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. Venetoclax 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. Venetoclax does not inhibit or induce CYPs. However, in healthy volunteers (n=3), coadministration of venetoclax (400 mg single dose) and warfarin (5 mg single dose), increased AUC and Cmax of R-warfarin and S-warfarin by 18-28%. Therefore it is recommended to monitor the INR closely if venetoclax is coadministered with acenocoumarol.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Agomelatine is metabolised predominantly via CYP1A2 (90%), with a small proportion metabolised by CYP2C9 and CYP2C19 (10%). Venetoclax does not inhibit or induce CYPs.

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 but based on metabolism and clearance a clinically significant interaction is unlikely. Alfentanil undergoes extensive CYP3A4 metabolism. Venetoclax does not inhibit or induce CYPs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Alfuzosin is metabolised by CYP3A. Venetoclax does not inhibit or induce CYPs. 

Coadministration has not been studied. Aliskiren is minimally metabolised and is mainly excreted unchanged in faeces. However, P-gp is a major determinant of aliskiren bioavailability. Venetoclax may inhibit intestinal P-gp and BCRP at therapeutic doses. In healthy volunteers, coadministration of venetoclax (100 mg single dose) and the P-gp substrate, digoxin (0.5 mg single dose), increased digoxin AUC and Cmax by 9% and 35%, respectively. A similar effect may occur with aliskiren. If coadministration is unavoidable, separate aliskiren administration from venetoclax administration as much as possible to minimise a potential interaction. Close monitoring for aliskiren toxicity is recommended.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. In vitro data indicate that alosetron is metabolised by CYPs 2C9, 3A4 and 1A2. Venetoclax does not inhibit or induce CYPs. 

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. The solubility of venetoclax is extremely low over the whole pH range. Given that venetoclax is to be administered with food, at a state with somewhat increased gastric pH and where solubilising agents in the food and gastric fluids are likely to increase bioavailability, acid-reducing agents are not expected to affect venetoclax bioavailability.

Coadministration has not been studied. Ambrisentan is metabolised by glucuronidation via UGTs 1A3, 1A9 and 2B7 and to a lesser extent by CYP3A4 and CYP2C19. Ambrisentan is also a substrate of P-gp. Venetoclax may inhibit intestinal P-gp at therapeutic doses. In healthy volunteers, coadministration of venetoclax (100 mg single dose) and the P-gp substrate, digoxin (0.5 mg single dose), increased digoxin AUC and Cmax by 9% and 35%, respectively. A similar effect may occur after coadministration with ambrisentan. Monitoring for signs and symptoms of increased exposure to ambrisentan should be considered.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amikacin is eliminated by glomerular filtration. Venetoclax does not interact 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. Venetoclax is unlikely to affect the elimination of amiloride.

Coadministration has not been studied but should be avoided. Amiodarone is metabolised by CYP2C8 and CYP3A4. Venetoclax does not inhibit or induce CYPs. Moreover, the major metabolite of amiodarone, desethylamiodarone, is an inhibitor of CYPs 3A4 (weak), 2C9 (moderate), 2D6 (moderate), 2C19 (weak), 1A1 (strong) and 2B6 (moderate) and P-gp (strong). Concentrations of venetoclax may increase due to weak CYP3A4 inhibition and strong P-gp inhibition. Model simulations indicated no effect of weak CYP3A inhibitors on venetoclax Cmax or AUC. No clinically significant interaction is expected. However, coadministration of a 600 mg single dose of rifampicin, a P-gp inhibitor, increased venetoclax Cmax by 106% and AUC by 78%. Coadministration of venetoclax and amiodarone at initiation and during the titration phase should be avoided. If coadministration is clinically necessary, reduce venetoclax dose by at least 50%. Monitor closely for signs of toxicities. The venetoclax dose that was used prior should be resumed 2 to 3 days after discontinuation of amiodarone. 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). Venetoclax is unlikely to significantly affect amisulpride elimination. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amitriptyline is metabolised predominantly by CYP2D6 and CYP2C19, with a small proportion metabolised by CYPs 3A4, 1A2 and 2C9. Venetoclax does not inhibit or induce CYPs.

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

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. Venetoclax is unlikely to interfere with this elimination pathway.

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. Venetoclax does not interfere with this 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 and so monitoring may be required.

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. Venetoclax 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. Venetoclax does not interfere with this elimination pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. The solubility of venetoclax is extremely low over the whole pH range. Given that venetoclax is to be administered with food, at a state with somewhat increased gastric pH and where solubilising agents in the food and gastric fluids are likely to increase bioavailability, acid-reducing agents are not expected to affect venetoclax bioavailability.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Apixaban is metabolised by CYP3A4 and to a lesser extent by CYPs 1A2, 2C8, 2C9 and 2C19. Venetoclax does not inhibit or induce CYPs. 

Coadministration has not been studied but should be approached with caution. Aprepitant is mainly metabolised by CYP3A4 and to a lesser extent by CYP1A2 and CYP2C19. Venetoclax does not inhibit or induce CYPs. However, during treatment aprepitant is a moderate inhibitor of CYP3A4 and may increase concentrations of venetoclax during the three days of coadministration. Therefore, coadministration should be avoided during the initiation and dose-titration phase to minimise the risk of tumour lysis syndrome. Selection of an alternate concomitant medicinal product with no or minimal potential to inhibit CYP3A4 should be considered. If coadministration is unavoidable, reduce the venetoclax dose by at least 50% during the initiation, titration phase and steady daily dose. Close monitoring for signs and symptoms of tumor lysis syndrome is recommended. Furthermore, after treatment aprepitant is a weak inducer of CYP3A4, CYP2C9 and UGT. Concentrations of venetoclax may decrease due to weak induction of CYP3A4, but this is not considered to be clinically not relevant.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Asenapine is metabolised by glucuronidation (UGT1A4) and oxidative metabolism (CYPs 1A2 (major), 3A4 and 2D6 (minor)). Venetoclax does not inhibit or induce UGTs or CYPs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Astemizole is metabolised by CYPs 2D6, 2J2 and 3A4. Venetoclax does not inhibit or induce CYPs.

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. Venetoclax does not interfere with this elimination pathway.

Coadministration has not been studied. Atorvastatin is metabolised by CYP3A4 and is a substrate of P-gp. Venetoclax may inhibit intestinal P-gp and BCRP at therapeutic doses. In healthy volunteers, coadministration of venetoclax (100 mg single dose) and the P-gp substrate, digoxin (0.5 mg single dose), increased digoxin AUC and Cmax by 9% and 35%, respectively. A similar effect may occur with atorvastatin. Furthermore, atorvastatin is a substrate of OATP1B1. Venetoclax is a weak inhibitor of OATP1B1 in vitro and may increase concentrations of atorvastatin. Due to both inhibition of P-gp and OATP, close monitoring of atorvastatin-related toxicity is recommended. It is also recommended to start with the lowest dose of atorvastatin and titrate up to the desired clinical effect while monitoring for safety.

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

Coadministration has not been studied. Azithromycin is mainly eliminated via biliary excretion with animal studies suggesting this may occur via P-gp and MRP2. Venetoclax may inhibit intestinal P-gp at therapeutic doses. The clinical relevance of this interaction is unknown. Close monitoring of azithromycin toxicity is recommended if azithromycin is administered orally. Furthermore, azithromycin is an inhibitor of P-gp and may increase venetoclax concentrations. In healthy volunteers (n=12), coadministration of venetoclax (200 mg single dose) and the P-gp inhibitor, rifampicin (600 mg single dose), increased venetoclax AUC and Cmax by 78% and 106%, respectively. Coadministration at initiation and during the titration phase should be avoided. If coadministration is necessary, the US product label recommends reducing the venetoclax dose by at least 50%. Monitor closely for signs of venetoclax toxicities. The venetoclax dose that was used prior to initiating azithromycin should be resumed 2 to 3 days after discontinuation of azithromycin.

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. Venetoclax does not interact with this pathway. 

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

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bepridil is metabolised by CYP2D6 (major) and CYP3A4. Venetoclax does not inhibit or induce CYPs. 

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

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. Venetoclax 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. Venetoclax 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. Venetoclax does not inhibit or induce CYPs. However, bisoprolol is also a substrate of P-gp. Venetoclax may inhibit intestinal P-gp and BCRP at therapeutic doses. In healthy volunteers, coadministration of venetoclax (100 mg single dose) and the P-gp substrate, digoxin (0.5 mg single dose), increased digoxin AUC and Cmax by 9% and 35%, respectively. A similar effect may occur with bisoprolol. Bisoprolol administration should be separated from venetoclax administration as much as possible to minimise a potential interaction. Close monitoring for bisoprolol toxicity is recommended.

Coadministration has not been studied. Bosentan is a substrate and inducer of CYP3A4 and CYP2C9 and could potentially decrease venetoclax exposure. In patients with PAH (n=69), coadministration of bosentan and a CYP3A4 substrate, imatinib, decreased imatinib concentrations by 33%. A similar result may occur with venetoclax. Furthermore, in healthy volunteers (n=10), coadministration of venetoclax (200 mg single dose) and the strong CYP3A4 inducer, rifampicin (600 mg once daily for 13 days), decreased venetoclax AUC and Cmax by 71% and 42%, respectively. Therefore, coadministration should be avoided. Selection of an alternate concomitant medicinal product, with no or minimal potential to induce CYP3A4 should be considered. Increasing the dose of venetoclax when co-administering with strong or moderate CYP3A inducers is unlikely to sufficiently compensate for the loss of exposure.

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

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Buprenorphine undergoes both N-dealkylation to form norbuprenorphine (via CYP3A4) and glucuronidation (via UGT2B7 and UGT1A1). Venetoclax does not inhibit or induce CYPs or UGTs.

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

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Calcium is eliminated through faeces, urine and sweat. Venetoclax does not interfere with these elimination pathways.

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. Venetoclax 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. Capreomycin is predominantly excreted via the kidneys as unchanged drug. Venetoclax 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. Venetoclax does not interfere with this elimination pathway.

Coadministration has not been studied but should be avoided. Carbamazepine is primarily metabolised by CYP3A4 and to a lesser extent by CYP2C8. Venetoclax does not inhibit or induce CYPs. However, carbamazepine is an inducer of CYPs 2C8 (strong), 2C9 (strong), 3A4 (strong), 1A2 (weak), 2B6 and UGT1A1. Concentrations of venetoclax may significantly decrease due to induction of CYP3A4. A decrease in exposure can lead to decreased efficacy. In healthy volunteers (n=10), coadministration of venetoclax (200 mg single dose) and the strong CYP3A4 inducer, rifampicin (600 mg once daily for 13 days), decreased venetoclax AUC and Cmax by 71% and 42%, respectively. A similar effect may occur with carbamazepine. Therefore, coadministration should be avoided. Selection of an alternate concomitant medicinal product, with no or minimal potential to induce CYP3A4 should be considered. Increasing the dose of venetoclax when coadministering with strong or moderate CYP3A inducers is unlikely to sufficiently compensate for the loss of exposure. 

Coadministration has not been studied. Carvedilol undergoes glucuronidation via UGTs 1A1, 2B4 and 2B7, and metabolism via CYP2D6 and to a lesser extent by CYPs 2C9 and 1A2. Venetoclax does not inhibit or induce UGTs or CYPs. However, carvedilol is also a substrate of P-gp. Venetoclax may inhibit intestinal P-gp and BCRP at therapeutic doses. In healthy volunteers, coadministration of venetoclax (100 mg single dose) and the P-gp substrate, digoxin (0.5 mg single dose), increased digoxin AUC and Cmax by 9% and 35%, respectively. A similar effect may occur with carvedilol. Carvedilol administration should be separated from venetoclax administration as much as possible to minimise a potential interaction. Close monitoring for carvedilol toxicity is recommended. Furthermore, carvedilol is an inhibitor of P-gp and may increase venetoclax concentrations. In healthy volunteers (n=12), coadministration of venetoclax (200 mg single dose) and the P-gp inhibitor, rifampicin (600 mg single dose), increased venetoclax AUC and Cmax by 78% and 106%, respectively. A similar effect may occur with carvedilol. Coadministration of venetoclax and carvedilol at initiation and during the titration phase should be avoided. If coadministration is necessary, the US product label recommends reducing the venetoclax dose by at least 50%. Monitor closely for signs of toxicities. The venetoclax dose that was used prior to initiating carvedilol should be resumed 2 to 3 days after discontinuation of carvedilol.

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. Venetoclax does not interact with this metabolic pathway. 

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

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. Venetoclax does not interfere with this elimination pathway.

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. Venetoclax 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. Venetoclax does not interfere with this elimination pathway.

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. Venetoclax 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. Venetoclax does not interfere with this elimination pathway.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cetirizine is only metabolised to a limited extent and is eliminated unchanged in the urine through both glomerular filtration and tubular secretion. In vitro data indicate that cetirizine inhibits OCT2. Venetoclax is unlikely to interact with the renal elimination of cetirizine.

Coadministration has not been studied. Chloramphenicol is predominantly glucuronidated. Venetoclax does not inhibit or induce UGTs. In vitro studies have shown that chloramphenicol is an inhibitor of CYP3A4 and may increase concentrations of venetoclax, thus increasing the risk of adverse events. Therefore, coadministration should be avoided during the initiation and dose-titration phase to minimize the risk of tumour lysis syndrome. Selection of an alternate concomitant medicinal product with no or minimal potential to inhibit CYP3A4 should be considered. If coadministration is unavoidable, reduce the venetoclax dose by at least 50% during the initiation, titration phase and steady daily dose. Close monitoring for signs and symptoms of tumor lysis syndrome is recommended. The venetoclax dose that was used prior to initiation of chloramphenicol should be resumed 2 to 3 days after discontinuation of chloramphenicol. Ocular use: Although chloramphenicol is systemically absorbed when used topically in the eye, the concentrations used are unlikely to cause a clinically significant interaction. 

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

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. Venetoclax does not inhibit or induce CYPs. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Chlorpromazine is metabolised mainly by CYP2D6, but also by CYP1A2. Venetoclax does not inhibit or induce CYPs. 

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. Venetoclax does not interact with this elimination pathway.

Coadministration has not been studied. Ciclosporin is a substrate of CYP3A4 and P-gp, and inhibits CYP3A4 and OATP1B1. Concentrations of venetoclax may increase due to moderate inhibition of CYP3A4. Therefore, coadministration of venetoclax and ciclosporin should be avoided at initiation and during the dose-titration phase to minimize the risk of tumour lysis syndrome. Selection of an alternate concomitant medicinal product with no or minimal potential to inhibit CYP3A4 should be considered. If coadministration is unavoidable, reduce the venetoclax dose by at least 50% during the initiation, titration phase and steady daily dose. Close monitoring for signs and symptoms of tumor lysis syndrome is recommended. The venetoclax dose that was used prior to initiation of ciclosporin should be resumed 2 to 3 days after discontinuation of ciclosporin. Furthermore, venetoclax may inhibit intestinal P-gp at therapeutic doses. In healthy volunteers, coadministration of venetoclax (100 mg single dose) and the P-gp substrate, digoxin (0.5 mg single dose), increased digoxin AUC and Cmax by 9% and 35%, respectively. Coadministration of P-gp substrates with a narrow therapeutic index is not recommended. Administration of ciclosporin should be separated from venetoclax administration as much as possible to minimise a potential interaction. Close monitoring for ciclosporin toxicity and blood concentrations 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. Venetoclax does not interfere with this elimination pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. In vitro data indicate that cimetidine is an inhibitor of OAT1 and OCT2 but at concentrations much higher than the observed clinical concentrations. Venetoclax does not interact with this pathway. Furthermore, the solubility of venetoclax is extremely low over the whole pH range. Given that venetoclax is to be administered with food, at a state with somewhat increased gastric pH and where solubilising agents in the food and gastric fluids are likely to increase bioavailability, acid-reducing agents are not expected to affect venetoclax bioavailability.

Coadministration has not been studied. Ciprofloxacin is primarily eliminated unchanged in the kidneys by glomerular filtration and tubular secretion via OAT3. Ciprofloxacin is also metabolised and partially cleared through the bile and intestine. Furthermore, ciprofloxacin is a weak to moderate inhibitor of CYP3A4 and a strong inhibitor of CYP1A2. Concentrations of venetoclax may increase due to moderate inhibition of CYP3A4. Therefore, coadministration should be avoided during the initiation and dose-titration phase to minimise the risk of tumour lysis syndrome. Selection of an alternate concomitant medicinal product with no or minimal potential to inhibit CYP3A4 should be considered. If coadministration is unavoidable, reduce the venetoclax dose by at least 50% during the initiation, titration phase and steady daily dose. Close monitoring for signs and symptoms of tumor lysis syndrome is recommended. The venetoclax dose that was used prior to initiation of ciprofloxacin should be resumed 2 to 3 days after discontinuation of ciprofloxacin.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cisapride is metabolised by CYP3A4. Venetoclax does not inhibit or induce CYPs. The solubility of venetoclax is extremely low over the whole pH range. Given that venetoclax is to be administered with food, at a state with somewhat increased gastric pH and where solubilising agents in the food and gastric fluids are likely to increase bioavailability, acid-reducing agents are not expected to affect venetoclax bioavailability.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Citalopram is metabolised by CYPs 2C19 (38%), 2D6 (31%) and 3A4 (31%). Venetoclax does not inhibit or induce CYPs.

Coadministration has not been studied but should be avoided. Clarithromycin is metabolised by CYP3A4. Venetoclax does not inhibit or induce CYPs. Clarithromycin is an inhibitor of CYP3A4 (strong) and P-gp and may increase concentrations of venetoclax. In patients with non-Hodgkin lymphoma (n=11), coadministration of venetoclax (50 mg single dose) and the strong CYP3A4 inhibitor, ketoconazole (400 mg once daily for 7 days), increased venetoclax AUC and Cmax by 6.4- and 2.3-fold, respectively. A similar effect may occur after coadministration with clarithromycin. Coadministration is contraindicated at initiation and during the dose-titration phase to minimise the risk of tumour lysis syndrome. Although coadministration should be avoided after completion of the dose titration phase, if coadministration is necessary for patients who are on a steady daily dose of venetoclax, reduce the venetoclax dose by at least 75%. Close monitoring for signs of toxicities and symptoms of tumor lysis syndrome is recommended. The venetoclax dose may need to be further adjusted. The venetoclax dose that was used prior to initiating the CYP3A inhibitor should be resumed 2 to 3 days after discontinuation of clarithromycin.

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. Venetoclax is unlikely to interact with this pathway.

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

Coadministration has not been studied but should be approached with caution. Clindamycin is metabolised by CYP3A4. Venetoclax does not inhibit or induce CYPs. However, in vitro data suggest that clindamycin is an inhibitor of CYP3A4 and may increase concentrations of ventoclax, thus increasing the risk of adverse events. However, the clinical relevance of this interaction is unknown. Therefore, coadministration should be approached with caution during the initiation and dose-titration phase to minimize the risk of tumour lysis syndrome. Selection of an alternate concomitant medicinal product with no or minimal potential to inhibit CYP3A4 should be considered. If coadministration is unavoidable, a dose reduction of venetoclax by at least 50% during the initiation, titration phase and steady daily dose should be considered. Close monitoring for signs and symptoms of tumor lysis syndrome is recommended. The venetoclax dose that was used prior to initiation of clindamycin should be resumed 2 to 3 days after discontinuation of clindamycin.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clofazimine is largely excreted unchanged in the faeces. Venetoclax does not interact with this excretion pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clofibrate is hydrolysed to an active metabolite, clofibric acid. Excretion of clofibric acid glucuronide is possibly performed via OAT1. Venetoclax does not interact with this pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clomipramine is metabolised by CYPs 3A4, 1A2 and 2C19 to desmethylclomipramine, an active metabolite which has a higher activity than the parent drug. Clomipramine and desmethylclomipramine are both metabolised by CYP2D6. Venetoclax does not inhibit or induce CYPs.

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 but is unlikely to interfere with venetoclax elimination. In addition, venetoclax does not interfere with clonidine elimination.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clorazepate is rapidly converted to nordiazepam which is then metabolised to oxazepam by CYP3A4. Venetoclax does not inhibit or induce CYPs.

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. Venetoclax does not interact with this metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Clozapine is metabolised mainly by CYP1A2 and CYP3A4 and to a lesser extent by CYP2C19 and CYP2D6. Venetoclax does not inhibit or induce CYPs. However, due to the risk of additive haematological toxicity, haematological parameters should be monitored if coadministered.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. 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. Venetoclax is an inhibitor of P-gp in vitro. However, no clinically relevant interaction is expected, since the systemic exposure of venetoclax is too low to inhibit systemic P-gp. Furthermore, codeine is converted via CYP3A4 to norcodeine, an inactive metabolite. Venetoclax does not inhibit or induce CYPs or UGTs.

Coadministration has not been studied. Colchicine is metabolised by CYP3A4 and is a substrate of P-gp. Venetoclax may inhibit intestinal P-gp at therapeutic doses. In healthy volunteers, coadministration of venetoclax (100 mg single dose) and the P-gp substrate, digoxin (0.5 mg single dose), increased digoxin AUC and Cmax by 9% and 35%, respectively. A similar effect may occur with colchicine. Therefore, colchicine administration should be separated from venetoclax administration as much as possible to minimise a potential interaction. Close monitoring for colchicine toxicity is recommended.

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. Venetoclax does not interact with this elimination pathway.

Coadministration has not been studied. Dabigatran is transported via P-gp and is renally excreted. Venetoclax may inhibit intestinal P-gp at therapeutic doses. In healthy volunteers, coadministration of venetoclax (100 mg single dose) and the P-gp substrate, digoxin (0.5 mg single dose), increased digoxin AUC and Cmax by 9% and 35%, respectively. A similar effect may occur after coadministration with dabigatran. Dabigatran administration should be separated from venetoclax administration as much as possible to minimise a potential interaction. Close monitoring of dabigatran toxicity is recommended.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metabolism of dapsone is mainly by N-acetylation with a component of N-hydroxylation, and is via multiple CYP enzymes. Venetoclax does not inhibit or induce CYPs. 

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

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Desogestrel is a prodrug which is activated to etonogestrel by CYP2C9 (and possibly CYP2C19); the metabolism of etonogestrel is mediated by CYP3A4. Venetoclax does not inhibit or induce CYPs. However, it is currently unknown whether venetoclax may reduce the effectiveness of hormonal contraceptives. Therefore, women using hormonal contraceptives should add a barrier method during treatment with venetoclax and for at least 30 days after the last dose.

Coadministration has not been studied. Dexamethasone is a substrate of CYP3A4. Venetoclax does not inhibit or induce CYPs. Dexamethasone has also been described as an inducer of CYP3A4 and may decrease venetoclax plasma concentrations. However, the clinical relevance of this interaction is unknown as the induction of CYP3A4 by dexamethasone has not yet been established. Monitoring may be required.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Diamorphine is rapidly 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). Morphine is also a substrate of P-gp. Venetoclax may inhibit intestinal P-gp at therapeutic doses. However, no clinically relevant interaction is expected, since the systemic exposure of venetoclax is too low to inhibit systemic P-gp.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Diazepam is metabolised to nordiazepam (by CYP3A4 and CYP2C19) and to temazepam (mainly by CYP3A4). Venetoclax does not inhibit or induce CYPs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Diclofenac is partly glucuronidated by UGT2B7 and partly oxidised by CYP2C9. Venetoclax does not inhibit or induce CYPs or UGTs.

Digoxin is renally eliminated via the renal transporters OATP4C1 and P-gp. Venetoclax may inhibit intestinal P-gp and BCRP at therapeutic doses. In healthy volunteers, coadministration of venetoclax (100 mg single dose) and digoxin (0.5 mg single dose), increased digoxin AUC and Cmax by 9% and 35%, respectively. Digoxin administration should be separated from venetoclax administration as much as possible to minimise a potential interaction. Close monitoring for digoxin toxicity is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dihydrocodeine undergoes predominantly direct glucuronidation, with CYP3A4 mediated metabolism accounting for only 5-10% of the overall metabolism. Venetoclax does not inhibit or induce CYPs or UGTs. 

Coadministration has not been studied. Diltiazem is metabolised by CYP3A4 and CYP2D6. Venetoclax does not inhibit or induce CYPs. However, diltiazem is a moderate inhibitor of CYP3A4 and may increase venetoclax concentrations. In a PBPK simulation, coadministration of venetoclax (400 mg single dose) and diltiazem (60 mg three times daily) increased venetoclax AUC and Cmax by 2.5- and 1.5-fold, respectively. Therefore, coadministration should be avoided at initiation and during the dose-titration phase to minimize the risk of tumour lysis syndrome. Selection of an alternate concomitant medicinal product with no or minimal potential to inhibit CYP3A4 should be considered. If coadministration is unavoidable, reduce the venetoclax dose by at least 50% during the initiation, titration phase and steady daily dose. Close monitoring for signs and symptoms of tumor lysis syndrome is recommended. The venetoclax dose that was used prior to initiation of diltiazem should be resumed 2 to 3 days after discontinuation of diltiazem.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dipyridamole is glucuronidated by many UGTs, specifically those of the UGT1A subfamily. Venetoclax does not inhibit or induce UGTs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Disopyramide is metabolised by CYP3A4 (25%) and 50% of the drug is eliminated unchanged in the urine. Venetoclax 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. 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%). Venetoclax does not interfere with this pathway. 

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

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

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

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

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. Venetoclax does not interact with this elimination pathway. 

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

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Drospirenone is metabolised to a minor extent via CYP3A4. Venetoclax does not inhibit or induce CYPs. However, it is currently unknown whether venetoclax may reduce the effectiveness of hormonal contraceptives. Therefore, women using hormonal contraceptives should add a barrier method during treatment with venetoclax and for at least 30 days after the last dose.

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

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

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dydrogesterone is metabolised to dihydrodydrogesterone (possibly via CYP3A4). Venetoclax does not inhibit or induce CYPs. 

Coadministration has not been studied. Edoxaban is partially metabolised by CYP3A4 (<10%) and is transported via P-gp. Venetoclax may inhibit intestinal P-gp at therapeutic doses. In healthy volunteers, coadministration of venetoclax (100 mg single dose) and the P-gp substrate, digoxin (0.5 mg single dose), increased digoxin AUC and Cmax by 9% and 35%, respectively. A similar effect may occur after coadministration with edoxaban. Edoxaban administration should be separated from venetoclax administration as much as possible to minimise a potential interaction. Close monitoring of edoxaban toxicity is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Eltrombopag is metabolised by cleavage conjugation (via UGT1A1 and UGT1A3) and oxidation (via CYP1A2 and CYP2C8). Venetoclax does not inhibit or induce UGTs or CYPs.

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

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

Coadministration has not been studied. Erythromycin is a substrate of CYP3A4. Venetoclax does not inhibit or induce CYPs. However, erythromycin is a moderate inhibitor of CYP3A4 and may increase concentrations of venetoclax. In a PBPK simulation, coadministration of venetoclax (400 mg once daily) and erythromycin (500 mg four times daily) increased venetoclax AUC and Cmax by 4.9- and 2-fold, respectively. Therefore, coadministration should be avoided during the initiation and dose-titration phase to minimize the risk of tumour lysis syndrome. Selection of an alternate concomitant medicinal product with no or minimal potential to inhibit CYP3A4 should be considered. If coadministration is unavoidable, reduce the venetoclax dose by at least 50% during the initiation, dose-titration phase and steady daily dose. Close monitoring for signs and symptoms of tumor lysis syndrome is recommended. The venetoclax dose that was used prior to initiation of erythromycin should be resumed 2 to 3 days after discontinuation of erythromycin.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Escitalopram is metabolised by CYPs 2C19 (37%), 2D6 (28%) and 3A4 (35%) to form N-desmethylescitalopram. Venetoclax does not inhibit or induce CYPs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Esomeprazole is metabolised by CYP2C19 and CYP3A4, and is also an inhibitor of CYP2C19. Venetoclax does not interact with this pathway. The solubility of venetoclax is extremely low over the whole pH range. Given that venetoclax is to be administered with food, at a state with somewhat increased gastric pH and where solubilising agents in the food and gastric fluids are likely to increase bioavailability, acid-reducing agents are not expected to affect venetoclax bioavailability.

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

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Estradiol is metabolised by CYP3A4, CYP1A2 and is glucuronidated. Venetoclax does not inhibit or induce CYPs or UGTs. However, it is currently unknown whether venetoclax may reduce the effectiveness of hormonal contraceptives. Therefore, women using hormonal contraceptives should add a barrier method during treatment with venetoclax and for at least 30 days after the last dose.

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%). Venetoclax does not interact with this metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Ethinylestradiol undergoes oxidation (CYP3A4>CYP2C9), sulfation and glucuronidation (UGT1A1). Venetoclax does not inhibit or induce CYPs or UGTs. However, it is currently unknown whether venetoclax may reduce the effectiveness of hormonal contraceptives. Therefore, women using hormonal contraceptives should add a barrier method during treatment with venetoclax and for at least 30 days after the last dose.

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

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Etonogestrel is metabolised by CYP3A4. Venetoclax does not inhibit or induce CYPs. However, it is currently unknown whether venetoclax may reduce the effectiveness of hormonal contraceptives. Therefore, women using hormonal contraceptives should add a barrier method during treatment with venetoclax and for at least 30 days after the last dose.

Coadministration has not been studied. Everolimus is mainly metabolised via CYP3A4 and is a substrate of P-gp. Venetoclax may inhibit intestinal P-gp and BCRP at therapeutic doses. In healthy volunteers, coadministration of venetoclax (100 mg single dose) and the P-gp substrate, digoxin (0.5 mg single dose), increased digoxin AUC and Cmax by 9% and 35%, respectively. A similar effect may occur with everolimus. Therefore, everolimus administration should be separated from venetoclax administration as much as possible to minimise a potential interaction. Close monitoring of everolimus toxicity and blood concentrations (if available) is recommended. Due to the risk of additive haematological toxicity, haematological parameters should also be monitored if coadministered.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Exenatide is cleared mainly by glomerular filtration. Exenatide delays gastric emptying and could possibly decrease the absorption rate of concomitantly administered oral drugs. The clinical relevance of delayed absorption is considered to be limited.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ezetimibe is glucuronidated by UGTs 1A1 and 1A3 and to a lesser extent by UGTs 2B15 and 2B7. Venetoclax does not inhibit or induce UGTs. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Famotidine is excreted via OAT1/OAT3. Venetoclax does not inhibit or induce OATs. The solubility of venetoclax is extremely low over the whole pH range. Given that venetoclax is to be administered with food, at a state with somewhat increased gastric pH and where solubilising agents in the food and gastric fluids are likely to increase bioavailability, acid-reducing agents are not expected to affect venetoclax bioavailability.

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

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

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

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

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

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Flecainide is metabolised mainly via CYP2D6, with a proportion (approximately 30%) of the parent drug also renally eliminated unchanged. Venetoclax 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. Flucloxacillin is mainly renally eliminated partly by glomerular filtration and partly by active secretion via OAT1. Venetoclax does not interact with this metabolic pathway.

Coadministration has not been studied. Fluconazole is cleared primarily by renal elimination and is an inhibitor of CYPs 3A4 (moderate), 2C9 and 2C19. Concentrations of venetoclax may increase due to inhibition of CYP3A4. Therefore, coadministration should be avoided at initiation and during the dose-titration phase to minimize the risk of tumour lysis syndrome. Selection of an alternate concomitant medicinal product with no or minimal potential to inhibit CYP3A4 should be considered. If coadministration is unavoidable, reduce the venetoclax dose by at least 50% during the initiation, titration phase and steady daily dose. Close monitoring for signs and symptoms of tumor lysis syndrome is recommended. The venetoclax dose that was used prior to initiation of fluconazole should be resumed 2 to 3 days after discontinuation of fluconazole.

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. Venetoclax does not interfere with the elimination of flucytosine. 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. Venetoclax also induces haematological toxicity which could be enhanced by the use of flucytosine. Due to the risk of additive haematological toxicity, haematological parameters should be monitored if coadministered.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Flunitrazepam is metabolised mainly via CYP3A4 and CYP2C19. Venetoclax does not inhibit or induce CYPs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fluoxetine is metabolised by CYP2D6 and CYP2C9, and to a lesser extent by CYP2C19 and CYP3A4 to form norfluoxetine. Venetoclax does not inhibit or induce CYPs. Furthermore, fluoxetine is a weak inhibitor of CYP3A4 and may slightly increase concentrations of venetoclax. However, in a PBPK simulation, coadministration of venetoclax (400 mg single dose) and fluoxetine (40 mg once daily), did not have any effect on venetoclax exposure. Therefore, no a priori dose adjustment is recommended.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. The metabolism of flurazepam is most likely CYP-mediated. Venetoclax does not inhibit or induce CYPs.

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

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fluvoxamine is metabolised mainly by CYP2D6 and to a lesser extent by CYP1A2. Venetoclax does not inhibit or induce CYPs. Furthermore, fluvoxamine is an inhibitor of CYPs 1A2, 2C19, 3A4, 2C9. However, in a PBPK simulation, coadministration of venetoclax (400 mg single dose) and fluvoxamine (50 mg once daily), did not have any effect on venetoclax exposure. Therefore, no a priori dose adjustment is recommended.

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. Venetoclax does not interact with this metabolic pathway.

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

Coadministration has not been studied but should be approached with caution. Fosaprepitant is rapidly, almost completely, converted to the active metabolite aprepitant. Venetoclax does not interact with this metabolic pathway. Aprepitant is mainly metabolised by CYP3A4 and to a lesser extent by CYP1A2 and CYP2C19. Venetoclax does not inhibit or induce CYPs. However, during treatment aprepitant is a moderate inhibitor of CYP3A4 and may increase concentrations of venetoclax during the three days of coadministration. Therefore, coadministration should be avoided during the initiation and dose-titration phase to minimise the risk of tumour lysis syndrome. Selection of an alternate concomitant medicinal product with no or minimal potential to inhibit CYP3A4 should be considered. If coadministration is unavoidable, reduce the venetoclax dose by at least 50% during the initiation, titration phase and steady daily dose. Close monitoring for signs and symptoms of tumor lysis syndrome is recommended. Furthermore, after treatment aprepitant is a weak inducer of CYP3A4, CYP2C9 and UGT. Concentrations of venetoclax may decrease due to weak induction of CYP3A4, but this is not considered to be clinically not relevant.

Coadministration has not been studied but should be avoided. Fosphenytoin is rapidly converted to the active metabolite phenytoin. Phenytoin is then mainly metabolised by CYP2C9 and to a lesser extent by CYP2C19. Venetoclax does not inhibit or induce CYPs. However, phenytoin is a potent inducer of CYP3A4, UGT and P-gp. Concentrations of venetoclax may significantly decrease due to induction of CYP3A4. A decrease in exposure can lead to decreased efficacy. In healthy volunteers (n=10), coadministration of venetoclax (200 mg single dose) and the strong CYP3A4 inducer, rifampicin (600 mg once daily for 13 days), decreased venetoclax AUC and Cmax by 71% and 42%, respectively. A similar effect may occur with fosphenytoin. Therefore, coadministration should be avoided. Selection of an alternate concomitant medicinal product, with no or minimal potential to induce CYP3A4 should be considered. Increasing the dose of venetoclax when coadministering with strong or moderate CYP3A inducers is unlikely to sufficiently compensate for the loss of exposure.

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

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Gemfibrozil is metabolised by UGT2B7. Venetoclax does not inhibit or induce UGTs. 

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. Venetoclax does not interact with this elimination pathway. 

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Gestodene is metabolised by CYP3A4 and to a lesser extent by CYP2C9 and CYP2C19. Venetoclax does not inhibit or induce CYPs. However, it is currently unknown whether venetoclax may reduce the effectiveness of hormonal contraceptives. Therefore, women using hormonal contraceptives should add a barrier method during treatment with venetoclax and for at least 30 days after the last dose.

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

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

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

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

Coadministration has not been studied. Granisetron is metabolised by CYP3A4. Venetoclax does not inhibit or induce CYPs. However, granisetron is substrate of P-gp. Venetoclax may inhibit intestinal P-gp and BCRP at therapeutic doses. In healthy volunteers, coadministration of venetoclax (100 mg single dose) and the P-gp substrate, digoxin (0.5 mg single dose), increased digoxin AUC and Cmax by 9% and 35%, respectively. A similar effect may occur with granisetron. Monitoring for signs and symptoms of increased exposure to granisetron should be considered. Note: For administration routes other than oral, no clinically relevant interactions are expected, since systemic exposure of venetoclax is too low to inhibit systemic P-gp.

Coadministration has not been studied. Grapefruit juice is a known inhibitor of CYP3A4 and could potentially increase venetoclax concentrations. Therefore coadministration should to 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. Venetoclax does not interfere with the elimination of griseofulvin. 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 venetoclax. If coadministration is necessary, monitor closely for venetoclax efficacy.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Haloperidol has a complex metabolism as it undergoes glucuronidation (UGTs 2B7>1A4 and 1A9), carbonyl reduction, as well as oxidative metabolism (CYP3A4 and CYP2D6). Venetoclax does not interact with this metabolic pathway.

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. Venetoclax 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 venetoclax. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Hydrochlorothiazide is not metabolised and is cleared by the kidneys via OAT1. In vitro data indicate that hydrochlorothiazide is unlikely to inhibit OAT1 in the range of clinically relevant drug concentrations. Significant interactions are not expected with venetoclax.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Hydrocodone is metabolised by CYP2D6 to hydromorphone and by CYP3A4 to norhydrocodone, both of which have analgesic effects. Venetoclax does not inhibit or induce CYPs. 

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

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Hydromorphone is eliminated via glucuronidation, mainly by UGT2B7. Venetoclax not inhibit or induce UGTs. 

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Hydroxyzine is partly metabolised by alcohol dehydrogenase and partly by CYP3A4. Venetoclax does not inhibit or induce CYPs.

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

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

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

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. Venetoclax does not interact with this elimination pathway. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Imipramine is metabolised by CYPs 3A4, 2C19 and 1A2 to desipramine. Imipramine and desipramine are both metabolised by CYP2D6. Venetoclax does not inhibit or induce CYPs. 

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

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

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Interleukin-2 is mainly eliminated by glomerular filtration. Venetoclax does not interfere 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. Venetoclax does not interact with this metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Irbesartan is metabolised by glucuronidation and oxidation (mainly CYP2C9). Venetoclax does not inhibit or induce CYPs or UGTs.

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

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. Venetoclax does not interact with this metabolic pathway. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. In vitro studies suggest that CYP3A4 has a role in nitric oxide formation from isosorbide dinitrate. Venetoclax does not inhibit or induce CYPs.

Coadministration has not been studied but should be avoided. Itraconazole is metabolised by CYP3A4. Venetoclax does not inhibit or induce CYPs. However, itraconazole is an inhibitor of CYP3A4 (strong) and CYP2C9, and may increase concentrations of venetoclax due to CYP3A4 inhibition. In a PBPK simulation, coadministration of venetoclax (400 mg single dose) and itraconazole (200 mg once daily for 43 days) increased venetoclax AUC and Cmax by 5.8- and 2.0-fold, respectively. Coadministration is contraindicated at initiation and during the dose-titration phase to minimise the risk of tumour lysis syndrome. Although coadministration should be avoided after completion of the dose titration phase, if coadministration is necessary for patients who are on a steady daily dose of venetoclax, reduce the venetoclax dose by at least 75%. Close monitoring for signs of toxicities and symptoms of tumor lysis syndrome is recommended. The venetoclax dose may need to be further adjusted. The venetoclax dose that was used prior to initiating itraconazole should be resumed 2 to 3 days after discontinuation of itraconazole.

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

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.

Coadministration should be avoided. Ketoconazole is a substrate and inhibitor of CYP3A4, and may significantly increase concentrations of venetoclax. In patients with non-Hodgkin lymphoma (n=11), coadministration of venetoclax (50 mg single dose) and ketoconazole (400 mg once daily for 7 days) increased venetoclax AUC and Cmax by 6.4- and 2.3-fold, respectively. Furthermore, in a PBPK simulation, coadministration of venetoclax (400 mg single dose) and ketoconazole (400 mg once daily) increased venetoclax AUC and Cmax by 5.8- and 2.5-fold respectively. In the same simulation study, coadministration of venetoclax (400 mg single dose) and ketoconazole (200 mg twice daily) increased venetoclax AUC and Cmax by 7.8- and 2.4-fold, respectively. Therefore, coadministration is contraindicated at initiation and during the dose-titration phase to minimise the risk of tumour lysis syndrome. Although coadministration should be avoided after completion of the dose titration phase, if coadministration is necessary for patients who are on a steady daily dose of venetoclax, reduce the venetoclax dose by at least 75%. Close monitoring for signs of toxicities and symptoms of tumor lysis syndrome is recommended. The venetoclax dose may need to be further adjusted. The venetoclax dose that was used prior to initiating ketoconazole should be resumed 2 to 3 days after discontinuation of ketoconazole.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Labetalol is mainly glucuronidated (via UGT1A1 and UGT2B7). Venetoclax does not inhibit or induce UGTs. 

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

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lansoprazole is mainly metabolised by CYP2C19 and to a lesser extent by CYP3A4. Venetoclax does not inhibit or induce CYPs. Furthermore, the solubility of venetoclax is extremely low over the whole pH range. Given that venetoclax is to be administered with food, at a state with somewhat increased gastric pH and where solubilising agents in the food and gastric fluids are likely to increase bioavailability, acid-reducing agents are not expected to affect venetoclax bioavailability.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Less than 14% of a dose of levocetirizine is metabolised. Levocetirizine is mainly eliminated unchanged in the urine through both glomerular filtration and tubular secretion. Venetoclax does not interact with this elimination pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Levofloxacin is renally eliminated mainly by glomerular filtration and active secretion (possibly OCT2). Venetoclax does not interact with this elimination pathway.

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

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Levonorgestrel is metabolised by CYP3A4 and is glucuronidated to a minor extent. Venetoclax does not inhibit or induce CYPs or UGTs. However, it is currently unknown whether venetoclax may reduce the effectiveness of hormonal contraceptives. Therefore, women using hormonal contraceptives should add a barrier method during treatment with venetoclax and for at least 30 days after the last dose.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Levonorgestrel is metabolised by CYP3A4 and is glucuronidated to a minor extent. Venetoclax does not inhibit or induce CYPs or UGTs. However, it is currently unknown whether venetoclax may reduce the effectiveness of hormonal contraceptives. 

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

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. Venetoclax does not inhibit or induce CYPs. 

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. Venetoclax may inhibit intestinal P-gp at therapeutic doses. In healthy volunteers, coadministration of venetoclax (100 mg single dose) and the P-gp substrate, digoxin (0.5 mg single dose), increased digoxin AUC and Cmax by 9% and 35%, respectively. A similar effect may occur with linagliptin. Since linagliptin has a wide therapeutic index, monitoring for signs and symptoms of increased exposure should be considered. Furthermore, linagliptin is an inhibitor of CYP3A4 and may increase concentrations of venetoclax. As the clinical relevance of this interaction is unknown, close monitoring for venetoclax toxicity and tumour lysis syndrome is recommended. 

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

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

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

Coadministration has not been studied. Loperamide is mainly metabolised by CYP3A4 and CYP2C8. Venetoclax does not inhibit or induce CYPs. However, loperamide is a substrate of P-gp. Venetoclax may inhibit intestinal P-gp at therapeutic doses and may increase concentrations of loperamide. Monitoring of signs and symptoms of increased exposure to loperamide should be considered.

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

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

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Losartan is converted to its active metabolite mainly by CYP2C9 in the range of clinical concentrations. Venetoclax does not inhibit or induce CYPs. 

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

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Magnesium is eliminated in the kidney, mainly by glomerular filtration. Venetoclax 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. Venetoclax does not inhibit or induce CYPs. 

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Medroxyprogesterone is metabolised by CYP3A4. Venetoclax does not inhibit or induce CYPs. However, it is currently unknown whether venetoclax may reduce the effectiveness of hormonal contraceptives. Therefore, women using hormonal contraceptives should add a barrier method during treatment with venetoclax and for at least 30 days after the last dose.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Medroxyprogesterone is metabolised by CYP3A4. Venetoclax does not inhibit or induce CYPs. However, it is currently unknown whether venetoclax may reduce the effectiveness of hormonal contraceptives. Therefore, women using hormonal contraceptives should add a barrier method during treatment with venetoclax and for at least 30 days after the last dose.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Megestrol acetate is mainly eliminated in the urine. Venetoclax does not interfere 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 OAT3>OAT1. Venetoclax does not interfere with this elimination pathway. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Mesalazine is metabolised to N-acetyl-mesalazine by N-acetyltransferase. Venetoclax does not interfere with this 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. Venetoclax does not interact with this metabolic pathway. However, metamizole is an inducer of CYP3A4 and may decrease concentrations of venetoclax. A decrease in exposure can lead to decreased efficacy. Therefore, selection of an alternate concomitant medicinal product, with no or minimal potential to induce CYP3A4 should be considered. If coadministration is necessary, monitor closely for venetoclax efficacy.

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). Venetoclax does not interact with this elimination pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Methadone is demethylated by CYP3A4. Venetoclax does not inhibit or induce CYP3A4.

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 venetoclax, or to be altered by coadministration with venetoclax.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Methylphenidate is not metabolised by CYPs to a clinically relevant extent and does not inhibit or induce CYPs. Venetoclax does not interact with this pathway.

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

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

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. Venetoclax does not interfere with this pathway.

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

Coadministration has not been studied but elevated plasma concentrations have been reported for some CYP3A substrates (e.g. tacrolimus, cyclosporine) 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 venetoclax cannot be excluded and close monitoring is recommended.

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

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

Coadministration has not been studied but should be avoided. Miconazole is extensively metabolised by the liver, potentially CYP-mediated. Venetoclax does not interfere with this metabolic pathway. However, miconazole is an inhibitor of CYP2C9 and CYP3A4. Concentrations of venetoclax may increase due to CYP3A4 inhibition. In patients with non-Hodgkin lymphoma (n=11), coadministration of venetoclax (50 mg single dose) and the strong CYP3A4 inhibitor, ketoconazole (400 mg once daily for 7 days), increased venetoclax AUC and Cmax by 6.4- and 2.3-fold, respectively. A similar effect may occur after coadministration with miconazole. Coadministration is contraindicated at initiation and during the dose-titration phase to minimise the risk of tumour lysis syndrome. Although coadministration should be avoided after completion of the dose titration phase, if coadministration is necessary for patients who are on a steady daily dose of venetoclax, reduce the venetoclax dose by at least 75%. Close monitoring for signs of toxicities and symptoms of tumor lysis syndrome is recommended. The venetoclax dose may need to be further adjusted. The venetoclax dose that was used prior to initiating miconazole should be resumed 2 to 3 days after discontinuation of miconazole. Note: Oromucosal coadministration of miconazole may increase venetoclax concentrations due to inhibition of CYP3A4. However, no a priori dosage adjustment is recommended for venetoclax with dermal administration of miconazole as systemic exposure of miconazole is limited when used topically.

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

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Milnacipran is mainly eliminated unchanged (50%), and as glucuronides (30%) and oxidative metabolites (20%). Venetoclax is unlikely to interfere with this pathway.

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

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

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

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). Venetoclax does not inhibit or induce UGTs. Morphine is also a substrate of P-gp. Venetoclax may inhibit intestinal P-gp at therapeutic doses. In healthy volunteers, coadministration of venetoclax (100 mg single dose) and the P-gp substrate, digoxin (0.5 mg single dose), increased digoxin AUC and Cmax by 9% and 35%, respectively. A similar effect may occur with morphine. Therefore, monitoring for signs and symptoms of increased morphine exposure should be considered if morphine is administered orally. For administration routes other than oral, no clinically relevant interaction is expected, since the systemic exposure of venetoclax is too low to inhibit systemic P-gp.

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

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Mycophenolate is mainly glucuronidated by UGT1A9 and UGT2B7. Venetoclax does not inhibit or induce UGTs. In addition, inhibition of OAT1/OAT3 renal transporters by mycophenolic acid (active metabolite) is unlikely to interfere with venetoclax elimination. However, due to the risk of additive haematological toxicity, haematological parameters should be monitored if coadministered.

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

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

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

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

Coadministration has not been studied but should be avoided. Nefazodone is metabolised mainly by CYP3A4. Venetoclax does not inhibit or induce CYPs. However, nefazodone is a strong inhibitor of CYP3A4 and may increase venetoclax concentrations. In patients with non-Hodgkin lymphoma (n=11), coadministration of venetoclax (50 mg single dose) and the strong CYP3A4 inhibitor, ketoconazole (400 mg once daily for 7 days), increased venetoclax AUC and Cmax by 6.4- and 2.3-fold, respectively. A similar effect may occur after coadministration with nefazodone. Coadministration is contraindicated at initiation and during the dose-titration phase to minimise the risk of tumour lysis syndrome. Although coadministration should be avoided after completion of the dose titration phase, if coadministration is necessary for patients who are on a steady daily dose of venetoclax, reduce the venetoclax dose by at least 75%. Close monitoring for signs of toxicities and symptoms of tumor lysis syndrome is recommended. The venetoclax dose may need to be further adjusted. The venetoclax dose that was used prior to initiating the CYP3A inhibitor should be resumed 2 to 3 days after discontinuation of nefazodone.

Coadministration has not been studied. Nicardipine is metabolised mainly by CYP3A4 and to a lesser extent by CYP2D6 and CYP2C8. Venetoclax does not inhibit or induce CYPs. However, nicardipine is an inhibitor of CYP3A4 and may increase venetoclax concentrations. Therefore, coadministration should be avoided at initiation and during the dose-titration phase to minimize the risk of tumour lysis syndrome. Selection of an alternate concomitant medicinal product with no or minimal potential to inhibit CYP3A4 should be considered. If coadministration is unavoidable, reduce the venetoclax dose by at least 50% during the initiation, titration phase and steady daily dose. Close monitoring for signs and symptoms of tumor lysis syndrome is recommended. The venetoclax dose that was used prior to initiation of nicardipine should be resumed 2 to 3 days after discontinuation of nicardipine.

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. Venetoclax does not interact with this metabolic pathway. 

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

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

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

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nitrofurantoin is partly metabolised in the liver via glucuronidation and N-acetylation, and partly eliminated in the urine as unchanged drug (30-40%). Venetoclax 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. Norelgestromin is metabolised to norgestrel (possibly by CYP3A4). Venetoclax does not inhibit or induce CYPs. However, it is currently unknown whether venetoclax may reduce the effectiveness of hormonal contraceptives. Therefore, women using hormonal contraceptives should add a barrier method during treatment with venetoclax and for at least 30 days after the last dose.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Norethisterone is extensively biotransformed, first by reduction and then by sulfate and glucuronide conjugation. Venetoclax does not interact with this metabolic pathway. However, it is currently unknown whether venetoclax may reduce the effectiveness of hormonal contraceptives. Therefore, women using hormonal contraceptives should add a barrier method during treatment with venetoclax and for at least 30 days after the last dose.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Norgestimate is rapidly deacetylated to the active metabolite which is further metabolised via CYP450. Venetoclax does not interact with this metabolic pathway. However, it is currently unknown whether venetoclax may reduce the effectiveness of hormonal contraceptives. Therefore, women using hormonal contraceptives should add a barrier method during treatment with venetoclax and for at least 30 days after the last dose.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Norgestrel is a racemic mixture with levonorgestrel being biologically active. Levonorgestrel is mainly metabolised by CYP3A4. Venetoclax does not inhibit or induce CYPs. However, it is currently unknown whether venetoclax may reduce the effectiveness of hormonal contraceptives. Therefore, women using hormonal contraceptives should add a barrier method during treatment with venetoclax and for at least 30 days after the last dose.

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

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ofloxacin is renally eliminated unchanged by glomerular filtration and active tubular secretion via both cationic and anionic transport systems. Venetoclax 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. Olanzapine is metabolised mainly by CYP1A2, but also by glucuronidation (UGT1A4). Venetoclax does not inhibit or induce CYPs or UGTs. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Olmesartan medoxomil is de-esterified to the active metabolite olmesartan which is eliminated in the faeces and urine. Venetoclax does not interfere with this pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Omeprazole is mainly metabolised by CYP2C19 and to a lesser extent by CYP3A4. Omeprazole is also an inducer of CYP1A2 and inhibits CYP2C19. Venetoclax does not interact with this pathway. Furthermore, the solubility of venetoclax is extremely low over the whole pH range. Given that venetoclax is to be administered with food, at a state with somewhat increased gastric pH and where solubilising agents in the food and gastric fluids are likely to increase bioavailability, acid-reducing agents are not expected to affect venetoclax bioavailability.

Coadministration has not been studied. Ondansetron is metabolised mainly by CYP1A2 and CYP3A4 and to a lesser extent by CYP2D6. Venetoclax does not inhibit or induce CYPs. However, ondansetron is substrate of P-gp. Venetoclax may inhibit intestinal P-gp at therapeutic doses. In healthy volunteers, coadministration of venetoclax (100 mg single dose) and the P-gp substrate, digoxin (0.5 mg single dose), increased digoxin AUC and Cmax by 9% and 35%, respectively. A similar effect may occur with ondansetron. Monitoring for signs and symptoms of increased exposure to ondansetron should be considered. Note: For administration routes other than oral, no clinically relevant interactions are expected, since systemic exposure of venetoclax is too low to inhibit systemic P-gp.

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

Coadministration has not been studied but should be avoided. Oxcarbazepine is extensively metabolised to the active metabolite monohydroxyderivate (MHD) through cystolic enzymes. Venetoclax does not interact with this pathway. However, both oxcarbazepine and MHD are inducers of CYP3A4 (moderate) and CYP3A5, and are inhibitors of CYP2C19. Concentrations of venetoclax may significantly decrease due to induction of CYP3A4. A decrease in exposure can lead to decreased efficacy. In healthy volunteers (n=10), coadministration of venetoclax (200 mg single dose) and the strong CYP3A4 inducer, rifampicin (600 mg once daily for 13 days), decreased venetoclax AUC and Cmax by 71% and 42%, respectively. A similar effect may occur with oxcarbazepine. Therefore, coadministration should be avoided. Selection of an alternate concomitant medicinal product, with no or minimal potential to induce CYP3A4 should be considered. Increasing the dose of venetoclax when coadministering with strong or moderate CYP3A inducers is unlikely to sufficiently compensate for the loss of exposure.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Oxprenolol is largely metabolised via glucuronidation. Venetoclax does not inhibit or induce UGTs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Oxycodone is metabolised principally to noroxycodone via CYP3A and oxymorphone via CYP2D6. Venetoclax does not inhibit or induce CYPs. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Paliperidone is primarily eliminated renally (possibly via OCT) with minimal metabolism occurring via CYP2D6 and CYP3A4. Venetoclax does not inhibit or induce CYPs.

Coadministration has not been studied. Palonosetron is metabolised mainly by CYP3A4 and to a lesser extent by CYP2D6 and CYP1A2. Venetoclax does not inhibit or induce CYPs. However, palonosetron is substrate of P-gp. Venetoclax may inhibit intestinal P-gp at therapeutic doses. In healthy volunteers, coadministration of venetoclax (100 mg single dose) and the P-gp substrate, digoxin (0.5 mg single dose), increased digoxin AUC and Cmax by 9% and 35%, respectively. A similar effect may occur with palonosetron. Monitoring for signs and symptoms of increased exposure to palonosetron should be considered. Note: For administration routes other than oral, no clinically relevant interactions are expected, since systemic exposure of venetoclax is too low to inhibit systemic P-gp.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pamidronic acid is not metabolised but is cleared from the plasma by uptake into bone and elimination via renal excretion. Venetoclax does not interact with this pathway. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pantoprazole is mainly metabolised by CYP2C19 and to a lesser extent by CYPs 3A4, 2D6 and 2C9. Venetoclax does not inhibit or induce CYPs. The solubility of venetoclax is extremely low over the whole pH range. Given that venetoclax is to be administered with food, at a state with somewhat increased gastric pH and where solubilising agents in the food and gastric fluids are likely to increase bioavailability, acid-reducing agents are not expected to affect venetoclax bioavailability.

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. Venetoclax does not interact with this pathway. 

Coadministration has not been but based on metabolism and clearance a clinically significant interaction is unlikely. Paracetamol is mainly metabolised by glucuronidation (via UGTs 1A9 (major), 1A6, 1A1 and 2B15), sulfation, and to a lesser extent by oxidation (CYPs 2E1 (major), 1A2, 3A4 and 2D6). Venetoclax does not interfere with this metabolic pathway.

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

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Penicillins are mainly eliminated in the urine (20% by glomerular filtration and 80% by tubular secretion via OAT). Venetoclax does not interfere with the elimination of penicillins.

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

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Perindopril is hydrolysed to the active metabolite, perindoprilat, and is metabolised to other inactive metabolites. Elimination occurs predominantly via the urine. Venetoclax 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. Perphenazine is metabolised by CYP2D6. Venetoclax does not inhibit or induce CYPs. 

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

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

Coadministration has not been studied but should be avoided. Phenobarbital is metabolised by CYP2C19 and CYP2C9 (major), and to a lesser extent by CYP2E1. Venetoclax does not inhibit or induce CYPs. However, phenobarbital is a strong inducer of CYPs 3A4, 2C9, 2C8 and UGTs. Concentrations of venetoclax may significantly decrease due to induction of CYP3A4. A decrease in exposure can lead to decreased efficacy. In healthy volunteers (n=10), coadministration of venetoclax (200 mg single dose) and the strong CYP3A4 inducer, rifampicin (600 mg once daily for 13 days), decreased venetoclax AUC and Cmax by 71% and 42%, respectively. A similar effect may occur with phenobarbital. Therefore, coadministration should be avoided. Selection of an alternate concomitant medicinal product, with no or minimal potential to induce CYP3A4 should be considered. Increasing the dose of venetoclax when coadministering with strong or moderate CYP3A inducers is unlikely to sufficiently compensate for the loss of exposure.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Phenprocoumon is metabolised by CYP2C9 and CYP3A4. Venetoclax does not inhibit or induce CYPs. However, in healthy volunteers (n=3), coadministration of venetoclax (400 mg single dose) and warfarin (5 mg single dose), increased AUC and Cmax of R-warfarin and S-warfarin by 18-28%. Therefore it is recommended to monitor the INR closely if venetoclax is coadministered with phenprocoumon.

Coadministration has not been studied but should be avoided. Phenytoin is mainly metabolised by CYP2C9 and to a lesser extent by CYP2C19. Venetoclax does not inhibit or induce CYPs. However, phenytoin is a strong inducer of CYP3A4, UGT and P-gp. Concentrations of venetoclax may significantly decrease due to induction of CYP3A4. A decrease in exposure can lead to decreased efficacy. In healthy volunteers (n=10), coadministration of venetoclax (200 mg single dose) and the strong CYP3A4 inducer, rifampicin (600 mg once daily for 13 days), decreased venetoclax AUC and Cmax by 71% and 42%, respectively. A similar effect may occur with phenytoin. Therefore, coadministration should be avoided. Selection of an alternate concomitant medicinal product, with no or minimal potential to induce CYP3A4 should be considered. Increasing the dose of venetoclax when coadministering with strong or moderate CYP3A inducers is unlikely to sufficiently compensate for the loss of exposure.

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. Venetoclax does not inhibit or induce CYPs.

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

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. Venetoclax is unlikely to interfere with this pathway.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. The metabolism of pipotiazine has not been well described but may involve CYP2D6. Venetoclax does not inhibit or induce CYPs. 

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

Coadministration has not been studied. Pitavastatin is metabolised by UGTs 1A3 and 2B7 with minimal metabolism by CYPs 2C9 and 2C8. Venetoclax does not inhibit or induce CYPs or UGTs. However, pitavastatin is a substrate of OATP1B1. Venetoclax is a weak inhibitor of OATP1B1 in vitro and may increase concentrations of pitavastatin. Close monitoring of pitavastatin-related toxicity is recommended. It is also recommended to start with the lowest dose of pitavastatin and titrate up to the desired clinical effect while monitoring for safety.

Coadministration has not been studied but should be avoided. Posaconazole is primarily metabolised by UGTs and is a substrate of P-gp. Venetoclax may inhibit intestinal P-gp at therapeutic doses. In healthy volunteers, coadministration of venetoclax (100 mg single dose) and the P-gp substrate, digoxin (0.5 mg single dose), increased digoxin AUC and Cmax by 9% and 35%, respectively. A similar effect may occur with orally administered posaconazole. For orally administered posaconazole its administration should be separated from venetoclax administration as much as possible to minimise a potential interaction. Close monitoring of posaconazole toxicity is recommended. For administration routes other than oral, no clinically relevant interaction is expected, since the systemic exposure of venetoclax is too low to inhibit systemic P-gp. Furthermore, posaconazole is a strong inhibitor of CYP3A4 and may increase concentrations of venetoclax. In patients with newly diagnosed AML (n=11), coadministration of venetoclax (400 mg once daily for 15 days) and posaconazole (300 mg once daily for 7 days) increased venetoclax AUC and Cmax by 7.1- and 8.8-fold, respectively. Coadministration is contraindicated at initiation and during the dose-titration phase to minimise the risk of tumour lysis syndrome. Although coadministration should be avoided after completion of the dose titration phase, if coadministration is necessary for patients who are on a steady daily dose of venetoclax, reduce the venetoclax dose by at least 75%. Close monitoring for signs of toxicities and symptoms of tumor lysis syndrome is recommended. The venetoclax dose may need to be further adjusted. The venetoclax dose that was used prior to initiating posaconazole should be resumed 2 to 3 days after discontinuation of posaconazole.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Prasugrel is a prodrug and is converted to its active metabolite mainly by CYP3A4 and CYP2B6. Venetoclax does not inhibit or induce CYPs.

Coadministration has not been studied. Pravastatin is minimally metabolised (via CYP3A4). Venetoclax does not inhibit or induce CYPs. However, pravastatin is a substrate of OATP1B1. Venetoclax is a weak inhibitor of OATP1B1 in vitro and may increase concentrations of pravastatin. Close monitoring of pravastatin-related toxicity is recommended. It is also recommended to start with the lowest dose of pravastatin and titrate up to the desired clinical effect while monitoring for safety.

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

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Prednisone is converted to the active metabolite prednisolone by 11-B-hydroxydehydrogenase. Prednisolone is then metabolised by CYP3A4. Venetoclax does not inhibit or induce CYPs. In a PBPK simulation, coadministration of venetoclax (400 mg single dose) and prednisone (10 mg once daily) did not alter venetoclax AUC or Cmax. Therefore no a priori dose adjustment is recommended.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Prochlorperazine is metabolised by CYP2D6 and CYP2C19. Venetoclax does not inhibit or induce CYPs.

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

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. Venetoclax does not inhibit or induce CYPs.

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

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

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

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

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Quinapril is de-esterified to the active metabolite, quinaprilat, which is eliminated primarily by renal excretion via OAT3. Venetoclax does not interact with this pathway. 

Coadministration has not been studied. Quinidine is metabolised by CYP3A4. Venetoclax does not inhibit or induce CYPs. Quinidine is also an inhibitor of P-gp and CYP3A4, and may increase venetoclax concentrations. PBPK simulations indicated no effect of weak CYP3A inhibitors (fluoxetine and fluvoxamine) on venetoclax Cmax or AUC. However, in healthy volunteers (n=12), coadministration of venetoclax (200 mg single dose) and the P-gp inhibitor, rifampicin (600 mg single dose), increased venetoclax AUC and Cmax by 78% and 106%, respectively. Coadministration should be avoided at initiation and during the titration phase. If coadministration is necessary, the US product label recommends reducing the venetoclax dose by at least 50%. Monitor closely for signs of toxicities. The venetoclax dose that was used prior to initiating quinidine should be resumed 2 to 3 days after discontinuation of quinidine.  

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Rabeprazole is mainly metabolised via non-enzymatic reduction and to a lesser extent by CYP2C19 and CYP3A4. Venetoclax does not interact with this pathway. The solubility of venetoclax is extremely low over the whole pH range. Given that venetoclax is to be administered with food, at a state with somewhat increased gastric pH and where solubilising agents in the food and gastric fluids are likely to increase bioavailability, acid-reducing agents are not expected to affect venetoclax bioavailability.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ramipril is hydrolysed to the active metabolite, ramiprilat, and is metabolised to the diketopiperazine ester, diketopiperazine acid and the glucuronides of ramipril and ramiprilat. Venetoclax is not expected to interact with these metabolic pathways. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ranitidine is excreted via OAT1/OAT3. Venetoclax does not inhibit or induce OATs. Furthermore, the solubility of venetoclax is extremely low over the whole pH range. Given that venetoclax is to be administered with food, at a state with somewhat increased gastric pH and where solubilising agents in the food and gastric fluids are likely to increase bioavailability, acid-reducing agents are not expected to affect venetoclax bioavailability.

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. Venetoclax may inhibit intestinal P-gp at therapeutic doses. In healthy volunteers, coadministration of venetoclax (100 mg single dose) and the P-gp substrate, digoxin (0.5 mg single dose), increased digoxin AUC and Cmax by 9% and 35%, respectively. A similar effect may occur with ranolazine. Monitoring for signs and symptoms of increased exposure to ranolazine should be considered. Furthermore, ranolazine is a weak inhibitor of P-gp, CYP3A4 and CYP2D6. Concentrations of venetoclax may increase due to CYP3A4 and P-gp inhibition. PBPK simulations indicated no effect of weak CYP3A inhibitors (fluoxetine and fluvoxamine) on venetoclax Cmax or AUC. However, in healthy volunteers (n=12), coadministration of venetoclax (200 mg single dose) and the P-gp inhibitor, rifampicin (600 mg single dose), increased venetoclax AUC and Cmax by 78% and 106%, respectively. A similar effect may occur with ranolazine. Coadministration of venetoclax and ranolazine at initiation and during the titration phase should be avoided. If coadministration is necessary, the US product label recommends reducing the venetoclax dose by at least 50%. Monitor closely for signs of toxicities. The venetoclax dose that was used prior to initiating of ranolazine should be resumed 2 to 3 days after discontinuation of ranolazine.

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

Coadministration has not been studied. Repaglinide is metabolised by CYP2C8 and CYP3A4, with clinical data indicating it is a substrate of OATP1B1. Venetoclax is a weak inhibitor of OATP1B1 in vitro. As the clinical relevance of this interaction is unknown, monitoring for repaglinide toxicity may be required.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Vitamin A esters are hydrolysed by pancreatic enzymes to retinol, which is then absorbed and re-esterified. Some retinol is stored in the liver but retinol not stored in the liver undergoes glucuronide conjugation and subsequent oxidation to retinal and retinoic acid. Venetoclax 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. Rifabutin is also a potent CYP3A4 and P-gp inducer and may significantly decrease concentrations of venetoclax. Decrease in exposure can lead to decreased efficacy. In healthy volunteers (n=10), coadministration of venetoclax (200 mg single dose) and the strong CYP3A4 inducer, rifampicin (600 mg once daily for 13 days), decreased venetoclax AUC and Cmax by 71% and 42%, respectively. Therefore, coadministration should be avoided. Selection of an alternate concomitant medicinal product, with no or minimal potential to induce CYP3A4 should be considered. Increasing the dose of venetoclax when coadministering with strong or moderate CYP3A inducers is unlikely to sufficiently compensate for the loss of exposure.

Coadministration should be avoided. Rifampicin is metabolised via deacetylation. Venetoclax does not interfere with this metabolic pathway. However, rifampicin is a potent CYP3A4 and P-gp inducer and may significantly decrease concentrations of venetoclax. In healthy volunteers (n=10), coadministration of venetoclax (200 mg single dose) and rifampicin (600 mg once daily for 13 days), decreased venetoclax AUC and Cmax by 71% and 42%, respectively. Furthermore, in a PBPK simulation, coadministration of venetoclax (400 mg single dose) and rifampicin (600 mg once daily) decreased venetoclax AUC and Cmax by 80% and 70%, respectively. Therefore, coadministration should be avoided. Selection of an alternate concomitant medicinal product, with no or minimal potential to induce CYP3A4 should be considered. Increasing the dose of venetoclax when coadministering with strong or moderate CYP3A inducers is unlikely to sufficiently compensate for the loss of exposure.

Coadministration has not been studied but should be avoided. Rifapentine is metabolised via deacetylation. Venetoclax does not interfere with this metabolic pathway. However, rifapentine is also a potent CYP3A4, CYP2C8 and P-gp inducer. Concentrations of venetoclax may significantly decrease due to induction of CYP3A4. In healthy volunteers (n=10), coadministration of venetoclax (200 mg single dose) and the strong CYP3A4 inducer, rifampicin (600 mg once daily for 13 days), decreased venetoclax AUC and Cmax by 71% and 42%, respectively. Therefore, coadministration should be avoided. Selection of an alternate concomitant medicinal product, with no or minimal potential to induce CYP3A4 should be considered. Increasing the dose of venetoclax when coadministering with strong or moderate CYP3A inducers is unlikely to sufficiently compensate for the loss of exposure.

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

Coadministration has not been studied. Risperidone is metabolised by CYP2D6 and to a lesser extent by CYP3A4. Venetoclax does not inhibit or induce CYPs. However, risperidone is a substrate of P-gp. Venetoclax may inhibit intestinal P-gp at therapeutic doses. In healthy volunteers, coadministration of venetoclax (100 mg single dose) and the P-gp substrate, digoxin (0.5 mg single dose), increased digoxin AUC and Cmax by 9% and 35%, respectively. A similar effect may occur with risperidone. Monitoring for signs and symptoms of increased exposure to risperidone should be considered. Note: No clinically relevant interactions are expected with intramuscular administration of risperidone as systemic exposure of venetoclax is too low to inhibit systemic P-gp.

Coadministration has not been studied. Rivaroxaban is partly metabolised in the liver (by CYP3A4, CYP2J2 and hydrolytic enzymes) and partly eliminated unchanged in urine. Rivaroxaban is also a substrate of P-gp and BCRP. Venetoclax may inhibit intestinal P-gp and BCRP at therapeutic doses. In healthy volunteers, coadministration of venetoclax (100 mg single dose) and the P-gp substrate, digoxin (0.5 mg single dose), increased digoxin AUC and Cmax by 9% and 35%, respectively. A similar effect may occur with rivaroxaban. Therefore, rivaroxaban administration should be separated from venetoclax administration as much as possible to minimise a potential interaction. Close monitoring of rivaroxaban toxicity is recommended. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Rosiglitazone is metabolised mainly by CYP2C8 and to a lesser extent by CYP2C9. Venetoclax does not inhibit or induce CYPs.

Coadministration has not been studied. Rosuvastatin is largely excreted unchanged via the faeces via OATP1B1. Rosuvastatin is also a substrate of BCRP. Venetoclax is a weak inhibitor of OATP1B1 in vitro and may increase concentrations of rosuvastatin. Furthermore, venetoclax may inhibit intestinal BCRP at therapeutic doses. Close monitoring of rosuvastatin-related toxicity is recommended. It is also recommended to start with the lowest dose of rosuvastatin and titrate up to the desired clinical effect while monitoring for safety.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Salbutamol is metabolised to the inactive salbutamol-4’-O-sulphate. Venetoclax 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. Venetoclax does not inhibit or induce CYPs.

Coadministration has not been studied. Saxagliptin is mainly metabolised by CYP3A4 and is a substrate of P-gp. Venetoclax may inhibit intestinal P-gp at therapeutic doses. In healthy volunteers, coadministration of venetoclax (100 mg single dose) and the P-gp substrate, digoxin (0.5 mg single dose), increased digoxin AUC and Cmax by 9% and 35%, respectively. A similar effect may occur with saxagliptin. Monitoring for signs and symptoms of increased exposure to saxagliptin should be considered.

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

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

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

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

Coadministration has not been studied. Simvastatin is metabolised by CYP3A4 to its active metabolite. Simvastatin is also a substrate of BCRP and the active metabolite is a substrate of OATP1B1. Venetoclax is a weak inhibitor of OATP1B1 in vitro and may increase concentrations of simvastatin. Venetoclax may also inhibit intestinal BCRP at therapeutic doses. Close monitoring of simvastatin-related toxicity is recommended. It is also recommended to start with the lowest dose of simvastatin and titrate up to the desired clinical effect while monitoring for safety.

Coadministration has not been studied. Sirolimus is metabolised by CYP3A4 and is substrate of P-gp. Venetoclax may inhibit intestinal P-gp and BCRP at therapeutic doses. In healthy volunteers, coadministration of venetoclax (100 mg single dose) and the P-gp substrate, digoxin (0.5 mg single dose), increased digoxin AUC and Cmax by 9% and 35%, respectively. A similar effect may occur with sirolimus. Therefore, sirolimus administration should be separated from venetoclax administration as much as possible to minimise a potential interaction. Close monitoring for sirolimus toxicity is recommended. Due to the risk of additive haematological toxicity, haematological parameters should also be monitored if coadministered.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Sitagliptin is primarily eliminated in urine as unchanged drug (active secretion by OAT3, OATP4C1 and P-gp) and metabolism by CYP3A4 represents a minor elimination pathway. Although venetoclax may inhibit P-gp, no clinically relevant interaction is expected as the systemic exposure of venetoclax is too low to inhibit systemic P-gp.

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 venetoclax, or to be affected if coadministered with venetoclax. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Sotalol is excreted unchanged via renal elimination. Venetoclax 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. Spectinomycin is predominantly eliminated unchanged in the kidneys via glomerular filtration. Venetoclax 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. Venetoclax does not affect this metabolic pathway. 

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

Coadministration of venetoclax with preparations containing St John’s wort are contraindicated during treatment with venetoclax. St John’s wort is a CYP3A4 and P-gp inducer and may decrease venetoclax exposure. A decrease in exposure can lead to a decreased efficacy. In healthy volunteers (n=10), coadministration of venetoclax (200 mg single dose) and the strong CYP3A4 inducer, rifampicin (600 mg once daily for 13 days), decreased venetoclax AUC and Cmax by 71% and 42%, respectively. A similar effect may occur with St John’s Wort. Increasing the dose of venetoclax when coadministering with strong or moderate CYP3A inducers is unlikely to sufficiently compensate for the loss of exposure.

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

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. In vitro studies suggest a role of CYP2C9 in sulfadiazine metabolism. Venetoclax does not inhibit or induce CYPs.

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

Coadministration has not been studied. Tacrolimus is mainly metabolised by CYP3A4. Venetoclax does not inhibit or induce CYPs. Tacrolimus is also an inhibitor of CYP3A4 and OATP1B1 in vitro but produced modest inhibition of CYP3A4 and OATP1B1 in the range of clinical concentrations. Tacrolimus could potentially increase venetoclax concentrations although only to a modest extent. No a priori dosage adjustment is recommended. Furthermore, tacrolimus is a P-gp substrate. Venetoclax may inhibit intestinal P-gp at therapeutic doses. In healthy volunteers, coadministration of venetoclax (100 mg single dose) and the P-gp substrate, digoxin (0.5 mg single dose), increased digoxin AUC and Cmax by 9% and 35%, respectively. A similar effect may occur with tacrolimus. Therefore, tacrolimus administration should be separated from venetoclax administration as much as possible to minimise a potential interaction. Close monitoring for tacrolimus toxicity and blood concentrations is recommended. Due to the risk of additive haematological toxicity, haematological parameters should also be monitored if coadministered.

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

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tazobactam is excreted as unchanged drug (approximately 80%) and inactive metabolite (approximately 20%) in the urine. Venetoclax does not interact with this elimination pathway.

Coadministration has not been studied but should be avoided. Telithromycin is metabolised by CYP3A4 (50%) with the remaining 50% metabolised via non-CYP mediated pathways. Venetoclax does not interfere with this pathway. However, telithromycin is a strong inhibitor of CYP3A4 and may increase concentrations of venetoclax. In patients with non-Hodgkin lymphoma (n=11), coadministration of venetoclax (50 mg single dose) and the strong CYP3A4 inhibitor, ketoconazole (400 mg once daily for 7 days), increased venetoclax AUC and Cmax by 6.4- and 2.3-fold, respectively. A similar effect may occur after coadministration with telithromycin. Coadministration is contraindicated at initiation and during the dose-titration phase to minimise the risk of tumour lysis syndrome. Although coadministration should be avoided after completion of the dose titration phase, if coadministration is necessary for patients who are on a steady daily dose of venetoclax, reduce the venetoclax dose by at least 75%. Close monitoring for signs of toxicities and symptoms of tumor lysis syndrome is recommended. The venetoclax dose may need to be further adjusted. The venetoclax dose that was used prior to initiating the CYP3A inhibitor should be resumed 2 to 3 days after discontinuation of telithromycin.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Telmisartan is mainly glucuronidated by UGT1A3. Venetoclax does not inhibit or induce UGTs. 

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

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

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tetracycline is eliminated unchanged primarily by glomerular filtration. Venetoclax does not interact with the renal elimination of tetracyclines.

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

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

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tiapride is excreted largely unchanged in urine. Venetoclax 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. Ticagrelor undergoes extensive CYP3A4 metabolism and is a weak inhibitor of CYP3A4. Venetoclax does not inhibit or induce CYPs. However, concentrations of venetoclax may slightly increase due to weak inhibition of CYP3A4. PBPK simulations indicated no effect of weak CYP3A inhibitors (fluoxetine and fluvoxamine) on venetoclax Cmax or AUC. Therefore, no clinically significant interaction is expected and no a priori dose adjustment is recommended.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tinzaparin is renally excreted as unchanged or almost unchanged drug. Venetoclax does not interact with this elimination pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tolbutamide is mainly metabolised by CYP2C9 and to a lesser extent by CYPs 2C8 and 2C19. Venetoclax does not inhibit or induce CYPs.