Clarithromycin is an inhibitor of CYP3A4 and P-gp and may increase concentrations of dabrafenib. Concurrent use of potent CYP3A4 inhibitors should be avoided due to dabrafenib toxicity. Selection of an alternative concomitant medication with no or minimal enzyme or transporter inhibition potential is recommended. If coadministration is unavoidable, close monitoring for dabrafenib toxicity and clarithromycin efficacy is recommended. Monitor dabrafenib plasma concentrations, 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. Dabrafenib does not interact with this metabolic or elimination 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. Dabrafenib does not inhibit or induce CYP2D6.

Coadministration has not been studied. Clindamycin is metabolised by CYP3A4. Dabrafenib is a strong inducer of CYP3A4 and may decrease concentrations of clindamycin. Due to the narrow therapeutic index of clindamycin, dose increments should be considered and monitoring of clindamycin efficacy 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 pharmacokinetic interaction is unlikely. Clofazimine is largely excreted unchanged in the faeces, both as unabsorbed drug and via biliary excretion. Dabrafenib does not interfere with this elimination pathway. No clinically relevant QTc prolonging effects were observed after administration of dabrafenib (300 mg twice daily, two times the recommended dose). However, the incidences of QTc ≥501 msec and QTc increase of >60 msec from baseline were significantly higher with the combination dabrafenib-trametinib (4% and 13%, respectively) compared with trametinib (2% and 3%, respectively) and dabrafenib (<1% and 3%, respectively) monotherapies. Therefore, caution is needed when trametinib and dabrafenib are used concomitantly and are co-administered with a drug with a known risk of Torsade de Pointes. If coadministration with clofazimine is necessary, close monitoring including ECG assessment is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clofibrate is hydrolysed to an active metabolite, clofibric acid. Excretion of clofibric acid glucuronide is possibly performed via OAT1. Dabrafenib is an inhibitor of OAT1 in vitro, but a clinically relevant interaction is unlikely.

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 both metabolised by CYP2D6. Dabrafenib is an inducer of CYP3A4 and is a potential inducer of CYP2C19. Concentrations of clomipramine may decrease and thus concentrations of desmethylclomipramine may increase due to induction of CYP3A4. Monitoring for desmethylclomipramine toxicity and efficacy is recommended. Monitor plasma concentration of clomipramine and active metabolite, if available. No clinically relevant QTc prolonging effects were observed after administration of dabrafenib (300 mg twice daily, two times the recommended dose). However, the incidences of QTc ≥501 msec and QTc increase of >60 msec from baseline were significantly higher with the combination dabrafenib-trametinib (4% and 13%, respectively) compared with trametinib (2% and 3%, respectively) and dabrafenib (<1% and 3%, respectively) monotherapies. Therefore, caution is needed when trametinib and dabrafenib are used concomitantly and are co-administered with a drug with a known risk of Torsade de Pointes. If coadministration with clomipramine is necessary, close monitoring including ECG assessment is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Approximately 70% of administered clonidine is excreted in the urine, mainly in the form of the unchanged parent drug (40-60% of the dose). Clonidine is a weak inhibitor of OCT2 and is unlikely to interact with dabrafenib elimination. In addition, dabrafenib 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. Dabrafenib is an inducer of CYP3A4 and is a potential inducer of CYP2B6 and CYP2C19. Concentrations of clopidogrel may decrease and thus concentrations of the active metabolite may increase due to induction of CYP3A4. Therefore, coadministration is not recommended due to the increased risk of bleeding. If coadministration is necessary, close monitoring for bleeding is recommended.

Coadministration has not been studied. Clorazepate is rapidly converted to nordiazepam which is then metabolised to oxazepam by CYP3A4. Dabrafenib is an inducer of CYP3A4 and may decrease clorazepate concentrations. Consider monitoring of clorazepate efficacy.

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

Coadministration has not been studied. Clozapine is metabolised mainly by CYP1A2 and CYP3A4 and to a lesser extent by CYP2C19 and CYP2D6. Dabrafenib is an inducer of CYP3A4 and a potential inducer of CYP2C19. Therefore, clozapine concentrations may decrease. Dose increments for clozapine should be considered. Monitor plasma concentrations, if available. No clinically relevant QTc prolonging effects were observed after administration of dabrafenib (300 mg twice daily, two times the recommended dose). However, the incidences of QTc ≥501 msec and QTc increase of >60 msec from baseline were significantly higher with the combination dabrafenib-trametinib (4% and 13%, respectively) compared with trametinib (2% and 3%, respectively) and dabrafenib (<1% and 3%, respectively) monotherapies. Therefore, caution is needed when trametinib and dabrafenib are used concomitantly and are co-administered with a drug with a known risk of Torsade de Pointes. If coadministration with clozapine is necessary, close monitoring including ECG assessment is recommended. Furthermore, due to the risk of additive haematological toxicity, haematological parameters should be monitored if coadministered with trametinib plus dabrafenib.

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. Although, dabrafenib is an inducer of P-gp, the risk of a clinically significant interaction is minimal. Furthermore, codeine is converted via CYP3A4 to norcodeine, an inactive metabolite. Dabrafenib is an inducer of CYP3A4 and may decrease concentrations of codeine and thereby decrease concentrations of morphine. Monitoring of codeine and morphine efficacy is recommended.

Coadministration has not been studied. Colchicine is metabolised by CYP3A4. Dabrafenib is an inducer of CYP3A4 and may decrease colchicine concentrations. As the clinical relevance of this interaction is unknown, monitoring of colchicine efficacy may be required.

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

Coadministration has not been studied. Dabigatran is transported via P-gp. Dabrafenib is an inducer of P-gp but the risk of a clinically significant interaction is minimal.

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. Dabrafenib does not interfere with this elimination pathway. 

Coadministration has not been studied. Metabolism of dapsone is mainly by N-acetylation with a component of N-hydroxylation, and is via multiple CYP450 enzymes. Dabrafenib is a strong inducer of CYP3A4 and also induces CYP2Cs and CYP2B6, and may decrease concentrations of dapsone. As the clinical relevance of this interaction is unknown, monitoring of dapsone efficacy may be required.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Desipramine is metabolised by CYP2D6. Dabrafenib does not inhibit or induce CYP2D6. No clinically relevant QTc prolonging effects were observed after administration of dabrafenib (300 mg twice daily, two times the recommended dose). However, the incidences of QTc ≥501 msec and QTc increase of >60 msec from baseline were significantly higher with the combination dabrafenib-trametinib (4% and 13%, respectively) compared with trametinib (2% and 3%, respectively) and dabrafenib (<1% and 3%, respectively) monotherapies. Therefore, caution is needed when trametinib and dabrafenib are used concomitantly and are co-administered with a drug with a known risk of Torsade de Pointes. If coadministration with desipramine is necessary, close monitoring including ECG assessment is recommended.

Coadministration has not been studied. Desogestrel is a prodrug which is activated to etonogestrel by CYP2C9 (and possibly CYP2C19); the metabolism of etonogestrel is mediated by CYP3A4. Dabrafenib is an inducer of CYP3A4 and CYP2C9, and is a potential inducer of CYP2C19. Concentrations of desogestrel may decrease and thus concentrations of etonogestrel may increase due to induction of CYP2C9, but concentrations of etonogestrel may also decrease due to induction of CYP3A4. The clinical relevance of this interaction is unknown. Dabrafenib may decrease the efficacy of desogestrel and women using hormonal contraceptives should add a barrier method as a second form of contraception while taking dabrafenib and for 1 month after stopping treatment.

Coadministration has not been studied. Dexamethasone is a known inducer of CYP3A4 and may decrease dabrafenib concentrations. The clinical relevance of this interaction is unknown as the induction effect of CYP3A4 by dexamethasone has not yet been established, but monitoring of dabrafenib efficacy may be required.

Coadministration has not been studied. Dextropropoxyphene is mainly metabolised by CYP3A4. Dabrafenib is a strong inducer of CYP3A4 and may decrease concentrations of dextropropoxyphene. Monitoring of dextropropoxyphene efficacy is recommended. 

Coadministration has not been studied. 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). Dabrafenib is a potential inducer of UGT and may decrease concentrations of diamorphine and thus increase concentrations of the active metabolite. Monitoring of diamorphine efficacy is recommended. 

Coadministration has not been studied. Diazepam is metabolised to nordiazepam (by CYP3A4 and CYP2C19) and to temazepam (mainly by CYP3A4). Dabrafenib is an inducer of CYP3A4 and a potential inducer of CYP2C19. Concentrations of diazepam may decrease due to induction of CYP3A4. Consider monitoring of diazepam efficacy.

Coadministration has not been studied. Diclofenac is partly glucuronidated by UGT2B7 and partly oxidised by CYP2C9. Dabrafenib is an inducer of CYP2C9 and a potential inducer of UGT. Concentrations of diclofenac may decrease due to induction of CYP2C9 and UGT. Monitoring of diclofenac efficacy is recommended.

Coadministration has not been studied. Digoxin is renally eliminated via the renal transporters OATP4C1 and P-gp. Dabrafenib is an inducer of P-gp and may decrease concentrations of digoxin. Since digoxin has a small therapeutic index, monitoring of digoxin plasma concentrations is recommended when dabrafenib is used concomitantly with digoxin and at discontinuation of dabrafenib. 

Coadministration has not been studied. Dihydrocodeine undergoes predominantly direct glucuronidation, with CYP3A4 mediated metabolism accounting for only 5-10% of the overall metabolism. Dabrafenib is a strong inducer of CYP3A4 and a potential inducer of UGT. Concentrations of dihydrocodeine may decrease due to induction of CYP3A4 and UGT. Monitoring of dihydrocodeine efficacy is recommended.

Coadministration has not been studied. Diltiazem is metabolised by CYP3A4 and CYP2D6. Dabrafenib is an inducer of CYP3A4 and may decrease diltiazem concentrations. Diltiazem is a moderate inhibitor of CYP3A4 and may increase dabrafenib concentrations. Coadministration should be avoided. Selection of an alternative concomitant medication with no or minimal enzyme or transporter inhibition potential is recommended. If coadministration is unavoidable, monitor closely for dabrafenib toxicity. Consider monitoring of dabrafenib plasma concentrations, if available.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Diphenhydramine is mainly metabolised by CYP2D6. Dabrafenib does not inhibit or induce CYP2D6. No clinically relevant QTc prolonging effects were observed after administration of dabrafenib (300 mg twice daily, two times the recommended dose). However, the incidences of QTc ≥501 msec and QTc increase of >60 msec from baseline were significantly higher with the combination dabrafenib-trametinib (4% and 13%, respectively) compared with trametinib (2% and 3%, respectively) and dabrafenib (<1% and 3%, respectively) monotherapies. Therefore, caution is needed when trametinib and dabrafenib are used concomitantly and are co-administered with a drug with a known risk of Torsade de Pointes. If coadministration with diphenhydramine is necessary, close monitoring including ECG assessment is recommended.

Coadministration has not been studied. Dipyridamole is glucuronidated by many UGTs, specifically those of the UGT1A subfamily. Dabrafenib is a potential inducer of UGT and may decrease concentrations of dipyridamole. Monitoring of dipyridamole efficacy is recommended. 

Coadministration has not been studied. Disopyramide is metabolised by CYP3A4 (25%) and 50% of the drug is eliminated unchanged in the urine. Dabrafenib is an inducer of CYP3A4 and may decrease concentrations of disopyramide. Since CYP3A4 mediated metabolism is a minor pathway, this is unlikely to be clinically significant but monitoring of disopyramide efficacy may be required. No clinically relevant QTc prolonging effects were observed after administration of dabrafenib (300 mg twice daily, two times the recommended dose). However, the incidences of QTc ≥501 msec and QTc increase of >60 msec from baseline were significantly higher with the combination dabrafenib-trametinib (4% and 13%, respectively) compared with trametinib (2% and 3%, respectively) and dabrafenib (<1% and 3%, respectively) monotherapies. Therefore, caution is needed when trametinib and dabrafenib are used concomitantly and are co-administered with a drug with a known risk of Torsade de Pointes. If coadministration with disopyramide is necessary, close monitoring including ECG assessment is recommended.

Coadministration has not been studied. 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%). Dabrafenib is an inducer of CYP3A4 and is a potential inducer of UGT. Concentrations of dolasetron may decrease due to induction of CYP3A4. Monitoring of dolasetron efficacy is recommended. No clinically relevant QTc prolonging effects were observed after administration of dabrafenib (300 mg twice daily, two times the recommended dose). However, the incidences of QTc ≥501 msec and QTc increase of >60 msec from baseline were significantly higher with the combination dabrafenib-trametinib (4% and 13%, respectively) compared with trametinib (2% and 3%, respectively) and dabrafenib (<1% and 3%, respectively) monotherapies. Therefore, caution is needed when trametinib and dabrafenib are used concomitantly and are co-administered with a drug with a known risk of Torsade de Pointes. If coadministration with dolasetron is necessary, close monitoring including ECG assessment is recommended.

Coadministration has not been studied. Domperidone is mainly metabolised by CYP3A4. Dabrafenib is an inducer of CYP3A4 and may decrease domperidone concentrations. Monitoring of domperidone efficacy is recommended. No clinically relevant QTc prolonging effects were observed after administration of dabrafenib (300 mg twice daily, two times the recommended dose). However, the incidences of QTc ≥501 msec and QTc increase of >60 msec from baseline were significantly higher with the combination dabrafenib-trametinib (4% and 13%, respectively) compared with trametinib (2% and 3%, respectively) and dabrafenib (<1% and 3%, respectively) monotherapies. Therefore, caution is needed when trametinib and dabrafenib are used concomitantly and are co-administered with a drug with a known risk of Torsade de Pointes. If coadministration with domperidone is necessary, close monitoring including ECG assessment is recommended.

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

Coadministration has not been studied. Doxazosin is metabolised mainly by CYP3A4. Dabrafenib is an inducer of CYP3A4 and may decrease doxazosin concentrations. Monitoring of blood pressure may be required. 

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. Dabrafenib is a potential inducer of CYP2C19 and may decrease concentrations of doxepin. Monitoring of doxepin efficacy is recommended.

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

Coadministration has not been studied. Dronabinol is mainly metabolised by CYP2C9 and to a lesser extent by CYP3A4. Dabrafenib is an inducer of CYP2C9 and CYP3A4, and may decrease concentrations of dronabinol. As the clinical relevance of this interaction is unknown, monitoring of dronabinol efficacy is recommended. 

Coadministration has not been studied. Drospirenone is metabolised to a minor extent via CYP3A4. Dabrafenib is an inducer of CYP3A4 and may decrease drospirenone concentrations. The clinical relevance of this interaction is unknown. Dabrafenib may decrease the efficacy of drospirenone and women using hormonal contraceptives should add a barrier method as a second form of contraception while taking dabrafenib and for 1 month after stopping treatment.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dulaglutide is degraded by endogenous endopeptidases. Dulaglutide delays gastric emptying and could possibly decrease the absorption rate of concomitantly administered oral drugs. Since dabrafenib efficacy is more likely to be correlated to trough plasma concentrations instead of maximum plasma concentrations of dabrafenib, the clinical relevance of delayed absorption is considered to be limited.

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

Coadministration has not been studied. Dutasteride is mainly metabolised by CYP3A4. Dabrafenib is an inducer of CYP3A4 and may decrease dutasteride concentrations. Although dutasteride has a wide therapeutic index, monitoring of efficacy may be required.

Coadministration has not been studied. Dydrogesterone is metabolised to dihydrodydrogesterone (possibly via CYP3A4). Dabrafenib is inducer of CYP3A4 and may decrease dydrogesterone concentrations. As the clinical relevance of this interaction is unknown, close monitoring may be required. 

Coadministration has not been studied. Edoxaban is partially metabolised by CYP3A4 (<10%) and is transported via P-gp. Dabrafenib is an inducer of P-gp but the risk of a clinically significant interaction is minimal. Dabrafenib is also an inducer of CYP3A4 and may decrease concentrations of edoxaban. As the clinical relevance of this interaction is unknown, monitoring may be required.

Coadministration has not been studied. Eltrombopag is metabolised by cleavage conjugation (via UGT1A1 and UGT1A3) and oxidation (via CYP1A2 and CYP2C8). Dabrafenib is a potential inducer of UGT and CYP2C8. Concentrations of eltrombopag may decrease due to induction of CYP2C8 and UGT. Monitoring of eltrombopag efficacy is recommended.

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). Dabrafenib is an inhibitor of OAT1/3 in vitro but a clinically relevant interaction is unlikely.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Eprosartan is largely excreted in bile and urine as unchanged drug. Dabrafenib does not interfere with this elimination pathway.

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

Coadministration has not been studied. Erythromycin is metabolised by CYP3A4. Dabrafenib is a strong inducer of CYP3A4 and may decrease concentrations of erythromycin. Erythromycin is also an inhibitor of CYP3A4 and may increase concentrations of dabrafenib. Concurrent use of potent CYP3A4 inhibitors should be avoided due to dabrafenib toxicity. Selection of an alternative concomitant medication with no or minimal enzyme inhibition potential is recommended. If coadministration is unavoidable, close monitoring for dabrafenib toxicity and erythromycin efficacy is recommended. Consider monitoring of dabrafenib plasma concentrations, if available. No clinically relevant QTc prolonging effects were observed after administration of dabrafenib (300 mg twice daily, two times the recommended dose). However, the incidences of QTc ≥501 msec and QTc increase of >60 msec from baseline were significantly higher with the combination dabrafenib-trametinib (4% and 13%, respectively) compared with trametinib (2% and 3%, respectively) and dabrafenib (<1% and 3%, respectively) monotherapies. Therefore, caution is needed when trametinib and dabrafenib are used concomitantly and are co-administered with a drug with a known risk of Torsade de Pointes. If coadministration with erythromycin is necessary, close monitoring including ECG assessment is recommended.

Coadministration has not been studied. Escitalopram is metabolised by CYPs 2C19 (37%), 2D6 (28%) and 3A4 (35%) to form N-desmethylescitalopram. Dabrafenib is an inducer of CYP3A4 and is a potential inducer of CYP2C19. Concentrations of escitalopram may decrease due to induction of CYP3A4. Monitoring of escitalopram efficacy is recommended. No clinically relevant QTc prolonging effects were observed after administration of dabrafenib (300 mg twice daily, two times the recommended dose). However, the incidences of QTc ≥501 msec and QTc increase of >60 msec from baseline were significantly higher with the combination dabrafenib-trametinib (4% and 13%, respectively) compared with trametinib (2% and 3%, respectively) and dabrafenib (<1% and 3%, respectively) monotherapies. Therefore, caution is needed when trametinib and dabrafenib are used concomitantly and are co-administered with a drug with a known risk of Torsade de Pointes. If coadministration with escitalopram is necessary, close monitoring including ECG assessment is recommended.

Coadministration has not been studied. The aqueous solubility of dabrafenib is pH dependent with only a low solubility at pH 1. Coadministration of dabrafenib (150 mg twice daily) and rabeprazole (40 mg once daily) increased dabrafenib AUC by 3% and decreased dabrafenib Cmax by 12%. Furthermore, esomeprazole is an inhibitor of CYP2C19. Dabrafenib does not interact with this pathway. Esomeprazole is metabolised by CYP2C19 and CYP3A4. Dabrafenib is an inducer of CYP3A4 and is a potential inducer of CYP2C19. Concentrations of esomeprazole may decrease due to induction of CYP3A4. As the clinical relevance of this interaction is unknown, monitoring of esomeprazole efficacy may be required.

Coadministration has not been studied. Estazolam is metabolised to its major metabolite 4-hydroxyestazolam via CYP3A4. Dabrafenib is an inducer of CYP3A4 and may decrease estazolam concentrations. Consider monitoring of estazolam efficacy.

Coadministration has not been studied. Estradiol is metabolised by CYP3A4, CYP1A2 and is glucuronidated. Dabrafenib is an inducer of CYP3A4 and is a potential inducer of UGT. Concentrations of estradiol may decrease due to induction of CYP3A4. The clinical relevance of this interaction is unknown. Dabrafenib may decrease the efficacy of estradiol and women using hormonal contraceptives should add a barrier method as a second form of contraception while taking dabrafenib and for 1 month after stopping treatment.

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

Coadministration has not been studied. Ethinylestradiol undergoes oxidation (CYP3A4>CYP2C9), sulfation and glucuronidation (UGT1A1). Dabrafenib is an inducer of CYP3A4 and is a potential inducer of UGT. Concentrations of ethinylestradiol may decrease due to induction of CYP3A4. The clinical relevance of this interaction is unknown. Dabrafenib may decrease the efficacy of ethinylestradiol and women using hormonal contraceptives should add a barrier method as a second form of contraception while taking dabrafenib and for 1 month after stopping treatment.

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

Coadministration has not been studied. Etonogestrel is metabolised by CYP3A4. Dabrafenib is an inducer of CYP3A4 and may decrease etonogestrel concentrations. The clinical relevance of this interaction is unknown. Dabrafenib may decrease the efficacy of etonogestrel and women using hormonal contraceptives should add a barrier method as a second form of contraception while taking dabrafenib and for 1 month after stopping treatment.

Everolimus is mainly metabolised by CYP3A4 and is a substrate of P-gp. Dabrafenib is an inducer of CYP3A4 and may decrease everolimus concentrations. In a single case report, coadministration of dabrafenib and everolimus resulted in a decreased exposure of everolimus. If coadministration is unavoidable, monitor plasma concentrations of everolimus very closely and adjust dose if necessary during initiation and discontinuation of dabrafenib.  

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Exenatide is cleared mainly by glomerular filtration. Exenatide delays gastric emptying and could possibly decrease the absorption rate of concomitantly administered oral drugs. Since dabrafenib efficacy is more likely to be correlated to trough plasma concentrations instead of maximum plasma concentrations of dabrafenib, the clinical relevance of delayed absorption is considered to be limited.

Coadministration has not been studied. Ezetimibe is glucuronidated by UGT1A1 and UGT1A3 and to a lesser extent by UGT2B15 and UGT2B7. Dabrafenib is a potential inducer of UGT and may decrease ezetimibe concentrations. Monitoring of cholesterol concentrations is recommended and adjust dose accordingly.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. The aqueous solubility of dabrafenib is pH dependent with only a low solubility at pH 1. Coadministration of dabrafenib (150 mg twice daily) and rabeprazole (40 mg once daily) increased dabrafenib AUC by 3% and decreased dabrafenib Cmax by 12%. Furthermore, famotidine is excreted via OAT1/OAT3. Dabrafenib is an inhibitor of OAT1/OAT3 in vitro but a clinically relevant interaction is unlikely.

Coadministration has not been studied. Felodipine is metabolised by CYP3A4. Dabrafenib is an inducer of CYP3A4 and may decrease felodipine concentrations. As the clinical relevance of this interaction is unknown, monitoring of blood pressure is recommended.

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

Coadministration has not been studied. Fentanyl undergoes extensive CYP3A4 metabolism. Dabrafenib is a strong inducer of CYP3A4 and may decrease concentrations of fentanyl. Monitoring of fentanyl efficacy 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. Dabrafenib does not interfere with this metabolic or elimination pathway.

Coadministration has not been studied. Finasteride is metabolised by CYP3A4. Dabrafenib is an inducer of CYP3A4 and may decrease finasteride concentrations. Although finasteride has a wide therapeutic index, monitoring of efficacy 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. Flecainide is metabolised mainly via CYP2D6, with a proportion (approximately 30%) of the parent drug also eliminated unchanged renally. Dabrafenib does not interact with this metabolic pathway. No clinically relevant QTc prolonging effects were observed after administration of dabrafenib (300 mg twice daily, two times the recommended dose). However, the incidences of QTc ≥501 msec and QTc increase of >60 msec from baseline were significantly higher with the combination dabrafenib-trametinib (4% and 13%, respectively) compared with trametinib (2% and 3%, respectively) and dabrafenib (<1% and 3%, respectively) monotherapies. Therefore, caution is needed when trametinib and dabrafenib are used concomitantly and are co-administered with a drug with a known risk of Torsade de Pointes. If coadministration with flecainide is necessary, close monitoring including ECG assessment is recommended.

Coadministration has not been studied. Flucloxacillin is mainly renally eliminated partly by glomerular filtration and partly by active secretion via OAT1. Dabrafenib is an inhibitor of OAT1 in vitro but this is unlikely to be clinically relevant. However, flucloxacillin is an inducer of CYP3A4 and P-gp and may decrease concentrations of dabrafenib. Close monitoring of dabrafenib efficacy is recommended.

Coadministration has not been studied. Fluconazole is cleared primarily by renal excretion. Dabrafenib is unlikely to interfere with this elimination pathway. However, fluconazole is an inhibitor of CYP3A4 and may increase concentrations of dabrafenib. Concurrent use of CYP3A4 inhibitors should be avoided. Selection of an alternative concomitant medication with no or minimal enzyme inhibition potential is recommended. If coadministration is unavoidable, close monitoring for dabrafenib toxicity is recommended. Consider monitoring of dabrafenib plasma concentrations, if available. No clinically relevant QTc prolonging effects were observed after administration of dabrafenib (300 mg twice daily, two times the recommended dose). However, the incidences of QTc ≥501 msec and QTc increase of >60 msec from baseline were significantly higher with the combination dabrafenib-trametinib (4% and 13%, respectively) compared with trametinib (2% and 3%, respectively) and dabrafenib (<1% and 3%, respectively) monotherapies. Therefore, caution is needed when trametinib and dabrafenib are used concomitantly and are co-administered with a drug with a known risk of Torsade de Pointes. If coadministration with fluconazole is necessary, close monitoring including ECG assessment is recommended.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Flucytosine is metabolised to 5-fluorouracil (5-FU). 5-FU is further metabolised by dihydropyrimidine dehydrogenase (DPD) to an inactive metabolite. Dabrafenib does not interfere with flucytosine 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. Dabrafenib plus trametinib 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 flucytosine is coadministered with dabrafenib plus trametinib.

Coadministration has not been studied. Fludrocortisone is metabolised in the liver to inactive metabolites, possibly via CYP3A. Dabrafenib is an inducer of CYP3A4 and may decrease fludrocortisone concentrations. Since fludrocortisone has a wide therapeutic index, this is unlikely to be of clinical significance, but monitoring of fludrocortisone efficacy may be required.

Coadministration has not been studied. Flunitrazepam is metabolised mainly via CYP3A4 and CYP2C19. Dabrafenib is an inducer of CYP3A4 and is a potential inducer of CYP2C19. Concentrations of flunitrazepam may decrease due to induction of CYP3A4. Consider monitoring of flunitrazepam efficacy.

Coadministration has not been studied. Fluoxetine is metabolised by CYP2D6 and CYP2C9 and to a lesser extent by CYP2C19 and CYP3A4 to form norfluoxetine. Dabrafenib is an inducer of CYP3A4, CYP2C9 and is a potential inducer of CYP2C19. Concentrations of fluoxetine may decrease due to induction of CYP3A4 and CYP2C9. Monitoring of fluoxetine efficacy is recommended.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Fluphenazine is metabolised by CYP2D6. Dabrafenib does not inhibit or induce CYP2D6. No clinically relevant QTc prolonging effects were observed after administration of dabrafenib (300 mg twice daily, two times the recommended dose). However, the incidences of QTc ≥501 msec and QTc increase of >60 msec from baseline were significantly higher with the combination dabrafenib-trametinib (4% and 13%, respectively) compared with trametinib (2% and 3%, respectively) and dabrafenib (<1% and 3%, respectively) monotherapies. Therefore, caution is needed when trametinib and dabrafenib are used concomitantly and are co-administered with a drug with a known risk of Torsade de Pointes. If coadministration with fluphenazine is necessary, close monitoring including ECG assessment is recommended.

Coadministration has not been studied. The metabolism of flurazepam is most likely CYP-mediated. Dabrafenib is an inducer of CYP3A4, CYP2C9 and is a potential inducer of CYPs 2B6, 2C8 and 2C19. Concentrations of flurazepam may decrease due to induction of CYP3A4 and CYP2C9. Consider monitoring of flurazepam efficacy.

Coadministration has not been studied. Fluticasone is metabolised by CYP3A4. Dabrafenib is an inducer of CYP3A4 and may decrease fluticasone concentrations. Since fluticasone has a wide therapeutic index, this is unlikely to be of clinical significance but monitoring of fluticasone efficacy may be required.

Coadministration has not been studied. Fluvastatin is mainly metabolised by CYP2C9. Dabrafenib is an inducer of CYP2C9 and may decrease fluvastatin concentrations. Monitoring of cholesterol concentrations is recommended and adjust dose accordingly.

Coadministration has not been studied. Fluvoxamine is metabolised mainly by CYP2D6 and to a lesser extent by CYP1A2. Fluvoxamine is an inhibitor of CYP3A4 and may increase concentrations of dabrafenib. As the clinical relevance of this interaction is unknown, monitoring for dabrafenib toxicity 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. Dabrafenib does not interact with this metabolic or elimination pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Formoterol is eliminated primarily by direct glucuronidation, with O-demethylation (by CYPs 2D6, 2C19, 2C9, and 2A6) followed by further glucuronidation. As multiple CYP450 and UGT enzymes catalyse 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. Dabrafenib does not interact with this metabolic pathway. Aprepitant is mainly metabolised by CYP3A4 and to a lesser extent by CYP1A2 and CYP2C19. Dabrafenib is an inducer of CYP3A4 and possibly of CYP2C19, and may decrease concentrations of aprepitant. Dose increments for aprepitant should be considered and monitoring of aprepitant efficacy may be required. Furthermore, during treatment aprepitant is a moderate inhibitor of CYP3A4 and may increase concentrations of dabrafenib during the three days of coadministration. Therefore, coadministration is not recommended. If coadministration is unavoidable, monitor closely for dabrafenib toxicity during the few days of coadministration and reduce the dabrafenib dose by 50%. After treatment, aprepitant is a weak inducer of CYP3A4, CYP2C9 and UGT. Concentrations of dabrafenib may decrease due to weak induction of CYP3A4, but this is not considered to be clinically relevant.

Coadministration has not been studied but should be avoided. Fosphenytoin is rapidly converted to the active metabolite phenytoin. Phenytoin is mainly metabolised by CYP2C9 and to a lesser extent by CYP2C19. Dabrafenib is an inducer of CYP2C9 and possibly of CYP2C19, and concentrations of phenytoin may decrease. If coadministration is unavoidable, monitor closely for phenytoin efficacy. Dose increments should be considered. Monitor phenytoin plasma concentrations, if available. Furthermore, phenytoin is a potent inducer of CYP3A4, UGT and P-gp. Concentrations of dabrafenib may decrease due to induction of CYP3A4. For one individual within a study (BRF113220) of patients with BRAF mutant metastatic melanoma, coadministration of dabrafenib (repeat doses of 150 mg twice daily) and phenytoin (300 mg twice daily) decreased dabrafenib AUC and Cmax by 62% and 77%, respectively. Hydroxy-dabrafenib and desmethyl-dabrafenib AUC and Cmax also decreased by 31% and 61%, and 63% and 73%, respectively.  Therefore, coadministration is not recommended, since a decrease in exposure can lead to decreased efficacy. Selection of an alternative concomitant medication with no or minimal enzyme or transporter induction potential is recommended. Increasing the dose of dabrafenib when coadministering with moderate or strong CYP3A inducers has not been studied therefore no formal dose advice can be given.

Coadministration has not been studied. 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. Dabrafenib is a potential inducer of UGT and may decrease furosemide concentrations. As the clinical relevance of this interaction is unknown, monitoring of furosemide efficacy is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Gabapentin is cleared mainly by glomerular filtration. Dabrafenib does not interfere with this elimination pathway.

Gemfibrozil is an inhibitor of CYP2C8 and may increase concentrations of dabrafenib. In patients with BRAF V600 mutation positive tumours (n=17), coadministration of dabrafenib (75 mg twice daily for 16 days) and gemfibrozil (600 mg twice daily for 4 days) increase dabrafenib AUC by 47% with no change in Cmax. Dabrafenib metabolites were also unaffected by gemfibrozil administration. Coadministration is not recommended. If coadministration is unavoidable, monitor for dabrafenib adverse reactions. Monitor dabrafenib plasma concentrations, if available.

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. Dabrafenib does not interfere with this elimination pathway. 

Coadministration has not been studied. Gestodene is metabolised by CYP3A4 and to a lesser extent by CYP2C9 and CYP2C19. Dabrafenib is an inducer of CYP3A4, CYP2C9 and is a potential inducer of CYP2C19. Concentrations of gestodene may decrease due to induction of CYP3A4 and CYP2C9. The clinical relevance of this interaction is unknown. Dabrafenib may decrease the efficacy of gestodene and women using hormonal contraceptives should add a barrier method as a second form of contraception while taking dabrafenib and for 1 month after stopping treatment.

Coadministration has not been studied. Glibenclamide is mainly metabolised by CYP3A4 and to a lesser extent by CYP2C9. Dabrafenib is an inducer of CYP3A4 and CYP2C9, and may decrease concentrations of glibenclamide. Monitoring of blood glucose levels is recommended.

Coadministration has not been studied. Gliclazide is metabolised mainly by CYP2C9 and to a lesser extent by CYP2C19. Dabrafenib is an inducer of CYP2C9 and is a potential inducer of CYP2C19. Concentrations of gliclazide may decrease due to induction of CYP2C9. Monitoring of blood glucose levels is recommended.

Coadministration has not been studied. Glimepiride is mainly metabolised by CYP2C9. Dabrafenib is an inducer of CYP2C9 and may decrease concentrations of glimepiride. Monitoring of blood glucose levels is recommended.

Coadministration has not been studied. Glipizide is mainly metabolised by CYP2C9. Dabrafenib is an inducer of CYP2C9 and may decrease concentrations of glipizide. Monitoring of blood glucose levels is recommended.

Coadministration has not been studied. Granisetron is metabolised by CYP3A4 and is a substrate of P-gp. Dabrafenib is an inducer of P-gp, but a clinically relevant interaction is unlikely. Dabrafenib is also an inducer of CYP3A4 and may decrease concentrations of granisetron. Monitoring of granisetron efficacy is recommended. No clinically relevant QTc prolonging effects were observed after administration of dabrafenib (300 mg twice daily, two times the recommended dose). However, the incidences of QTc ≥501 msec and QTc increase of >60 msec from baseline were significantly higher with the combination dabrafenib-trametinib (4% and 13%, respectively) compared with trametinib (2% and 3%, respectively) and dabrafenib (<1% and 3%, respectively) monotherapies. Therefore, caution is needed when trametinib and dabrafenib are used concomitantly and are co-administered with a drug with a known risk of Torsade de Pointes. If coadministration with granisetron is necessary, close monitoring including ECG assessment is recommended.

Grapefruit juice is a known inhibitor of CYP3A4 and may potentially increase dabrafenib concentrations. 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. Coadministration should be avoided. 

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. Dabrafenib does not interfere with this 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 dabrafenib. As the clinical relevance of this interaction is unknown, close monitoring is required.

Coadministration has not been studied. Haloperidol has a complex metabolism as it undergoes glucuronidation (UGTs 2B7>1A4, 1A9), carbonyl reduction as well as oxidative metabolism (CYP3A4 and CYP2D6). Dabrafenib is an inducer of CYP3A4 and is a potential inducer of UGT. Concentrations of haloperidol may decrease due to induction of CYP3A4. Monitoring of haloperidol efficacy is recommended. No clinically relevant QTc prolonging effects were observed after administration of dabrafenib (300 mg twice daily, two times the recommended dose). However, the incidences of QTc ≥501 msec and QTc increase of >60 msec from baseline were significantly higher with the combination dabrafenib-trametinib (4% and 13%, respectively) compared with trametinib (2% and 3%, respectively) and dabrafenib (<1% and 3%, respectively) monotherapies. Therefore, caution is needed when trametinib and dabrafenib are used concomitantly and are co-administered with a drug with a known risk of Torsade de Pointes. If coadministration with haloperidol is necessary, close monitoring including ECG assessment is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Heparin is thought to be eliminated via the reticuloendothelial system. Dabrafenib 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 dabrafenib. Dabrafenib does not interfere with the metabolism of hydralazine.

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. Dabrafenib is an inhibitor of OAT1 in vitro but a clinically relevant interaction is unlikely.

Coadministration has not been studied. Hydrocodone is metabolised by CYP2D6 to hydromorphone and by CYP3A4 to norhydrocodone, both of which have analgesic effects. Dabrafenib is a strong inducer of CYP3A4 and may decrease concentrations of hydrocodone and thus increase norhydrocodone concentrations. Therefore, monitoring for norhydrocodone toxicity is recommended. 

Coadministration has not been studied. Hydrocortisone is metabolised by CYP3A4. Dabrafenib is an inducer of CYP3A4 and may decrease hydrocortisone concentrations. Since hydrocortisone has a wide therapeutic index, this is unlikely to be of clinical significance but monitoring of hydrocortisone efficacy may be required.

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

Coadministration has not been studied. Hydromorphone is eliminated via glucuronidation, mainly by UGT2B7. Dabrafenib is a potential inducer of UGT and may decrease concentrations of hydromorphone. Monitoring of hydromorphone efficacy is recommended. 

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Hydroxyurea is not a substrate of CYP enzymes or P-gp. However, coadministration with dabrafenib and trametinib may increase risk of gastro-intestinal toxicity, haematological toxicity or mucositis. Due to the risk of additive haematological toxicity, haematological parameters should be monitored if coadministered with dabrafenib plus trametinib.

Coadministration has not been studied. Hydroxyzine is partly metabolised by alcohol dehydrogenase and partly by CYP3A4. Dabrafenib is an inducer of CYP3A4 and may decrease hydroxyzine concentrations. Consider monitoring of hydroxyzine efficacy. No clinically relevant QTc prolonging effects were observed after administration of dabrafenib (300 mg twice daily, two times the recommended dose). However, the incidences of QTc ≥501 msec and QTc increase of >60 msec from baseline were significantly higher with the combination dabrafenib-trametinib (4% and 13%, respectively) compared with trametinib (2% and 3%, respectively) and dabrafenib (<1% and 3%, respectively) monotherapies. Therefore, caution is needed when trametinib and dabrafenib are used concomitantly and are co-administered with a drug with a known risk of Torsade de Pointes. If coadministration with hydroxyzine is necessary, close monitoring including ECG assessment is recommended.

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

Coadministration has not been studied. Ibuprofen is metabolised mainly by CYP2C9 and to a lesser extent by CYP2C8 and direct glucuronidation. Dabrafenib is an inducer of CYP2C9 and potentially induces CYP2C8 and UGT. Concentrations of ibuprofen may decrease due to induction of CYP2C9, CYP2C8 and UGT. Monitoring of ibuprofen efficacy is recommended.

Coadministration has not been studied. Iloperidone is metabolised by CYP3A4 and CYP2D6. Dabrafenib is an inducer of CYP3A4 and may decrease concentrations of iloperidone. Monitoring of iloperidone efficacy is recommended. No clinically relevant QTc prolonging effects were observed after administration of dabrafenib (300 mg twice daily, two times the recommended dose). However, the incidences of QTc ≥501 msec and QTc increase of >60 msec from baseline were significantly higher with the combination dabrafenib-trametinib (4% and 13%, respectively) compared with trametinib (2% and 3%, respectively) and dabrafenib (<1% and 3%, respectively) monotherapies. Therefore, caution is needed when trametinib and dabrafenib are used concomitantly and are co-administered with a drug with a known risk of Torsade de Pointes. If coadministration with iloperidone is necessary, close monitoring including ECG assessment is recommended.

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

Coadministration has not been studied. Imipramine is metabolised by CYPs 3A4, 2C19 and 1A2 to desipramine. Imipramine and desipramine are both metabolised by CYP2D6. Dabrafenib is an inducer of CYP3A4 and is a potential inducer of CYP2C19. Concentrations of imipramine may decrease and thus concentrations of desipramine may increase due to induction of CYP3A4. Monitoring of imipramine efficacy and toxicity may be required. Monitor plasma concentration of imipramine and desipramine, if available. No clinically relevant QTc prolonging effects were observed after administration of dabrafenib (300 mg twice daily, two times the recommended dose). However, the incidences of QTc ≥501 msec and QTc increase of >60 msec from baseline were significantly higher with the combination dabrafenib-trametinib (4% and 13%, respectively) compared with trametinib (2% and 3%, respectively) and dabrafenib (<1% and 3%, respectively) monotherapies. Therefore, caution is needed when trametinib and dabrafenib are used concomitantly and are co-administered with a drug with a known risk of Torsade de Pointes. If coadministration with imipramine is necessary, close monitoring including ECG assessment is recommended.

Coadministration has not been studied. Indapamide is extensively metabolised by CYP450. Dabrafenib is an inducer of CYP2C9, CYP3A4 and is a potential inducer of CYPs 2C8, 2C19 and 2B6. Concentrations of indapamide may decrease due to induction of CYP3A4 and CYP2C9. As the clinical relevance of this interaction is unknown, monitoring of blood pressure is recommended. No clinically relevant QTc prolonging effects were observed after administration of dabrafenib (300 mg twice daily, two times the recommended dose). However, the incidences of QTc ≥501 msec and QTc increase of >60 msec from baseline were significantly higher with the combination dabrafenib-trametinib (4% and 13%, respectively) compared with trametinib (2% and 3%, respectively) and dabrafenib (<1% and 3%, respectively) monotherapies. Therefore, caution is needed when trametinib and dabrafenib are used concomitantly and are co-administered with a drug with a known risk of Torsade de Pointes. If coadministration with indapamide is necessary, close monitoring including ECG assessment is recommended.

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

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. However, coadministration may increase risk of neutropenia, fatigue, and thrombocytopenia. Due to the risk of additive haematological toxicity, haematological parameters should be monitored if coadministered with trametinib plus dabrafenib.

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. Dabrafenib does not interact with this elimination pathway.

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

Coadministration has not been studied. Irbesartan is metabolised by glucuronidation and oxidation (mainly CYP2C9). Dabrafenib is an inducer of CYP2C9 and is a potential inducer of UGT. Concentrations of irbesartan may decrease due to induction of CYP2C9. 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. Dabrafenib does not interfere with this metabolic pathway. 

Coadministration has not been studied. In vitro studies suggest that CYP3A4 has a role in nitric oxide formation from isosorbide dinitrate. Dabrafenib is an inducer of CYP3A4 and may decrease isosorbide concentrations. The clinical relevance of this interaction is unknown. 

Coadministration has not been studied. Itraconazole is metabolised by CYP3A4. Dabrafenib is an inducer of CYP3A4 and may decrease concentrations of itraconazole. Dose increments of itraconazole should be considered. Furthermore, itraconazole is a strong inhibitor of CYP3A4 and may increase concentrations of dabrafenib. Concurrent use of CYP3A4 inhibitors should be avoided. Selection of an alternative concomitant medication with no or minimal enzyme inhibition potential is recommended. If coadministration is unavoidable, close monitoring for dabrafenib toxicity and itraconazole efficacy is recommended. Consider monitoring of dabrafenib and itraconazole plasma concentrations, if available. No clinically relevant QTc prolonging effects were observed after administration of dabrafenib (300 mg twice daily, two times the recommended dose). However, the incidences of QTc ≥501 msec and QTc increase of >60 msec from baseline were significantly higher with the combination dabrafenib-trametinib (4% and 13%, respectively) compared with trametinib (2% and 3%, respectively) and dabrafenib (<1% and 3%, respectively) monotherapies. Therefore, caution is needed when trametinib and dabrafenib are used concomitantly and are co-administered with a drug with a known risk of Torsade de Pointes. If coadministration with itraconazole is necessary, close monitoring including ECG assessment is recommended.

Coadministration has not been studied. Ivabradine is metabolised by CYP3A4. Dabrafenib is an inducer of CYP3A4 and may decrease ivabradine concentrations. Monitoring of blood pressure and heart rate is recommended. No clinically relevant QTc prolonging effects were observed after administration of dabrafenib (300 mg twice daily, two times the recommended dose). However, the incidences of QTc ≥501 msec and QTc increase of >60 msec from baseline were significantly higher with the combination dabrafenib-trametinib (4% and 13%, respectively) compared with trametinib (2% and 3%, respectively) and dabrafenib (<1% and 3%, respectively) monotherapies. Therefore, caution is needed when trametinib and dabrafenib are used concomitantly and are co-administered with a drug with a known risk of Torsade de Pointes. If coadministration with ivabradine is necessary, close monitoring including ECG assessment is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Kanamycin is eliminated unchanged predominantly via glomerular filtration. Dabrafenib does not interfere with this elimination pathway.

Coadministration is not recommended. Ketoconazole is an inhibitor of CYP3A4 and may increase concentrations of dabrafenib. In patients with BRAF V600 mutation positive tumors (n=16), coadministration of ketoconazole (400 mg once daily for 4 days) and dabrafenib (75 mg once daily for 16 days) increased dabrafenib AUC and Cmax by 71% and 33%, respectively. The AUC of hydroxyl-dabrafenib and desmethyl-dabrafenib increased by 82% and 68%, respectively. The Cmax of hydroxyl-dabrafenib and desmethyl-dabrafenib increased by 27% and 72%, respectively. The AUC and Cmax of carboxy-dabrafenib decreased by 20%. Furthermore, ketoconazole is metabolised by CYP3A4. Dabrafenib is a strong inducer of CYP3A4 and may decrease ketoconazole concentrations. If coadministration is unavoidable, close monitoring for dabrafenib toxicity and ketoconazole efficacy is recommended. Consider monitoring of dabrafenib and ketoconazole plasma concentrations, if available. No clinically relevant QTc prolonging effects were observed after administration of dabrafenib (300 mg twice daily, two times the recommended dose). However, the incidences of QTc ≥501 msec and QTc increase of >60 msec from baseline were significantly higher with the combination dabrafenib-trametinib (4% and 13%, respectively) compared with trametinib (2% and 3%, respectively) and dabrafenib (<1% and 3%, respectively) monotherapies. Therefore, caution is needed when trametinib and dabrafenib are used concomitantly and are co-administered with a drug with a known risk of Torsade de Pointes. If coadministration with ketoconazole is necessary, close monitoring including ECG assessment is recommended.

Coadministration has not been studied. Labetalol is mainly glucuronidated (via UGT1A1 and UGT2B7). Dabrafenib is a potential inducer of UGT and may decrease labetalol concentrations. Monitoring of blood pressure may be required.

Coadministration has not been studied. Lacidipine is metabolised by CYP3A4. Dabrafenib is an inducer of CYP3A4 and may decrease lacidipine concentrations. 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. Dabrafenib is unlikely to interfere with this pathway.

Coadministration has not been studied. The aqueous solubility of dabrafenib is pH dependent with only a low solubility at pH 1. Coadministration of dabrafenib (150 mg twice daily) and rabeprazole (40 mg once daily) increased dabrafenib AUC by 3% and decreased dabrafenib Cmax by 12%. However, lansoprazole is mainly metabolised by CYP2C19 and to a lesser extent by CYP3A4. Dabrafenib is an inducer of CYP3A4 and is a potential inducer of CYP2C19. Concentrations of lansoprazole may decrease due to induction of CYP3A4. Consider monitoring of lansoprazole efficacy.

Coadministration has not been studied. Lercanidipine is mainly metabolised by CYP3A4. Dabrafenib is an inducer of CYP3A4 and may decrease lercanidipine concentrations. 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 levocetirizine is mainly eliminated unchanged in the urine through both glomerular filtration and tubular secretion. Dabrafenib does not interact with this metabolic or elimination pathway.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Levofloxacin is renally eliminated mainly by glomerular filtration and active secretion (possibly OCT2). Dabrafenib does not interact with this elimination pathway. No clinically relevant QTc prolonging effects were observed after administration of dabrafenib (300 mg twice daily, two times the recommended dose). However, the incidences of QTc ≥501 msec and QTc increase of >60 msec from baseline were significantly higher with the combination dabrafenib-trametinib (4% and 13%, respectively) compared with trametinib (2% and 3%, respectively) and dabrafenib (<1% and 3%, respectively) monotherapies. Therefore, caution is needed when trametinib and dabrafenib are used concomitantly and are co-administered with a drug with a known risk of Torsade de Pointes. If coadministration with levofloxacin is necessary, close monitoring including ECG assessment is recommended.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Levomepromazine is metabolised by CYP2D6. Dabrafenib does not inhibit or induce CYP2D6. No clinically relevant QTc prolonging effects were observed after administration of dabrafenib (300 mg twice daily, two times the recommended dose). However, the incidences of QTc ≥501 msec and QTc increase of >60 msec from baseline were significantly higher with the combination dabrafenib-trametinib (4% and 13%, respectively) compared with trametinib (2% and 3%, respectively) and dabrafenib (<1% and 3%, respectively) monotherapies. Therefore, caution is needed when trametinib and dabrafenib are used concomitantly and are co-administered with a drug with a known risk of Torsade de Pointes. If coadministration with levomepromazine is necessary, close monitoring including ECG assessment is recommended.

Coadministration has not been studied. Levonorgestrel is metabolised by CYP3A4 and is glucuronidated to a minor extent. Dabrafenib is an inducer of CYP3A4 and is a potential inducer of UGT. Concentrations of levonorgestrel may decrease due to induction of CYP3A4. The clinical relevance of this interaction is unknown. Dabrafenib may decrease the efficacy of levonorgestrel and women using hormonal contraceptives should add a barrier method as a second form of contraception while taking dabrafenib and for 1 month after stopping treatment.

Coadministration has not been studied. Levonorgestrel is metabolised by CYP3A4 and is glucuronidated to a minor extent. Dabrafenib is an inducer of CYP3A4 and is a potential inducer of UGT. Concentrations of levonorgestrel may decrease due to induction of CYP3A4. As the clinical relevance of this interaction is unknown, close monitoring may be required. 

Coadministration has not been studied. Levothyroxine is metabolised by deiodination (by enzymes of deiodinase family) and glucuronidation. Dabrafenib is a potential inducer of UGT and may decrease levothyroxine concentrations. Monitoring of levothyroxine efficacy is recommended in addition to monitoring TSH or free T4 concentrations, if available.

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. Dabrafenib is an inducer of CYP3A4 and may decrease concentrations of lidocaine. Since CYP3A4 mediated metabolism is only a minor pathway, a clinically relevant interaction is unlikely. 

Coadministration has not been studied. Linagliptin is mainly eliminated as parent compound in faeces with metabolism by CYP3A4 representing a minor elimination pathway. Linagliptin is also a substrate of P-gp and an inhibitor of CYP3A4. Dabrafenib is an inducer of CYP3A4 and may decrease concentrations of linagliptin. However, since CYP3A4 mediated metabolism is a minor pathway, this is unlikely to be of clinical significance. Dabrafenib is also an inducer of P-gp but the risk of a clinically significant interaction is minimal. Linagliptin is an inhibitor of CYP3A4 and may increase concentrations of dabrafenib. As the clinical relevance of this interaction is unknown, monitoring may be required.  

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Linezolid undergoes non-CYP mediated metabolism. Dabrafenib is unlikely to interfere with this metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Liraglutide is degraded by endogenous endopeptidases. Dabrafenib is unlikely to interfere with this pathway.

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. Dabrafenib does not interact with this elimination pathway.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Lithium is mainly eliminated unchanged through the kidneys. Lithium is freely filtered at a rate that is dependent upon the glomerular filtration rate and no pharmacokinetic interaction is expected. No clinically relevant QTc prolonging effects were observed after administration of dabrafenib (300 mg twice daily, two times the recommended dose). However, the incidences of QTc ≥501 msec and QTc increase of >60 msec from baseline were significantly higher with the combination dabrafenib-trametinib (4% and 13%, respectively) compared with trametinib (2% and 3%, respectively) and dabrafenib (<1% and 3%, respectively) monotherapies. Therefore, caution is needed when trametinib and dabrafenib are used concomitantly and are co-administered with a drug with a known risk of Torsade de Pointes. If coadministration with lithium is necessary, close monitoring including ECG assessment is recommended.

Coadministration of live vaccines (such as BCG vaccine; measles, mumps and rubella vaccines; varicella vaccines; typhoid vaccines; rotavirus vaccines; yellow fever vaccines; oral polio vaccine) has not been studied. In patients, who are receiving cytotoxics or other immunosuppressant drugs, use of live vaccines for immunisation is contraindicated. If coadministration is judged clinically necessary, use with extreme caution since generalised 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. Dabrafenib is an inducer of CYP3A4 and is a potential inducer of CYP2C8. Concentrations of loperamide may decrease due to induction of CYP3A4, but this is unlikely to be clinically relevant due to the wide therapeutic index of loperamide.

Coadministration has not been studied. Loratadine is metabolised mainly by CYP3A4 and to a lesser extent by CYP2D6. Dabrafenib is an inducer of CYP3A4 and may decrease loratadine concentrations. However, this is unlikely to be clinically relevant as loratadine has a wide therapeutic index but monitoring of loratadine efficacy may be required.

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 dabrafenib. 

Coadministration has not been studied. Lormetazepam is mainly glucuronidated. Dabrafenib is a potential inducer of UGT and may decrease concentrations of lormetazepam. Consider monitoring of lormetazepam efficacy.

Coadministration has not been studied. Losartan is converted to its active metabolite mainly by CYP2C9 in the range of clinical concentrations. Dabrafenib is an inducer of CYP2C9 and may decrease losartan plasma exposure. Monitoring of blood pressure is recommended. 

Coadministration has not been studied. Lovastatin is metabolised by CYP3A4. Dabrafenib is an inducer of CYP3A4 and may decrease lovastatin exposure. Monitoring of cholesterol concentrations is recommended and adjust dose accordingly.

Coadministration has not been studied. Macitentan is metabolised mainly by CYP3A4 and to a lesser extent by CYPs 2C19, 2C9 and 2C8. Dabrafenib is an inducer of CYP3A4, CYP2C9 and is a potential inducer of CYP2C19 and CYP2C8. Concentrations of macitentan may decrease due to induction of CYP3A4 and CYP2C9. 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 the kidney, mainly by glomerular filtration. Dabrafenib does not interfere with this elimination pathway. 

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

Coadministration has not been studied. Medroxyprogesterone is metabolised by CYP3A4. Dabrafenib is an inducer of CYP3A4 and may decrease medroxyprogesterone concentrations. The clinical relevance of this interaction is unknown. Dabrafenib may decrease the efficacy of medroxyprogesterone and women using hormonal contraceptives should add a barrier method as a second form of contraception while taking dabrafenib and for 1 month after stopping treatment.

Coadministration has not been studied. Medroxyprogesterone is metabolised by CYP3A4. Dabrafenib is an inducer of CYP3A4 and may decrease medroxyprogesterone concentrations. The clinical relevance of this interaction is unknown. Dabrafenib may decrease the efficacy of medroxyprogesterone and women using hormonal contraceptives should add a barrier method as a second form of contraception while taking dabrafenib and for 1 month after stopping treatment.

Coadministration has not been studied. Mefenamic acid is metabolised by CYP2C9 and glucuronidated by UGT2B7 and UGT1A9. Dabrafenib is an inducer of CYP2C9 and a potential inducer of UGT. Concentrations of mefenamic acid may decrease due to induction of CYP2C9, UGT2B7 and UGT1A9. Monitoring of mefenamic acid efficacy is recommended. 

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. Dabrafenib is unlikely to interact with this elimination pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Meropenem is primarily eliminated by the kidney with in vitro data suggesting it is a substrate of the renal transporters OAT3>OAT1. Dabrafenib is an inhibitor of OAT1 and OAT3 in vitro but this is unlikely to be clinically relevant. 

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. Dabrafenib does not interfere with this metabolic pathway. 

Coadministration has not been studied. Metamizole is metabolised by hydrolysis to the active metabolite MAA in the gastrointestinal tract. Subsequently, MMA is metabolised by CYPs. Metamizole is excreted via urine (90%) and faeces (10%) as metabolites. Dabrafenib is an inducer of CYP3A4 and may decrease concentrations of MMA. Monitoring for metamizole efficacy should be considered. Metamizole is also an inducer of CYP3A4 and may decrease dabrafenib concentrations. As the clinical relevance of this interaction is unknown, monitoring may be required.

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

Coadministration has not been studied. Methadone is demethylated by CYP3A4. Dabrafenib is an inducer of CYP3A4 and may decrease concentrations of methadone. As the clinical relevance of this interaction is unknown, monitoring of methadone efficacy is recommended. No clinically relevant QTc prolonging effects were observed after administration of dabrafenib (300 mg twice daily, two times the recommended dose). However, the incidences of QTc ≥501 msec and QTc increase of >60 msec from baseline were significantly higher with the combination dabrafenib-trametinib (4% and 13%, respectively) compared with trametinib (2% and 3%, respectively) and dabrafenib (<1% and 3%, respectively) monotherapies. Therefore, caution is needed when trametinib and dabrafenib are used concomitantly and are co-administered with a drug with a known risk of Torsade de Pointes. If coadministration with methadone is necessary, close monitoring including ECG assessment is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Methyldopa is excreted in urine largely by glomerular filtration, primarily unchanged and as the mono-O-sulfate conjugate. It is unlikely to affect the disposition of dabrafenib or to be altered by coadministration with dabrafenib.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Methylphenidate is not metabolised by CYP450 to a clinically relevant extent and does not inhibit or induce CYP450s. 

Coadministration has not been studied. Methylprednisolone is metabolised by CYP3A4. Dabrafenib is an inducer of CYP3A4 and may decrease methylprednisolone concentrations. Since methylprednisolone has a wide therapeutic index, this is unlikely to be of clinical significance but monitoring of methylprednisolone efficacy may be required.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metolazone is largely excreted unchanged in the urine. Dabrafenib does not interfere with this elimination pathway.

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

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 dabrafenib cannot be excluded and close monitoring for toxicity is recommended.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Mianserin is metabolised by CYP2D6 and CYP1A2, and to a lesser extent by CYP3A4. Dabrafenib is an inducer of CYP3A4. The clinical relevance of this interaction is unknown but since CYP3A4 mediated metabolism is only a minor pathway, a clinically relevant interaction is unlikely.

Coadministration has not been studied. Miconazole inhibits CYP2C9 and CYP3A4 and may increase dabrafenib concentrations. Oromucosal coadministration may increase dabrafenib concentrations due to inhibition of CYP3A4. Concurrent use of CYP3A4 inhibitors should be avoided. Selection of an alternative concomitant medication with no or minimal enzyme inhibition potential is recommended. If coadministration is unavoidable, monitor closely for dabrafenib toxicity. Consider monitoring of dabrafenib plasma concentrations, if available. No clinically relevant QTc prolonging effects were observed after administration of dabrafenib (300 mg twice daily, two times the recommended dose). However, the incidences of QTc ≥501 msec and QTc increase of >60 msec from baseline were significantly higher with the combination dabrafenib-trametinib (4% and 13%, respectively) compared with trametinib (2% and 3%, respectively) and dabrafenib (<1% and 3%, respectively) monotherapies. Therefore, caution is needed when trametinib and dabrafenib are used concomitantly and are co-administered with a drug with a known risk of Torsade de Pointes. If coadministration with miconazole is necessary, close monitoring including ECG assessment is recommended.

Midazolam is metabolised by CYP3A4. Dabrafenib is an inducer of CYP3A4 and may decrease concentrations of midazolam. Coadministration of dabrafenib (150 mg twice daily) and midazolam (single dose) decreased midazolam AUC and Cmax by 74% and 61%, respectively. Dose increments of midazolam may be necessary and monitoring of midazolam efficacy is recommended.

Midazolam is metabolised by CYP3A4. Dabrafenib is an inducer of CYP3A4 and may decrease concentrations of midazolam. Coadministration of dabrafenib (150 mg twice daily) and oral midazolam (single dose) decreased midazolam AUC and Cmax by 74% and 61%, respectively. Dose increments of midazolam may be necessary and monitoring of midazolam efficacy is recommended.

Coadministration has not been studied. Milnacipran is mainly eliminated unchanged (50%), and as glucuronides (30%) and oxidative metabolites (20%). Dabrafenib is a potential inducer of UGT and may decrease concentrations of milnacipran. Monitoring of milnacipran efficacy is recommended.

Coadministration has not been studied. Mirtazapine is metabolised to 8-hydroxymirtazapine by CYP2D6 and CYP1A2, and to N-desmethylmirtazapine mainly by CYP3A4. Dabrafenib is an inducer of CYP3A4 and may decrease concentrations of mirtazapine and thus increase concentrations of desmethylmirtazapine. Monitoring of mirtazapine efficacy and desmethylmirtazapine toxicity is recommended.

Coadministration has not been studied. Mometasone is metabolised by CYP3A4. Dabrafenib is an inducer of CYP3A4 and may decrease mometasone concentrations. Since mometasone has a wide therapeutic index, this is unlikely to be of clinical significance but monitoring of mometasone efficacy may be required.

Coadministration has not been studied. Montelukast is mainly metabolised by CYP2C8 and to a lesser extent by CYP3A4 and CYP2C9. Dabrafenib is an inducer of CYP3A4, CYP2C9 and is a potential inducer of CYP2C8. Concentrations of montelukast may decrease due to induction of CYP3A4 and CYP2C9. Monitoring of montelukast efficacy is recommended.

Coadministration has not been studied. Morphine is mainly glucuronidated to morphine-3-glucuronide (UGT2B7>UGT1A1) and, to a lesser extent, to the pharmacologically active morphine-6-glucuronide (UGT2B7>UGT1A1). Dabrafenib is a potential inducer of UGT and may decrease concentrations of morphine. Monitoring of morphine efficacy is recommended.

Coadministration has not been studied. Moxifloxacin is predominantly glucuronidated by UGT1A1. Dabrafenib is a potential inducer of UGT and may decrease concentrations of moxifloxacin. Monitoring of moxifloxacin efficacy is recommended. Monitoring of plasma concentrations of moxifloxacin should be considered, if available. No clinically relevant QTc prolonging effects were observed after administration of dabrafenib (300 mg twice daily, two times the recommended dose). However, the incidences of QTc ≥501 msec and QTc increase of >60 msec from baseline were significantly higher with the combination dabrafenib-trametinib (4% and 13%, respectively) compared with trametinib (2% and 3%, respectively) and dabrafenib (<1% and 3%, respectively) monotherapies. Therefore, caution is needed when trametinib and dabrafenib are used concomitantly and are co-administered with a drug with a known risk of Torsade de Pointes. If coadministration with moxifloxacin is necessary, close monitoring including ECG assessment is recommended.

Coadministration has not been studied. Mycophenolate is mainly glucuronidated by UGT1A9 and UGT2B7. Dabrafenib is a potential inducer of UGT and may decrease mycophenolate concentrations. Monitoring of mycophenolate plasma concentrations is recommended. Coadministration may also increase the risk of neutropenia, fatigue, and thrombocytopenia. Due to the risk of additive haematological toxicity, haematological parameters should be monitored if coadministered with trametinib and dabrafenib.

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. Dabrafenib 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. Dabrafenib does not interact with this pathway.

Coadministration has not been studied. Naproxen is mainly glucuronidated by UGT2B7 (major) and demethylated to desmethylnaproxen by CYP2C9 (major) and CYP1A2. Dabrafenib is an inducer of CYP2C9 and potentially induces UGT. Concentrations of naproxen may decrease due to induction of CYP2C9 and UGT. Monitoring of naproxen efficacy is recommended. 

Coadministration has not been studied. Nateglinide is mainly metabolised by CYP2C9 (70%) and to a lesser extent by CYP3A4 (30%). Dabrafenib is an inducer of CYP2C9 and CYP3A4, and may decrease concentrations of nateglinide. Monitoring of blood glucose levels is recommended.

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

Coadministration has not been studied. Nefazodone is a substrate of CYP3A4. Dabrafenib is an inducer of CYP3A4 and may decrease concentrations of nefazodone. Monitoring of nefazodone efficacy is recommended. Nefazodone is an inhibitor of CYP3A4 and may increase concentrations of dabrafenib. Concurrent use of CYP3A4 inhibitors should be avoided. Selection of an alternative concomitant medication with no or minimal enzyme inhibition potential is recommended. If coadministration is unavoidable, close monitoring for dabrafenib toxicity is recommended. Consider monitoring of dabrafenib plasma concentrations, if available. Note: No clinically relevant QTc prolonging effects were observed after administration of dabrafenib (300 mg twice daily, two times the recommended dose). However, the incidences of QTc ≥501 msec and QTc increase of >60 msec from baseline were significantly higher with the combination dabrafenib-trametinib (4% and 13%, respectively) compared with trametinib (2% and 3%, respectively) and dabrafenib (<1% and 3%, respectively) monotherapies. Therefore, caution is needed when trametinib and dabrafenib are used concomitantly and are co-administered with a drug with a known risk of Torsade de Pointes. If coadministration with nefazodone is necessary, close monitoring including ECG assessment is recommended.

Coadministration has not been studied. Nicardipine is metabolised mainly by CYP3A4 and to a lesser extent by CYP2D6 and CYP2C8. Dabrafenib is an inducer of CYP3A4 and is a potential inducer of CYP2C8. Concentrations of nicardipine may decrease due to induction of CYP3A4. As the clinical relevance of this interaction is unknown, monitoring of blood pressure is recommended. Nicardipine is an inhibitor of CYP3A4 and may increase dabrafenib concentrations. No a priori dosage adjustment is recommended for dabrafenib but close monitoring of dabrafenib tolerability may be necessary. 

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. Dabrafenib does not interact with this metabolic pathway.

Coadministration has not been studied. Nifedipine is metabolised mainly by CYP3A4. Dabrafenib is an inducer of CYP3A4 and may decrease nifedipine concentrations. As the clinical relevance of this interaction is unknown, monitoring of blood pressure is recommended.

Coadministration has not been studied. Nimesulide is extensively metabolised in the liver following multiple pathways including CYP2C9. Dabrafenib is an inducer of CYP2C9 and may decrease concentrations of nimesulide. Monitoring of nimesulide efficacy is recommended.

Coadministration has not been studied. Nisoldipine is metabolised by CYP3A4. Dabrafenib is an inducer of CYP3A4 and may decrease nisoldipine concentrations. As the clinical relevance of this interaction is unknown, monitoring of blood pressure is recommended.

Coadministration has not been studied. Nitrendipine is extensively metabolised mainly by CYP3A4. Dabrafenib is an inducer of CYP3A4 and may decrease nitrendipine concentrations. As the clinical relevance of this interaction is unknown, monitoring of blood pressure is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nitrofurantoin is partly metabolised in the liver via glucuronidation and N-acetylation and partly eliminated in the urine as unchanged drug (30-40%). Dabrafenib is a potential inducer of UGT and may decrease concentrations of nitrofurantoin. Monitoring of nitrofurantoin efficacy is recommended.

Coadministration has not been studied. Norelgestromin is metabolised to norgestrel (possibly by CYP3A4). Dabrafenib is an inducer of CYP3A4 and may decrease norelgestromin concentrations. The clinical relevance of this interaction is unknown. Dabrafenib may decrease the efficacy of norelgestromin and women using hormonal contraceptives should add a barrier method as a second form of contraception while taking dabrafenib and for 1 month after stopping treatment.

Coadministration has not been studied. Norethisterone is extensively biotransformed, first by reduction and then by sulfate and glucuronide conjugation. Dabrafenib is a potential inducer of UGT and may decrease norethisterone concentrations. The clinical relevance of this interaction is unknown. Dabrafenib may decrease the efficacy of norethisterone and women using hormonal contraceptives should add a barrier method as a second form of contraception while taking dabrafenib and for 1 month after stopping treatment.

Coadministration has not been studied. Norgestimate is rapidly deacetylated to the active metabolite which is further metabolised via CYP450. Dabrafenib is an inducer of CYP3A4, CYP2C9 and is a potential inducer of CYPs 2B6, 2C19 and 2C8. Concentrations of norgestimate may decrease due to induction of CYP3A4 and CYP2C9. The clinical relevance of this interaction is unknown. Dabrafenib may decrease the efficacy of norgestimate and women using hormonal contraceptives should add a barrier method as a second form of contraception while taking dabrafenib and for 1 month after stopping treatment.

Coadministration has not been studied. Norgestrel is a racemic mixture with levonorgestrel being biologically active. Levonorgestrel is mainly metabolised by CYP3A4. Dabrafenib is an inducer of CYP3A4 and may decrease levonorgestrel concentrations. The clinical relevance of this interaction is unknown. Dabrafenib may decrease the efficacy of norgestrel and women using hormonal contraceptives should add a barrier method as a second form of contraception while taking dabrafenib and for 1 month after stopping treatment.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Nortriptyline is metabolised mainly by CYP2D6. Dabrafenib does not inhibit or induce CYP2D6. No clinically relevant QTc prolonging effects were observed after administration of 300 mg dabrafenib twice daily (two times the recommended dose). However, the incidences of QTc ≥501 msec and of QTc increase of >60 msec from baseline were significantly higher with the combination dabrafenib-trametinib (4% and 13%, respectively) compared with the trametinib (2% and 3%, respectively) and the dabrafenib (<1% and 3%, respectively) monotherapy populations. Therefore, caution is needed when trametinib and dabrafenib are used concomitantly and are co-administered with a drug with a known risk of Torsade de Pointes. If coadministration with nortriptyline is necessary, close monitoring including ECG assessment is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Systemic absorption of nystatin from oral or topical dosage forms is not significant, therefore no drug interactions are expected. 

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Ofloxacin is renally eliminated unchanged by glomerular filtration and active tubular secretion via both cationic and anionic transport systems. Dabrafenib is unlikely to interfere with this elimination pathway. No clinically relevant QTc prolonging effects were observed after administration of dabrafenib (300 mg twice daily, two times the recommended dose). However, the incidences of QTc ≥501 msec and QTc increase of >60 msec from baseline were significantly higher with the combination dabrafenib-trametinib (4% and 13%, respectively) compared with trametinib (2% and 3%, respectively) and dabrafenib (<1% and 3%, respectively) monotherapies. Therefore, caution is needed when trametinib and dabrafenib are used concomitantly and are co-administered with a drug with a known risk of Torsade de Pointes. If coadministration with ofloxacin is necessary, close monitoring including ECG assessment is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Olanzapine is metabolised mainly by CYP1A2 and CYP2D6, but also by glucuronidation (UGT1A4). Dabrafenib is a potential inducer of UGT and may decrease olanzapine concentrations, but since UGT is only a minor pathway, this is unlikely to be clinically relevant.

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. Dabrafenib does not interfere with this pathway.

Coadministration has not been studied. The aqueous solubility of dabrafenib is pH dependent with only a low solubility at pH 1. Coadministration of dabrafenib (150 mg twice daily) and rabeprazole (40 mg once daily) increased dabrafenib AUC by 3% and decreased dabrafenib Cmax by 12%. However, omeprazole is an inducer of CYP1A2 and an inhibitor of CYP2C19. Dabrafenib does not interact with this pathway. Furthermore, omeprazole is mainly metabolised by CYP2C19 and to a lesser extent by CYP3A4. Dabrafenib is an inducer of CYP3A4 and is a potential inducer of CYP2C19. Concentrations of omeprazole may decrease due to induction of CYP3A4. Consider monitoring of omeprazole efficacy.

Coadministration has not been studied. Ondansetron is metabolised mainly by CYP1A2, CYP3A4 and to a lesser extent by CYP2D6. Ondansetron is a substrate of P-gp. Dabrafenib is an inducer of P-gp, but a clinically relevant interaction is unlikely. Dabrafenib is also an inducer of CYP3A4 and may decrease concentrations of ondansetron. Monitoring of ondansetron efficacy is recommended. No clinically relevant QTc prolonging effects were observed after administration of dabrafenib (300 mg twice daily, two times the recommended dose). However, the incidences of QTc ≥501 msec and QTc increase of >60 msec from baseline were significantly higher with the combination dabrafenib-trametinib (4% and 13%, respectively) compared with trametinib (2% and 3%, respectively) and dabrafenib (<1% and 3%, respectively) monotherapies. Therefore, caution is needed when trametinib and dabrafenib are used concomitantly and are co-administered with a drug with a known risk of Torsade de Pointes. If coadministration with ondansetron is necessary, close monitoring including ECG assessment is recommended.

Coadministration has not been studied. Oxazepam is mainly glucuronidated. Dabrafenib is a potential inducer of UGT and may decrease concentrations of oxazepam. However, since oxazepam does not have a narrow therapeutic index, this is unlikely to be clinically relevant but consider monitoring of oxazepam efficacy. 

Coadministration has not been studied but should be avoided. Oxcarbazepine is extensively metabolised to the active metabolite monohydroxyderivate (MHD) through cystolic enzymes. Dabrafenib does not interfere with this pathway. Both oxcarbazepine and MHD are inducers of CYP3A4 (moderate) and CYP3A5, and inhibitors of CYP2C19. Dabrafenib concentrations may be significantly decreased due to induction of CYP3A4. Decreased dabrafenib exposure can lead to decreased efficacy. Selection of an alternative concomitant medication with no or minimal enzyme induction potential is recommended. If coadministration is clinically necessary, consider monitoring of dabrafenib efficacy and plasma concentrations, if available. Increasing the dose of dabrafenib when co-administering with moderate or strong CYP3A inducers has not been studied and no formal dose advice can be given.

Coadministration has not been studied. Oxprenolol is largely metabolised via glucuronidation. Dabrafenib is a potential inducer of UGT and may decrease concentrations of oxprenolol. Monitoring of blood pressure is recommended.

Coadministration has not been studied. Oxycodone is metabolised principally to noroxycodone via CYP3A and oxymorphone via CYP2D6. Dabrafenib is a strong inducer of CYP3A4 and may decrease concentrations of oxycodone. Monitoring for oxycodone efficacy is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Paliperidone is primarily renally eliminated (possibly via OCT) with minimal metabolism occurring via CYP2D6 and CYP3A4. Dabrafenib is a strong inducer of CYP3A4 and may decrease paliperidone concentrations. As the clinical relevance of this interaction is unknown, monitoring for paliperidone efficacy may be required.

Coadministration has not been studied. Palonosetron is metabolised mainly by CYP2D6 and to a lesser extent by CYP3A4 and CYP1A2. Palonosetron is also a substrate of P-gp. Dabrafenib is an inducer of P-gp, but a clinically relevant interaction is unlikely. Dabrafenib is also an inducer of CYP3A4 and may decrease concentrations of palonosetron. Monitoring of palonosetron efficacy is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pamidronic acid is not metabolised and is cleared as unchanged drug via urine. Dabrafenib does not interact with this elimination pathway.

Coadministration has not been studied. The aqueous solubility of dabrafenib is pH dependent with only a low solubility at pH 1. Coadministration of dabrafenib (150 mg twice daily) and rabeprazole (40 mg once daily) increased dabrafenib AUC by 3% and decreased dabrafenib Cmax by 12%. However, pantoprazole is mainly metabolised by CYP2C19 and to a lesser extent by CYPs 3A4, 2D6 and 2C9. Dabrafenib is an inducer of CYP3A4, CYP2C9 and is a potential inducer of CYP2C19. Concentrations of pantoprazole may decrease due to induction of CYP3A4. Consider monitoring of pantoprazole efficacy.

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. Dabrafenib does not interact with this elimination pathway. 

Coadministration has not been studied. Paracetamol is mainly metabolised by glucuronidation (via UGTs 1A9 (major), 1A6, 1A1, and 2B15), sulfation, and to a lesser extent, by oxidation (CYPs 2E1 (major), 1A2, 3A4 and 2D6). Dabrafenib is an inducer of CYP3A4 and potentially induces UGT, and may decrease concentrations of paracetamol. Monitoring of paracetamol efficacy is recommended.

Coadministration has not been studied. Paroxetine is mainly metabolised by CYP2D6 and CYP3A4. Dabrafenib is an inducer of CYP3A4 and may decrease concentrations of paroxetine. Monitoring of paroxetine efficacy is recommended. Monitoring of paroxetine plasma concentrations should be considered, if available.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. However, coadministration may increase risk of neutropenia, fatigue, and thrombocytopenia. Due to the risk of additive haematological toxicity, haematological parameters should be monitored if coadministered with trametinib plus dabrafenib.

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). Dabrafenib does not interfere with the elimination of penicillins.

Coadministration has not been studied. Perazine is metabolised mainly by CYPs 1A2, 3A4 and 2C19 and to a lesser extent by CYPs 2C9, 2D6 and 2E1, with oxidation via FMO3. Dabrafenib is an inducer of CYP3A4, CYP2C9 and possibly CYP2C19. Therefore, dabrafenib may decrease the plasma exposure of perazine. Monitoring for perazine efficacy is recommended when dabrafenib is coadministered with perazine. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. The metabolism of periciazine has not been well characterised but is likely to involve CYP2D6. Dabrafenib does not inhibit or induce CYP2D6.

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. Dabrafenib is an inducer of CYP3A4 and may increase biotransformation to active substance. Monitoring of blood pressure is recommended. 

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Perphenazine is metabolised by CYP2D6. Dabrafenib does not inhibit or induce CYP2D6. No clinically relevant QTc prolonging effects were observed after administration of dabrafenib (300 mg twice daily, two times the recommended dose). However, the incidences of QTc ≥501 msec and QTc increase of >60 msec from baseline were significantly higher with the combination dabrafenib-trametinib (4% and 13%, respectively) compared with trametinib (2% and 3%, respectively) and dabrafenib (<1% and 3%, respectively) monotherapies. Therefore, caution is needed when trametinib and dabrafenib are used concomitantly and are co-administered with a drug with a known risk of Torsade de Pointes. If coadministration with perphenazine is necessary, close monitoring including ECG assessment is recommended.

Coadministration has not been studied. Pethidine is metabolised mainly by CYP2B6 and to a lesser extent by CYP3A4. Dabrafenib is a strong inducer of CYP3A4 and a potential inducer of CYP2B6. Concentrations of pethidine may decrease due to induction of CYP3A4 and CYP2B6. Monitoring of pethidine efficacy is recommended. 

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 by acetylation. Dabrafenib does not interfere with these metabolic pathways.

Coadministration has not been studied but should be avoided. Phenobarbital is metabolised in the liver by CYP2C19 and CYP2C9 and to a lesser extent by CYP2E1. Dabrafenib is an inducer of CYP2C19 and CYP2C9 and may decrease concentrations of phenobarbital. Dose adjustments for phenobarbital should be considered. Monitor plasma concentrations, if available. Furthermore, phenobarbital is an inducer of CYP3A4 and may significantly decrease concentrations of dabrafenib. Decreased dabrafenib exposure can lead to decreased efficacy. Selection of an alternative concomitant medication with no or minimal enzyme induction potential is recommended. If coadministration is clinically necessary, consider monitoring of dabrafenib efficacy and plasma concentrations, if available. Increasing the dose of dabrafenib when co-administering with moderate or strong CYP3A inducers has not been studied and no formal dose advice can be given.

Coadministration has not been studied. Phenprocoumon is mainly metabolised by CYP2C9 and CYP3A4. Dabrafenib is an inducer of CYP3A4, CYP2C9 and is a potential inducer of CYP2C19. Concentrations of phenprocoumon may decrease due to induction of CYP3A4 and CYP2C9. Close monitoring of INR is recommended.

Coadministration has not been studied but should be avoided. Phenytoin is mainly metabolised by CYP2C9 and to a lesser extent by CYP2C19. Dabrafenib is an inducer of CYP2C9 and possibly of CYP2C19, and concentrations of phenytoin may decrease. If coadministration is unavoidable, monitor closely for phenytoin efficacy. Dose increments should be considered. Monitor phenytoin plasma concentrations, if available. Furthermore, phenytoin is a potent inducer of CYP3A4, UGT and P-gp. Concentrations of dabrafenib may decrease due to induction of CYP3A4. For one individual within a study (BRF113220) of patients with BRAF mutant metastatic melanoma, coadministration of dabrafenib (repeat doses of 150 mg twice daily) and phenytoin (300 mg twice daily) decreased dabrafenib AUC and Cmax by 62% and 77%, respectively. Hydroxy-dabrafenib and desmethyl-dabrafenib AUC and Cmax also decreased by 31% and 61%, and 63% and 73%, respectively.  Therefore, coadministration is not recommended, since a decrease in exposure can lead to decreased efficacy. Selection of an alternative concomitant medication with no or minimal enzyme or transporter induction potential is recommended. Increasing the dose of dabrafenib when coadministering with moderate or strong CYP3A inducers has not been studied therefore no formal dose advice can be given.

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. Dabrafenib does not inhibit or induce CYP4F2.

Coadministration has not been studied but is contraindicated. Pimozide is mainly metabolised by CYP3A4 and to a lesser extent by CYP2D6. Dabrafenib is an inducer of CYP3A4 and may decrease pimozide concentrations. Monitoring of pimozide efficacy is recommended. The product labels for pimozide contraindicate its use in the presence of other drugs that prolong the QT interval, such as dabrafenib coadministered with trametinib. The incidences of QTc ≥501 msec and of QTc increase of >60 msec from baseline were significantly higher with the combination dabrafenib-trametinib (4% and 13%, respectively) compared with the trametinib (2% and 3%, respectively) and the dabrafenib (<1% and 3%, respectively) monotherapy populations.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pindolol is partly metabolised to hydroxymetabolites (possibly via CYP2D6) and partly eliminated unchanged in the urine. Dabrafenib does not interfere with this metabolic or elimination pathway.

Coadministration has not been studied. Pioglitazone is metabolised mainly by CYP2C8 and to a lesser extent by CYPs 3A4, 1A2 and 2C9. Dabrafenib is an inducer of CYP3A4, CYP2C9 and is a potential inducer of CYP2C8. Concentrations of pioglitazone may decrease due to induction of CYP3A4 and CYP2C9. Monitoring of blood glucose levels is recommended.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. The metabolism of pipotiazine has not been well described but may involve CYP2D6. Dabrafenib does not inhibit or induce CYP2D6. No clinically relevant QTc prolonging effects were observed after administration of dabrafenib (300 mg twice daily, two times the recommended dose). However, the incidences of QTc ≥501 msec and QTc increase of >60 msec from baseline were significantly higher with the combination dabrafenib-trametinib (4% and 13%, respectively) compared with trametinib (2% and 3%, respectively) and dabrafenib (<1% and 3%, respectively) monotherapies. Therefore, caution is needed when trametinib and dabrafenib are used concomitantly and are co-administered with a drug with a known risk of Torsade de Pointes. If coadministration with pipotiazine is necessary, close monitoring including ECG assessment is recommended.

Coadministration has not been studied. Piroxicam is primarily metabolised by CYP2C9. Dabrafenib is an inducer of CYP2C9 and may decrease concentrations of piroxicam. Monitoring of piroxicam efficacy is recommended. 

Coadministration has not been studied. Pitavastatin is metabolised by UGT1A3 and UGT2B7 with minimal metabolism by CYP2C9 and CYP2C8. Dabrafenib is an inducer of CYP2C9 and is a potential inducer of UGT and CYP2C8. Concentrations of pitavastatin may decrease due to induction of CYP2C9, CYP2C8 and UGT. Monitoring of cholesterol concentrations is recommended and adjust dose accordingly.

Coadministration has not been studied. Posaconazole is metabolised by UGT. Dabrafenib is a potential inducer of UGT and may decrease concentrations of posaconazole. Monitoring of posaconazole efficacy is recommended. Monitor posaconazole concentrations, if available. Posaconazole is a strong inhibitor of CYP3A4 and may increase concentrations of dabrafenib. Concurrent use of CYP3A4 inhibitors should be avoided. Selection of an alternative concomitant medication with no or minimal enzyme inhibition potential is recommended. No clinically relevant QTc prolonging effects were observed after administration of dabrafenib (300 mg twice daily, two times the recommended dose). However, the incidences of QTc ≥501 msec and QTc increase of >60 msec from baseline were significantly higher with the combination dabrafenib-trametinib (4% and 13%, respectively) compared with trametinib (2% and 3%, respectively) and dabrafenib (<1% and 3%, respectively) monotherapies. Therefore, caution is needed when trametinib and dabrafenib are used concomitantly and are co-administered with a drug with a known risk of Torsade de Pointes. If coadministration with posaconazole is necessary, close monitoring including ECG assessment is recommended.

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

Coadministration has not been studied. Prasugrel is a prodrug and is converted to its active metabolite mainly by CYP3A4 and CYP2B6. Dabrafenib is an inducer of CYP3A4 and is a potential inducer of CYP2B6. Concentrations of prasugrel may decrease but concentrations of the active metabolite may increase due to induction of CYP3A4. Coadministration is not recommended due to the increased risk of bleeding. If coadministration is necessary, close monitoring for bleeding is recommended.

Coadministration has not been studied. Pravastatin is metabolised by CYP3A4 and is a substrate of OATP1B1. Dabrafenib is an inducer of OATP1B1, but a clinically relevant interaction is unlikely. Dabrafenib is also an inducer of CYP3A4 and may decrease pravastatin concentrations. Monitoring of cholesterol concentrations is recommended and adjust dose accordingly.

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. Dabrafenib does not interact with this metabolic pathway.

Coadministration has not been studied. Prednisolone undergoes hepatic metabolism via CYP3A4. Dabrafenib is an inducer of CYP3A4 and may decrease prednisolone exposure. Since prednisolone has a wide therapeutic index, this is unlikely to be of clinical significance but monitoring of prednisolone efficacy may be required.

Coadministration has not been studied. Prednisone is converted to the active metabolite prednisolone by 11-B-hydroxydehydrogenase. Prednisolone is then metabolised by CYP3A4. Dabrafenib is an inducer of CYP3A4 and may decrease prednisolone concentrations. Since prednisolone has a wide therapeutic index, this is unlikely to be of clinical significance but monitoring of prednisolone efficacy may be required.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pregabalin is cleared mainly by glomerular filtration. Dabrafenib does not interfere with this elimination pathway.

Coadministration has not been studied. Prochlorperazine is metabolised by CYP2D6 and CYP2C19. Dabrafenib is a potential inducer of CYP2C19 and may decrease prochlorperazine concentrations. Monitoring of prochlorperazine efficacy is recommended. No clinically relevant QTc prolonging effects were observed after administration of dabrafenib (300 mg twice daily, two times the recommended dose). However, the incidences of QTc ≥501 msec and QTc increase of >60 msec from baseline were significantly higher with the combination dabrafenib-trametinib (4% and 13%, respectively) compared with trametinib (2% and 3%, respectively) and dabrafenib (<1% and 3%, respectively) monotherapies. Therefore, caution is needed when trametinib and dabrafenib are used concomitantly and are co-administered with a drug with a known risk of Torsade de Pointes. If coadministration with prochlorperazine is necessary, close monitoring including ECG assessment is recommended.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Promethazine is metabolised by CYP2D6. Dabrafenib does not inhibit or induce CYP2D6. No clinically relevant QTc prolonging effects were observed after administration of dabrafenib (300 mg twice daily, two times the recommended dose). However, the incidences of QTc ≥501 msec and QTc increase of >60 msec from baseline were significantly higher with the combination dabrafenib-trametinib (4% and 13%, respectively) compared with trametinib (2% and 3%, respectively) and dabrafenib (<1% and 3%, respectively) monotherapies. Therefore, caution is needed when trametinib and dabrafenib are used concomitantly and are co-administered with a drug with a known risk of Torsade de Pointes. If coadministration with promethazine is necessary, close monitoring including ECG assessment is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Propafenone is metabolised mainly by CYP2D6 and to a lesser extent by CYP1A2 and CYP3A4. Dabrafenib is an inducer of CYP3A4 and may decrease concentrations of propafenone. Since CYP3A4 mediated metabolism is a minor pathway, a clinically relevant interaction is unlikely. 

Coadministration has not been studied. Propranolol is metabolised by 3 routes (aromatic hydroxylation by CYP2D6, N-dealkylation followed by side chain hydroxylation via CYPs 1A2, 2C19, 2D6, and direct glucuronidation). Dabrafenib is a potential inducer of CYP2C19 and UGT and may decrease concentrations of propranolol. As the clinical relevance of this interaction is unknown, monitoring of blood pressure and heart rate 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 renally eliminated, 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. Dabrafenib 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. Dabrafenib is an inducer of CYP3A4 and may decrease quetiapine concentrations. Monitoring of quetiapine efficacy 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. Dabrafenib is an inhibitor of OAT3 in vitro, but a clinically relevant interaction is unlikely. 

Coadministration has not been studied. Quinidine is a substrate of CYP3A4 and an inhibitor of CYP2D6. Dabrafenib is an inducer of CYP3A4 and may decrease concentrations of quinidine. Due to the narrow therapeutic index of quinidine dose increments should be considered and monitoring of quinidine efficacy is recommended. Monitoring quinidine plasma concentrations should be considered, if available. No clinically relevant QTc prolonging effects were observed after administration of dabrafenib (300 mg twice daily, two times the recommended dose). However, the incidences of QTc ≥501 msec and QTc increase of >60 msec from baseline were significantly higher with the combination dabrafenib-trametinib (4% and 13%, respectively) compared with trametinib (2% and 3%, respectively) and dabrafenib (<1% and 3%, respectively) monotherapies. Therefore, caution is needed when trametinib and dabrafenib are used concomitantly and are co-administered with a drug with a known risk of Torsade de Pointes. If coadministration with quinidine is necessary, close monitoring including ECG assessment is recommended.

The aqueous solubility of dabrafenib is pH dependent with only a low solubility at pH 1. In patients with BRAF V600 mutation positive tumours, coadministration of dabrafenib (150 mg twice daily) and rabeprazole (40 mg once daily) increased dabrafenib AUC by 3% and decreased dabrafenib Cmax by 12%. However, rabeprazole is mainly metabolised via non-enzymatic reduction and to a lesser extent by CYP2C19 and CYP3A4. Dabrafenib is an inducer of CYP3A4 and is a potential inducer of CYP2C19. Concentrations of rabeprazole may decrease due to induction of CYP3A4. Consider monitoring of rabeprazole efficacy.

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. Dabrafenib is an inducer of CYP3A4 and may increase biotransformation to active substance. As the clinical relevance of this interaction is unknown, monitoring of blood pressure is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. The aqueous solubility of dabrafenib is pH dependent with only a low solubility at pH 1. Coadministration of dabrafenib (150 mg twice daily) and rabeprazole (40 mg once daily) increased dabrafenib AUC by 3% and decreased dabrafenib Cmax by 12%. Furthermore, ranitidine is excreted via OAT1/OAT3. Dabrafenib is an inhibitor of OAT1/3 in vitro but a clinically relevant interaction is unlikely.

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. Furthermore, ranolazine is a weak inhibitor of P-gp, CYP3A4 and CYP2D6. Concentrations of dabrafenib may increase due to inhibition of CYP3A4. Dabrafenib is an inducer of CYP3A4 and P-gp and may decrease concentrations of ranolazine. Monitoring for dabrafenib toxicity and ranolazine efficacy is recommended. No clinically relevant QTc prolonging effects were observed after administration of dabrafenib (300 mg twice daily, two times the recommended dose). However, the incidences of QTc ≥501 msec and QTc increase of >60 msec from baseline were significantly higher with the combination dabrafenib-trametinib (4% and 13%, respectively) compared with trametinib (2% and 3%, respectively) and dabrafenib (<1% and 3%, respectively) monotherapies. Therefore, caution is needed when trametinib and dabrafenib are used concomitantly and are co-administered with a drug with a known risk of Torsade de Pointes. If coadministration is necessary, close monitoring including ECG assessment is recommended.

Coadministration has not been studied. Reboxetine is metabolised by CYP3A4. Dabrafenib is an inducer of CYP3A4 and may decrease concentrations of reboxetine. Monitoring of reboxetine plasma concentrations should be considered, if available. In vitro data indicate reboxetine to be a weak inhibitor of CYP3A4 but no effect on dabrafenib is expected as in vivo data showed no inhibitory effect on CYP3A4. 

Coadministration has not been studied. Repaglinide is metabolised by CYP2C8 and CYP3A4 with clinical data indicating it is a substrate of the hepatic transporter OATP1B1. Dabrafenib is an inducer of CYP3A4 and is a potential inducer of CYP2C8 and OATP1B1. Concentrations of repaglinide may decrease due to induction of CYP3A4. Monitoring of blood glucose levels is recommended. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Vitamin A esters are hydrolysed by pancreatic enzymes to retinol, which is then absorbed and re-esterified. Some retinol is stored in the liver but retinol not stored in the liver undergoes glucuronide conjugation and subsequent oxidation to retinal and retinoic acid. Dabrafenib 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. Rifabutin is metabolised by CYP3A and via deacetylation. Dabrafenib is an inducer of CYP3A4 and may decrease concentrations of rifabutin. As the clinical relevance of this interaction is unknown, monitoring of rifabutin efficacy may be required. Rifabutin is a strong inducer of CYP3A4 and may significantly decrease concentrations of dabrafenib. A decrease in dabrafenib exposure can lead to decreased efficacy. Selection of an alternative concomitant medication with no or minimal enzyme induction potential is recommended. If coadministration is clinically necessary, monitor dabrafenib plasma concentrations, if available. Increasing the dose of dabrafenib when coadministering with moderate or strong CYP3A4 inducers has not been studied and no formal dose advice can be given.

Coadministration has not been studied but should be avoided. Rifampicin is metabolised via deacetylation. Dabrafenib is unlikely to interfere with this pathway. However, rifampicin is a strong inducer of CYP3A4 and may significantly decrease concentrations of dabrafenib. A decrease in dabrafenib exposure can lead to decreased efficacy. Selection of an alternative concomitant medication with no or minimal enzyme induction potential is recommended. If coadministration is clinically necessary, monitor dabrafenib plasma concentrations, if available. Increasing the dose of dabrafenib when coadministering with moderate or strong CYP3A4 inducers has not been studied and no formal dose advice can be given.

Coadministration has not been studied but should be avoided. Rifapentine is metabolised via deacetylation. Dabrafenib is unlikely to interfere with this pathway. However, rifapentine is a strong inducer of CYP3A4 and CYP2C8, and may significantly decrease concentrations of dabrafenib. A decrease in dabrafenib exposure can lead to decreased efficacy. Selection of an alternative concomitant medication with no or minimal enzyme induction potential is recommended. If coadministration is clinically necessary, monitor dabrafenib plasma concentrations, if available. Increasing the dose of dabrafenib when coadministering with moderate or strong CYP3A4 and CYP2C8 inducers has not been studied and no formal dose advice can be given.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Rifaximin is mainly excreted in the faeces, almost entirely as unchanged drug. Dabrafenib does not interact with this elimination 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. Dabrafenib is an inducer of CYP3A4 and P-gp and may decrease risperidone concentrations. As the clinical relevance of this interaction is unknown, 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). Dabrafenib is an inducer of CYP3A4 (strong) and P-gp (in vitro) and may decrease concentrations of rivaroxaban. Monitoring of anti-Xa levels may be necessary.

Coadministration has not been studied. Rosiglitazone is metabolised mainly by CYP2C8 and to a lesser extent by CYP2C9. Dabrafenib is an inducer of CYP2C9 and is a potential inducer of CYP2C8. Concentrations of rosiglitazone may decrease due to induction of CYP2C9. Monitoring of blood glucose levels is recommended.

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. Dabrafenib is an inducer of OATP1B1, but a clinically relevant interaction is unlikely. 

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. Dabrafenib does not interact with this metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Salmeterol is metabolised by CYP3A4. Dabrafenib is an inducer of CYP3A4 and may decrease salmeterol concentrations. However, the systemic absorption of salmeterol after bronchial administration is low and a clinically relevant interaction via CYP3A4 induction is unlikely.

Coadministration has not been studied. Saxagliptin is mainly metabolised by CYP3A4 and is a substrate of P-gp. Dabrafenib induces CYP3A4 and P-gp. Concentrations of saxagliptin may decrease due to induction of CYP3A4. Monitoring of blood glucose levels is recommended.

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. Dabrafenib does not interfere with this pathway.

Coadministration has not been studied but is contraindicated. Sertindole is metabolised by CYP2D6 and CYP3A4. Dabrafenib is an inducer of CYP3A4 and may decrease sertindole concentrations. Monitoring of sertindole efficacy is recommended. The product labels for sertindole contraindicate its use in the presence of other drugs that prolong the QT interval, such as dabrafenib coadministered with trametinib. The incidences of QTc ≥501 msec and of QTc increase of >60 msec from baseline were significantly higher with the combination dabrafenib-trametinib (4% and 13%, respectively) compared with the trametinib (2% and 3%, respectively) and the dabrafenib (<1% and 3%, respectively) monotherapy populations. 

Coadministration has not been studied. Sertraline is mainly metabolised by CYP2B6 and to a lesser extent by CYPs 2C9, 2C19, 2D6 and 3A4. Dabrafenib is an inducer of CYP3A4, CYP2C9 and is a potential inducer of CYP2C19 and CYP2B6. Concentrations of sertraline may decrease due to induction of CYP3A4 and CYP2C9. Monitoring of sertraline efficacy is recommended. Monitoring of sertraline plasma concentrations should be considered, if available. 

Coadministration has not been studied. Sildenafil is metabolised mainly by CYP3A4 and to a lesser extent by CYP2C9. Dabrafenib is an inducer of CYP3A4 and CYP2C9, and may decrease concentrations of sildenafil. Monitoring of blood pressure is recommended.

Coadministration has not been studied. Simvastatin is metabolised by CYP3A4 and the metabolite is a substrate of OATP1B1. Dabrafenib is an inducer of OATP1B1, but a clinically relevant interaction is unlikely. Dabrafenib is also an inducer of CYP3A4 and may decrease simvastatin concentrations. Monitoring for cholesterol concentrations is recommended and adjust dose accordingly.

Coadministration has not been studied. Sirolimus is metabolised by CYP3A4 and is a substrate of P-gp. Dabrafenib is an inducer of P-gp, but a clinically relevant interaction is unlikely. Dabrafenib is also an inducer of CYP3A4 and may decrease concentrations of sirolimus. Monitoring of sirolimus plasma concentrations is recommended, if available. Coadministration may also increase the risk of neutropenia, fatigue, and thrombocytopenia. Due to the risk of additive haematological toxicity, haematological parameters should be monitored if coadministered with trametinib plus dabrafenib.

Coadministration has not been studied. Sitagliptin is primarily eliminated in the urine as unchanged drug (active secretion by OAT3, OATP4C1, and P-gp) and metabolism by CYP3A4 represents a minor elimination pathway. Although dabrafenib is an inducer of P-gp, the risk of a clinically significant interaction is unlikely. Dabrafenib is also an inducer of CYP3A4 and may decrease concentrations of sitagliptin. Since CYP3A4 mediated metabolism is only a minor pathway, this is unlikely to be of clinical significance.

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 dabrafenib or to be affected if co-administered with dabrafenib. 

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Sotalol is excreted unchanged via renal elimination. Dabrafenib does not interact with this elimination pathway. However, the product labels for sotalol advises extreme caution if given with other drugs that prolong the QT interval, such as dabrafenib coadministered with trametinib. The incidences of QTc ≥501 msec and of QTc increase of >60 msec from baseline were significantly higher with the combination dabrafenib-trametinib (4% and 13%, respectively) compared with the trametinib (2% and 3%, respectively) and the dabrafenib (<1% and 3%, respectively) monotherapy populations. 

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. Dabrafenib does not interact with this elimination 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. Dabrafenib does not interfere with this metabolic pathway. 

Coadministration has not been studied. Stanozolol undergoes hepatic metabolism. Dabrafenib is an inducer of CYP3A4, CYP2C9 and a potential inducer of CYPs 2C8, 2C19 and 2B6. Concentrations of stanozolol may decrease due to induction of CYP3A4 and CYP2C9. Since stanozolol has a wide therapeutic index, this is unlikely to be of clinical significance but monitoring of stanozolol efficacy may be required.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Like other proteins, streptokinase is metabolised proteolytically in the liver and eliminated via the kidneys. Dabrafenib does not interfere with this pathway. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Streptomycin is eliminated by glomerular filtration. Dabrafenib does not interfere with this elimination pathway.

Coadministration has not been studied. In vitro studies suggest a role of CYP2C9 in sulfadiazine metabolism. Dabrafenib is an inducer of CYP2C9 and may decrease concentrations of sulfadiazine. As the clinical relevance of this interaction is unknown, monitoring of sulfadiazine efficacy should be considered.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Sulpiride is mainly excreted in the urine and faeces as unchanged drug. Dabrafenib does not interact with this elimination pathway. No clinically relevant QTc prolonging effects were observed after administration of dabrafenib (300 mg twice daily, two times the recommended dose). However, the incidences of QTc ≥501 msec and QTc increase of >60 msec from baseline were significantly higher with the combination dabrafenib-trametinib (4% and 13%, respectively) compared with trametinib (2% and 3%, respectively) and dabrafenib (<1% and 3%, respectively) monotherapies. Therefore, caution is needed when trametinib and dabrafenib are used concomitantly and are co-administered with a drug with a known risk of Torsade de Pointes. If coadministration with sulpiride is necessary, close monitoring including ECG assessment is recommended.

Tacrolimus is an inhibitor of CYP3A4 and OATP1B1 in vitro but produced modest inhibition of CYP3A4 and OATP1B1 in the range of clinical concentrations. Tacrolimus could potentially increase dabrafenib concentrations although only to a modest extent. No a priori dosage adjustment of dabrafenib is recommended. Tacrolimus is metabolised by CYP3A4. Dabrafenib is an inducer of CYP3A4 and may decrease concentrations of tacrolimus. In a single case report, coadministration of dabrafenib and tacrolimus resulted in a decreased tacrolimus exposure. If coadministration is unavoidable, monitor plasma concentrations of tacrolimus very closely and adjust dose if necessary during initiation and discontinuation of dabrafenib. No clinically relevant QTc prolonging effects were observed after administration of dabrafenib (300 mg twice daily, two times the recommended dose). However, the incidences of QTc ≥501 msec and QTc increase of >60 msec from baseline were significantly higher with the combination dabrafenib-trametinib (4% and 13%, respectively) compared with trametinib (2% and 3%, respectively) and dabrafenib (<1% and 3%, respectively) monotherapies. Therefore, caution is needed when trametinib and dabrafenib are used concomitantly and are co-administered with a drug with a known risk of Torsade de Pointes. If coadministration with tacrolimus is necessary, close monitoring including ECG assessment is recommended.

Coadministration has not been studied. Tadalafil is metabolised by CYP3A4. Dabrafenib is an inducer of CYP3A4 and may decrease tadalafil concentrations. Monitoring of blood pressure is recommended.

Coadministration has not been studied. Tamsulosin is metabolised mainly by CYP3A4 and to a lesser extent by CYP2D6. Dabrafenib is an inducer of CYP3A4 and may decrease tamsulosin concentrations. Although tamsulosin has a wide therapeutic index, monitoring of efficacy may be required.

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. Dabrafenib does not interact with this elimination pathway.

Coadministration has not been studied. Telithromycin is an inhibitor of CYP3A4 and may increase concentrations of dabrafenib. Concurrent use of CYP3A4 inhibitors should be avoided. Selection of an alternative concomitant medication with no or minimal enzyme inhibition potential is recommended. If coadministration is unavoidable, close monitoring for dabrafenib toxicity is recommended and consider monitoring of dabrafenib plasma concentrations, if available.

Coadministration has not been studied. Telmisartan is mainly glucuronidated by UGT1A3. Dabrafenib is a potential inducer of UGT and may decrease telmisartan concentrations. Monitoring of blood pressure is recommended. 

Coadministration has not been studied. Temazepam is mainly glucuronidated. Dabrafenib is a potential inducer of UGT and may decrease concentrations of temazepam. However, since temazepam does not have a narrow therapeutic index, this is unlikely to be clinically relevant but consider monitoring of temazepam efficacy.

Coadministration has not been studied. Terbinafine is metabolised by CYPs 1A2, 2C9, 3A4 and to a lesser extent by CYPs 2C8 and 2C19. Dabrafenib is an inducer of CYP3A4, CYP2C9 and is a potential inducer of CYP2C8 and CYP2C19. Concentrations of terbinafine may decrease due to induction of CYP3A4 and CYP2C9. Monitoring of terbinafine efficacy is recommended. 

Coadministration has not been studied. Testosterone is metabolised by CYP3A4. Dabrafenib is an inducer of CYP3A4 and may decrease testosterone concentrations. Since testosterone has a wide therapeutic index, this is unlikely to be of clinical significance but monitoring of testosterone efficacy may be required.

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. Dabrafenib does not interact with this elimination pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Theophylline is mainly metabolised by CYP1A2. Dabrafenib 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 but is contraindicated. Thioridazine is metabolised by CYP2D6, and to a lesser extent by CYP3A4. Dabrafenib is an inducer of CYP3A4. Since CYP3A4 is a minor pathway, a clinically relevant interaction is unlikely. However, the product labels for thioridazine contraindicate its use in the presence of other drugs that prolong the QT interval, such as dabrafenib coadministered with trametinib. The incidences of QTc ≥501 msec and of QTc increase of >60 msec from baseline were significantly higher with the combination dabrafenib-trametinib (4% and 13%, respectively) compared with the trametinib (2% and 3%, respectively) and the dabrafenib (<1% and 3%, respectively) monotherapy populations.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Tiapride is excreted largely unchanged in urine. Dabrafenib does not interfere with this elimination pathway. No clinically relevant QTc prolonging effects were observed after administration of dabrafenib (300 mg twice daily, two times the recommended dose). However, the incidences of QTc ≥501 msec and QTc increase of >60 msec from baseline were significantly higher with the combination dabrafenib-trametinib (4% and 13%, respectively) compared with trametinib (2% and 3%, respectively) and dabrafenib (<1% and 3%, respectively) monotherapies. Therefore, caution is needed when trametinib and dabrafenib are used concomitantly and are co-administered with a drug with a known risk of Torsade de Pointes. If coadministration with tiapride is necessary, close monitoring including ECG assessment is recommended.

Coadministration has not been studied. Ticagrelor is a substrate and mild inhibitor of CYP3A4. Dabrafenib is an inducer of CYP3A4 and may decrease concentrations of ticagrelor. Furthermore, concentrations of dabrafenib may slightly increase due to inhibition of CYP3A4 by ticagrelor. As the clinical relevance of these interactions is unknown, monitoring of ticagrelor efficacy and dabrafenib toxicity is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Systemic absorption of timolol after ocular administration is low but absorbed timolol is predominantly metabolised in the liver by CYP2D6. Dabrafenib does not inhibit or induce CYP2D6.  

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. Dabrafenib does not interact with this elimination pathway.

Coadministration has not been studied. Tolbutamide is mainly metabolised by CYP2C9 and to a lesser extent by CYP2C8 and CYP2C19. Dabrafenib is an inducer of CYP2C9 and is a potential inducer of CYP2C8 and CYP2C19. Concentrations of tolbutamide may decrease due to induction of CYP2C9. Monitoring of blood glucose levels is recommended.