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. Acalabrutinib is unlikely to interfere with this metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Acenocoumarol is mainly metabolised by CYP2C9 and to a lesser extent by CYP1A2 and CYP2C19. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro, but no clinically significant effect on acenocoumarol is expected in vivo. However, coadministration is not recommended due to the increased risk of haemorrhage. If coadministration is unavoidable, monitor closely for signs of bleeding.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Aspirin is rapidly deacetylated to form salicylic acid and then further metabolised by glucuronidation (by several UGTs, major UGT1A6). Acalabrutinib does not inhibit or induce UGTs. However, coadministration is not recommended due to the increased risk of haemorrhage. If coadministration is unavoidable, monitor closely for signs of bleeding.

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%). Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on agomelatine is expected in vivo.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Alendronate is not metabolised but 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. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically significant effect on alfentanil is expected in vivo.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Alfuzosin is metabolised by CYP3A. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on alfuzosin is expected in vivo.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Aliskiren is minimally metabolised and is mainly excreted unchanged in faeces. P-gp is a major determinant of aliskiren bioavailability. Acalabrutinib is a weak inhibitor of P-gp in vitro. However, no clinically relevant effect is expected on aliskiren in vivo.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Allopurinol is converted to oxipurinol by xanthine oxidase and aldehyde oxidase. Acalabrutinib 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. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on alosetron is expected in vivo.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Alprazolam is mainly metabolised by CYP3A4. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on alprazolam is expected in vivo.

Coadministration has not been studied but is not recommended. Aluminium hydroxide is not metabolised. Acalabrutinib is unlikely to interfere with this pathway. However, the solubility of acalabrutinib decreases with increasing pH of the stomach. In healthy volunteers, coadministration of acalabrutinib and the antacid, calcium carbonate, decreased acalabrutinib AUC and Cmax by 53% and 75%, respectively. In the same study, coadministration of acalabrutinib and the proton pump inhibitor, omeprazole, decreased acalabrutinib AUC and Cmax by 57% and 79%, respectively. If coadministration is clinically necessary, separate dosing by at least 2 hours to minimize a potential interaction. Monitoring of acalabrutinib efficacy is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. 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. Acalabrutinib does not inhibit or induce UGTs, but is an in vitro inhibitor and inducer of several CYP enzymes and P-gp. However, no clinically relevant effect on ambrisentan is expected in vivo.

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

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

Coadministration has not been studied but care should be taken. Amiodarone is metabolised by CYP3A4 and CYP2C8. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro, but no clinically relevant effect on amiodarone is expected in vivo. However, 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 acalabrutinib may increase due to inhibition of CYP3A4 and P-gp. As the clinical relevance of these interactions is unknown, monitoring for acalabrutinib toxicity should be considered. No a priori dose adjustment is necessary. 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). Acalabrutinib is unlikely to significantly impair 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. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on amitryptyline is expected in vivo.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amlodipine is metabolised by CYP3A4. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on amlodipine is expected in vivo.

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. Acalabrutinib 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. Acalabrutinib does not interfere with this elimination pathway. However, the European SPC for amphotericin B states that concomitant use of amphotericin B and antineoplastic agents can increase the risk of renal toxicity, bronchospasm and hypotension. 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. Acalabrutinib 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. Acalabrutinib is unlikely to interfere with this metabolic pathway.

Coadministration has not been studied but is not recommended. Antacids are not metabolised by CYPs. Acalabrutinib is unlikely to interfere with this metabolic pathway. However, the solubility of acalabrutinib decreases with increasing pH of the stomach. In healthy volunteers, coadministration of acalabrutinib and the antacid, calcium carbonate, decreased acalabrutinib AUC and Cmax by 53% and 75%, respectively. In the same study, coadministration of acalabrutinib and the proton pump inhibitor, omeprazole, decreased acalabrutinib AUC and Cmax by 57% and 79%, respectively. If coadministration is clinically necessary, separate dosing by at least 2 hours to minimize a potential interaction. Monitoring of acalabrutinib efficacy is recommended.

Coadministration has not been studied but should be approached with caution. Apixaban is metabolised by CYP3A4 and to a lesser extent by CYPs 1A2, 2C8, 2C9 and 2C19. Apixaban is also a substrate of BCRP and P-gp. Acalabrutinib is an in vitro inhibitor and inducer of several CYP enzymes and is a weak inhibitor of P-gp, but no clinically relevant effect on apixaban is expected in vivo. However, acalabrutinib is also an inhibitor of BCRP in the gastrointestinal tract and may increase concentrations of apixaban. As the clinical relevance of this interaction is unknown, monitoring for signs or symptoms of apixaban toxicity is recommended. Furthermore, coadministration may increase the risk of haemorrhage. If coadministration is unavoidable, monitor closely for signs of bleeding.

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. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro, but no clinically relevant effect on aprepitant is expected in vivo. However, during treatment aprepitant is a moderate inhibitor of CYP3A4 and may increase concentrations of acalabrutinib. Increased acalabrutinib concentrations may result in increased toxicity. Therefore, coadministration should be approached with caution. If coadministration is clinically necessary, reduce the acalabrutinib dose by 50% during the few days of coadministration. Furthermore, after treatment aprepitant is a weak inducer of CYP3A4, CYP2C9 and UGT. Concentrations of acalabrutinib may decrease due to induction of CYP3A4. However, this is not considered to be clinically relevant.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Aripiprazole is metabolised by CYP3A4 and CYP2D6. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on aripiprazole is expected in vivo.

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 (minor) and 2D6 (minor)). Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on asenapine is expected in vivo.

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. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on astemizole is expected in vivo.

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. Acalabrutinib does not interfere with this elimination pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Atorvastatin is metabolised by CYP3A4 and is a substrate of P-gp and OATP1B1. Acalabrutinib is an inhibitor and inducer of several CYP enzymes and P-gp in vitro. However, no clinically relevant effect on atorvastatin is expected in vivo.

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

Coadministration has not been studied but care should be taken. Azithromycin is mainly eliminated via biliary excretion with animal data suggesting this may occur via P-gp and MRP2. Acalabrutinib is a weak inhibitor of P-gp in vitro, but no clinically relevant effect on azithromycin is expected in vivo. Azithromycin is also an inhibitor of P-gp and may increase acalabrutinib concentrations. As the clinical relevance of P-gp inhibition by azithromycin is unknown, monitoring for acalabrutinib toxicity may be required.

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. Acalabrutinib does not interact with this metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bedaquiline is metabolised by CYP3A4. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically significant effect on bedaquiline is expected in vivo.

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. OAT1/3 are the major transporters of loop and thiazide diuretics. Acalabrutinib does not interfere with bendroflumethiazide elimination. There is no evidence that bendroflumethiazide inhibits or induces CYP450 enzymes and therefore is unlikely to impact acalabrutinib concentrations.

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. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically significant effect on bepridil is expected in vivo.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Betamethasone is metabolised by CYP3A4. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on betamethasone is expected in vivo.

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. Acalabrutinib does not interact with this pathway.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bisoprolol is partly metabolised by CYP3A4 and CYP2D6, and partly eliminated unchanged in the urine. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on bisoprolol is expected in vivo.

Coadministration has not been studied but should be approached with caution. Bosentan is a substrate of CYP3A4 and CYP2C9. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro, but no clinically relevant effect on bosentan is expected in vivo. However, bosentan is a weak inducer of CYP3A4 and CYP2C9. Concentrations of acalabrutinib may decrease due to induction of CYP3A4. Coadministration of the tyrosine kinase inhibitor, imatinib, and bosentan decreased imatinib concentrations by 33%. A similar effect may occur with acalabrutinib. If coadministration is necessary, close monitoring of acalabrutinib efficacy is required. Monitor acalabrutinib concentrations, if available.

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 play a role. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on bromazepam is expected in vivo.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Budesonide is metabolised by CYP3A4. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on budesonide is expected in vivo.

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). Acalabrutinib is an inhibitor and inducer of several CYP-enzymes in vitro. However, no clinically significant effect on buprenorphine is expected in vivo.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bupropion is primarily metabolised by CYP2B6. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on bupropion is expected in vivo.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Buspirone is metabolised by CYP3A4. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on buspirone is expected in vivo.

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. Acalabrutinib 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. The role of OAT1/3 in the renal secretion of angiotensin II receptor blockers appears limited, as these compounds are mostly excreted through the biliary route. Acalabrutinib does not 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. Acalabrutinib 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. Acalabrutinib does not inhibit or induce OATs.

Coadministration has not been studied but should be avoided. Carbamazepine is primarily metabolised by CYP3A4 and to a lesser extent by CYP2C8. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on carbamazepine is expected in vivo. Furthermore, carbamazepine is an inducer of CYPs 2C8 (strong), 2C9 (strong), 3A4 (strong), 1A2 (weak), 2B6 and UGT1A1. Concentrations of acalabrutinib may decrease due to strong induction of CYP3A4. In healthy volunteers, coadministration of acalabrutinib and the strong CYP3A4 inducer, rifampicin, decreased acalabrutinib AUC and Cmax by 77% and 68%, respectively. A similar effect may occur with carbamazepine. A decrease in acalabrutinib exposure may lead to decreased efficacy. Therefore, coadministration should be avoided. If coadministration is unavoidable, the FDA product label recommends increasing the acalabrutinib dose to 200 mg twice daily. Closely monitor acalabrutinib efficacy. Monitor acalabrutinib concentrations, if available.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Carvedilol undergoes glucuronidation via UGTs 1A1, 2B4 and 2B7, and additional metabolism via CYP2D6 and to a lesser extent CYPs 2C9 and 1A2. Acalabrutinib does not inhibit or induce UGTs, but is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on carvedilol is expected in vivo.

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. Acalabrutinib 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. Acalabrutinib 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. Acalabrutinib 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. Acalabrutinib 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. Acalabrutinib 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. Acalabrutinib 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. Acalabrutinib 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. Acalabrutinib is an inhibitor and inducer of several CYP-enzymes in vitro. However, no clinically significant effect on celecoxib is expected in vivo.

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 (possibly via OCT2). In vitro data indicate that cetirizine inhibits OCT2. Acalabrutinib is unlikely to interact with this elimination pathway.

Coadministration has not been studied. Chloramphenicol is predominantly glucuronidated. Acalabrutinib does not inhibit or induce UGTs. However, in vitro studies have shown that chloramphenicol can inhibit metabolism mediated by CYPs 3A4 (strong), 2C19 (strong) and 2D6 (weak). Concentrations of acalabrutinib may increase due to CYP3A4 inhibition, increasing the risk of adverse events. As the clinical relevance of this interaction is unknown, monitoring for acalabrutinib toxicity should be considered. No a priori dose adjustment for acalabrutinib is necessary. Ocular use: Although chloramphenicol is systemically absorbed when used topically in the eye, the absorbed concentrations 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. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on chlordiazepoxide is expected in vivo.

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. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on chlorphenamine is expected in vivo.

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. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on chlorpromazine is expected in vivo.

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. OAT1/3 are the major transporters of loop and thiazide diuretics. Secretion of these diuretics into the urinary tract by transporters in the proximal tubular cells is necessary for the diuretic effect in later tubule segments. Acalabrutinib does not interfere with this elimination pathway.

Coadministration has not been studied. Ciclosporin is a substrate of CYP3A4 and P-gp. Acalabrutinib is an inhibitor and inducer of several CYP enzymes and P-gp in vitro, but no clinically relevant effect on ciclosporin is expected in vivo. However, ciclosporin is an inhibitor of CYP3A4 and OATP1B1. Concentrations of acalabrutinib may increase due to inhibition of CYP3A4. As the clinical relevance of this interaction is unknown, monitoring for acalabrutinib toxicity should be considered. No a priori dose adjustment is necessary.

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 (possibly via OATs). Acalabrutinib does not interfere with this elimination pathway.

Coadministration has not been studied but should be avoided. Cimetidine is metabolised by CYP450 enzymes. Acalabrutinib is an inhibitor and inducer of several CYP-enzymes in vitro. However, no clinically relevant effect on cimetidine is expected in vivo. Cimetidine is a weak inhibitor of several CYP enzymes (CYPs 3A4, 1A2, 2D6 and 2C19). In vitro data indicate that cimetidine also inhibits OAT1 and OCT2 but at concentrations much higher than the observed clinical concentrations. Concentrations of acalabrutinib may increase due to weak inhibition of CYP3A4. As the clinical relevance of this interaction is unknown, monitoring for acalabrutinib toxicity should be considered. No a priori dose adjustment is necessary. Furthermore, the solubility of acalabrutinib decreases with increasing pH of the stomach. In healthy volunteers, coadministration of acalabrutinib and the antacid, calcium carbonate, decreased acalabrutinib AUC and Cmax by 53% and 75%, respectively. In the same study, coadministration of acalabrutinib and the proton pump inhibitor, omeprazole, decreased acalabrutinib AUC and Cmax by 57% and 79%, respectively. Due to the twice daily regimen of acalabrutinib and the lasting effect of H2 receptor antagonists, separation of doses may not eliminate an interaction with acalabrutinib. If coadministration with a gastric acid reducing agent is clinically necessary, consider using an antacid (calcium carbonate). If administration of an antacid is clinically necessary, separate dosing by at least 2 hours to minimize a potential interaction. Monitoring of acalabrutinib efficacy is recommended.

Coadministration has not been studied but should be approached with caution. Ciprofloxacin is primarily eliminated unchanged in the kidneys by glomerular filtration and tubular secretion via OAT3. It is also metabolised and partially cleared through the bile and intestine. Acalabrutinib does not interfere with this elimination pathway. However, ciprofloxacin is a weak to moderate inhibitor of CYP3A4 and a strong inhibitor of CYP1A2. Concentrations of acalabrutinib may increase due to moderate inhibition of CYP3A4. Increased acalabrutinib concentrations may result in increased toxicity. Therefore, coadministration should be approached with caution. If coadministration is clinically necessary, the FDA product label recommends a dose reduction of acalabrutinib to 100 mg once daily. Monitor closely for acalabrutinib toxicity. Monitor acalabrutinib concentrations, if available.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cisapride is metabolised by CYP3A4. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on cisapride is expected in vivo.

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%). Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on citalopram is expected in vivo.

Coadministration has not been studied but should be avoided. Clarithromycin is a substrate of CYP3A4. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro, but no clinically relevant effect on clarithromycin is expected in vivo. However, clarithromycin is an inhibitor of CYP3A4 (strong) and P-gp, and may increase concentrations of acalabrutinib. Coadministration of acalabrutinib and itraconazole increased acalabrutinib Cmax by 3.9-fold and AUC by 5.1-fold. A similar effect may occur with clarithromycin. Increased acalabrutinib concentrations may result in increased toxicity. Therefore, coadministration should be avoided. However, if the inhibitor will be used short-term (such as anti-infectives) and if use of clarithromycin cannot be avoided, withhold acalabrutinib treatment temporarily (for 7 days or less). Monitor closely for acalabrutinib toxicity.

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. Acalabrutinib does not interact with this elimination pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clemastine is predominantly metabolised in the liver via CYP2D6. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on clemastine is expected in vivo.

Coadministration has not been studied. Clindamycin is metabolised by CYP3A4. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro, but no clinically significant effect on clindamycin is expected in vivo. However, in vitro data suggest that clindamycin is a CYP3A4 inhibitor and may increase concentrations of acalabrutinib. As the clinical relevance of this interaction is unknown, monitoring for acalabrutinib toxicity should be considered. No a priori dose adjustment is necessary.

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. Clofazimine is largely excreted unchanged in the faeces. Acalabrutinib does not interact with this elimination pathway. However, in vitro data suggest that clofazimine is a CYP3A4 inhibitor and may increase concentrations of acalabrutinib. As the clinical relevance of this interaction is unknown, monitoring for acalabrutinib toxicity should be considered. No a priori dose adjustment is necessary.

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. Acalabrutinib does not interact with this metabolic 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. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on clomipramine is expected in vivo.

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 also a weak inhibitor of OCT2. Acalabrutinib does not interact with this pathway.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Clopidogrel is a prodrug and is converted to its active metabolite mainly through CYP2C19 with CYPs 3A4, 2B6 and 1A2 playing a minor role. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro, but no clinically significant effect on clopidogrel is expected in vivo. Furthermore, clopidogrel is an inhibitor of CYP2C8 (strong), CYP2B6 (weak) and of CYP2C9 (in vitro) at high concentrations. Acalabrutinib is not metabolised by these CYPs. However, coadministration is not recommended due to the increased risk of haemorrhage. If coadministration is unavoidable, monitor closely for signs of bleeding.

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. Oxazepam is mainly glucuronidated. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on clorazepate is expected in vivo.

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. Acalabrutinib 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. Clozapine is metabolised mainly by CYP1A2 and CYP3A4, and to a lesser extent by CYP2C19 and CYP2D6. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro, but no clinically relevant effect on clozapine is expected in vivo. 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). Codeine is converted via CYP3A4 to norcodeine, an inactive metabolite. The metabolite morphine is also a substrate of P-gp. Acalabrutinib is an in vitro inhibitor and inducer of several CYP-enzymes and a weak inhibitor of P-gp. However, no clinically significant effect on codeine or morphine is expected in vivo.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Colchicine is metabolised by CYP3A4. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on colchicine is expected in vivo.

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

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Dabigatran is transported via P-gp and is excreted renally. Acalabrutinib is a weak inhibitor of P-gp in vitro, but no clinically significant effect on dabigatran is expected. However, coadministration is not recommended due to the increased risk of haemorrhage. If coadministration is unavoidable, monitor closely for signs of bleeding.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Dalteparin is excreted largely unchanged via the kidneys. Acalabrutinib is unlikely to interfere with the renal excretion of dalteparin. However, coadministration is not recommended due to the increased risk of haemorrhage. If coadministration is unavoidable, monitor closely for signs of bleeding.

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. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically significant effect on dapsone is expected in vivo.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Desipramine is metabolised by CYP2D6. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on desipramine is expected in vivo.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Desogestrel is a prodrug which is activated to etonogestrel by CYP2C9 (and possibly CYP2C19); the metabolism of etonogestrel is mediated by CYP3A4. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on desogestrel is expected in vivo.

Coadministration has not been studied. Dexamethasone is a known substrate of CYP3A4. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro, but no clinically relevant effect on dexamethasone is expected in vivo. However, dexamethasone has also been described as a weak inducer of CYP3A4, and may decrease concentrations of acalabrutinib. The clinical relevance of this interaction is unknown as the CYP3A4 induction effect by dexamethasone has yet to be established. Monitoring of acalabrutinib efficacy 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. Acalabrutinib is an inhibitor and inducer of several CYP-enzymes in vitro. However, no clinically significant effect on dextropropoxyphene is expected in vivo.

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. Acalabrutinib is a weak inhibitor of P-gp in vitro, but no clinically significant effect on morphine is expected in vivo.

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). Temazepam is mainly glucuronidated. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on diazepam is expected in vivo.

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. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically significant effect on diclofenac is expected in vivo.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Digoxin is renally eliminated renally via OATP4C1 and P-gp. Acalabrutinib is a weak inhibitor of P-gp in vitro. However, no clinically relevant effect is expected on digoxin.

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. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically significant effect on dihydrocodeine is expected in vivo.

Coadministration has not been studied but should be approached with caution. Diltiazem is metabolised by CYP3A4 and CYP2D6. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro, but no clinically relevant effect on diltiazem is expected in vivo. However, diltiazem is a moderate inhibitor of CYP3A4 and may increase acalabrutinib exposure. In a PBPK simulation, coadministration of acalabrutinib and diltiazem increased acalabrutinib AUC by 2.3-fold. Increased acalabrutinib concentrations may result in increased toxicity. Therefore, coadministration should be approached with caution. If coadministration is clinically necessary, the FDA product label recommends a dose reduction of acalabrutinib to 100 mg once daily. Monitor closely for acalabrutinib toxicity. Monitor acalabrutinib concentrations, if available.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Diphenhydramine is mainly metabolised by CYP2D6 and to a lesser extent by CYPs 1A2, 2C9 and 2C19. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro, but no clinically relevant effect on diphenhydramine is expected in vivo. Furthermore, diphenhydramine is a weak inhibitor of CYP2D6. Acalabrutinib is not metabolised by CYP2D6.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Dipyridamole is glucuronidated by many UGTs, specifically those of the UGT1A subfamily. Acalabrutinib does not inhibit or induce UGTs. However, coadministration is not recommended due to the increased risk of haemorrhage. If coadministration is unavoidable, monitor closely for signs of bleeding.

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. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on disopyramide is expected in vivo.

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%). Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on dolasetron is expected in vivo.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Domperidone is mainly metabolised by CYP3A4. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on domperidone is expected in vivo.

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 acalabrutinib, or to be affected by acalabrutinib.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Doxazosin is metabolised mainly by CYP3A4. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on doxazosin is expected in vivo.

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. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on doxepin is expected in vivo.

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. Acalabrutinib does not interact with the elimination of doxycycline.

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. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on dronabinol is expected in vivo.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Drospirenone is metabolised to a minor extent via CYP3A4. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on drospirenone is expected in vivo.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dulaglutide is degraded by endogenous endopeptidases. Acalabrutinib is unlikely to interfere with this metabolic pathway. 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. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on duloxetine is expected in vivo.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dutasteride is mainly metabolised by CYP3A4. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on dutasteride is expected in vivo.

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). Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on dydrogesterone is expected in vivo.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Edoxaban is partially metabolised by CYP3A4 (<10%) and is transported via P-gp. Acalabrutinib is an in vitro inhibitor and inducer of several CYP enzymes and a weak inhibitor of P-gp, but no clinically relevant effect on edoxaban is expected in vivo. However, coadministration is not recommended due to the increased risk of haemorrhage. If coadministration is unavoidable, monitor closely for signs of bleeding.

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). Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro, but no clinically significant effect on eltrombopag is expected in vivo.

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

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Enoxaparin does not undergo cytochrome metabolism but is desulphated and depolymerised in the liver, and is excreted predominantly renally. Acalabrutinib is unlikely to interfere with this metabolic or elimination pathway. However, coadministration is not recommended due to the increased risk of haemorrhage. If coadministration is unavoidable, monitor closely for signs of bleeding.

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. The role of OAT1/3 in renal secretion of angiotensin II receptor blockers appears limited, as these compounds are mostly excreted through the biliary route. Acalabrutinib does not interact with this elimination pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ertapenem is mainly eliminated by the kidneys via glomerular filtration with tubular secretion playing a minor role. Acalabrutinib does not interact with the elimination of ertapenem.

Coadministration has not been studied but should be approached with caution. Erythromycin is a substrate of CYP3A4 and P-gp. Acalabrutinib is an inhibitor and inducer of several CYP enzymes and a weak inhibitor of P-gp in vitro, but no clinically relevant effect on erythromycin is expected in vivo. However, erythromycin is an inhibitor of CYP3A4 (moderate) and P-gp. Concentrations of acalabrutinib may increase due to moderate inhibition of CYP3A4. In a PBPK simulation, coadministration of acalabrutinib and erythromycin increased acalabrutinib AUC by 2.8-fold. Increased acalabrutinib concentrations may result in increased toxicity. Therefore, coadministration should be approached with caution. If coadministration is clinically necessary, the FDA product label recommends a dose reduction of acalabrutinib to 100 mg once daily. Monitor closely for acalabrutinib toxicity. Monitor acalabrutinib concentrations, if available.

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. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on escitalopram is expected in vivo.

Coadministration has not been studied but should be avoided. Esomeprazole is metabolised by CYP2C19 and CYP3A4. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro, but no clinically relevant effect on esomeprazole is expected in vivo. Esomeprazole is also an inhibitor of CYP2C19. Acalabrutinib is not metabolised by CYP2C19. However, the solubility of acalabrutinib decreases with increasing pH of the stomach. In healthy volunteers, coadministration of acalabrutinib and the antacid, calcium carbonate, decreased acalabrutinib AUC and Cmax by 53% and 75%, respectively. In the same study, coadministration of acalabrutinib and the proton pump inhibitor, omeprazole, decreased acalabrutinib AUC and Cmax by 57% and 79%, respectively. A similar effect may occur with esomeprazole. Due to the long lasting effect of esomeprazole, separation of doses may not eliminate an interaction with acalabrutinib. If coadministration with a gastric acid reducing agent is clinically necessary, consider using an antacid (calcium carbonate). If administration of an antacid is clinically necessary, separate dosing by at least 2 hours to minimize a potential interaction. Monitoring of acalabrutinib efficacy is recommended.

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. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on estazolam is expected in vivo.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Estradiol is metabolised by CYP3A4, CYP1A2 and is glucuronidated. Acalabrutinib does not inhibit or induce UGTs, but is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on estradiol is expected in vivo.

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%), possibly via OCT2. Acalabrutinib does not interact with elimination pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ethinylestradiol undergoes oxidation (CYP3A4>CYP2C9), sulfation and glucuronidation (UGT1A1). Acalabrutinib does not inhibit or induce UGTs, but is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on ethinylestradiol is expected in vivo.

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. Acalabrutinib does not interfere with this metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Etonogestrel is metabolised by CYP3A4. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on etonogestrel is expected in vivo.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Everolimus is mainly metabolised by CYP3A4 and is a substrate of P-gp. Acalabrutinib is an inhibitor and inducer of several CYP enzymes and P-gp in vitro, but no clinically relevant effect on everolimus is expected in vivo. 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. Exenatide is cleared mainly by glomerular filtration. Acalabrutinib is unlikely to interfere with this elimination pathway. 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. Acalabrutinib does not inhibit or induce UGTs.

Coadministration has not been studied but should be avoided. Famotidine is excreted via OAT1/OAT3. Acalabrutinib does not inhibit or induce OATs. However, the solubility of acalabrutinib decreases with increasing pH of the stomach. In healthy volunteers, coadministration of acalabrutinib and the antacid, calcium carbonate, decreased acalabrutinib AUC and Cmax by 53% and 75%, respectively. In the same study, coadministration of acalabrutinib and the proton pump inhibitor, omeprazole, decreased acalabrutinib AUC and Cmax by 57% and 79%, respectively. A similar effect may occur with famotidine. Due to the bi-daily regimen of acalabrutinib and the lasting effect of H2 receptor antagonists, separation of doses may not eliminate an interaction with acalabrutinib. If coadministration with a gastric acid reducing agent is clinically necessary, consider using an antacid (calcium carbonate). If administration of an antacid is clinically necessary, separate dosing by at least 2 hours to minimize a potential interaction. Monitoring of acalabrutinib efficacy is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Felodipine is metabolised by CYP3A4. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on felodipine is expected in vivo.

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. Acalabrutinib does not interact with this metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fentanyl undergoes extensive CYP3A4 metabolism. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically significant effect on fentanyl is expected in vivo.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fexofenadine is a substrate of P-gp. Acalabrutinib does not inhibit or induce P-gp.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Finasteride is metabolised by CYP3A4. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on finasteride is expected in vivo.

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 eliminated unchanged renally. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically significant effect on flecainide is expected in vivo.

Coadministration has not been studied but care should be taken. Flucloxacillin is mainly renally eliminated partly by glomerular filtration and partly by active secretion via OAT1. Acalabrutinib does not interfere with this elimination pathway. Flucloxacillin has been described as a CYP3A4 inducer but the mechanism and clinical relevance of this interaction is unknown. Concentrations of acalabrutinib may decrease due to induction of CYP3A4. Monitoring of acalabrutinib efficacy may be required.

Coadministration has not been studied. Fluconazole is cleared primarily by renal excretion. Acalabrutinib does not interfere with this elimination pathway. However, fluconazole is an inhibitor of CYPs 3A4 (moderate), 2C9 (moderate) and 2C19 (strong). Concentrations of acalabrutinib may increase due to moderate inhibition of CYP3A4. In a PBPK simulation, coadministration of acalabrutinib and fluconazole increased acalabrutinib AUC by 2.4-fold. Increased acalabrutinib concentrations may result in increased toxicity. Therefore, coadministration should be approached with caution. If coadministration is clinically necessary, the FDA product label recommends a dose reduction of acalabrutinib to 100 mg once daily. Monitor closely for acalabrutinib toxicity. Monitor acalabrutinib concentrations, if available.

Coadministration has not been studied. Flucytosine is metabolised to 5-fluorouracil (5-FU). 5-FU is further metabolised by dihydropyrimidine dehydrogenase (DPD) to an inactive metabolite. Acalabrutinib does not interfere with this elimination pathway. However, 5-FU binds to the enzyme thymidylate synthase resulting in DNA damage. This mechanism occurs in all fast dividing cells including bone marrow cells, resulting in haematological toxicity. Acalabrutinib 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. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on fludrocortisone is expected in vivo.

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. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on flunitrazepam is expected in vivo.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fluoxetine is mainly metabolised by CYP2D6 and CYP2C9, and to a lesser extent by CYP2C19 and CYP3A4 to form norfluoxetine. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro, but no clinically relevant effect on fluoxetine is expected in vivo. Furthermore, fluoxetine is a strong inhibitor of CYP2D6 and CYP2C19. Acalabrutinib is not metabolised by these CYPs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fluphenazine is metabolised by CYP2D6. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on fluphenazine is expected in vivo.

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. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on flurazepam is expected in vivo.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fluticasone is metabolised by CYP3A4. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on fluticasone is expected in vivo.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fluvastatin is mainly metabolised by CYP2C9 (75%) and to a lesser extent by CYP3A4 (20%) and CYP2C8 (5%). Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro, but no clinically relevant effect on fluvastatin is expected in vivo. Furthermore, fluvastatin is a potential inhibitor of CYP2C9. Acalabrutinib is not metabolised by CYP2C9.

Coadministration has not been studied but should be approached with caution. Fluvoxamine is metabolised mainly by CYP2D6 and to a lesser extent by CYP1A2. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro, but no clinically relevant effect on fluvoxamine is expected in vivo. Fluvoxamine is also an inhibitor of CYPs 1A2 (strong), 2C19 (strong), 3A4 (moderate), 2C9 (weak-moderate) and 2D6 (weak). Concentrations of acalabrutinib may increase due to moderate inhibition of CYP3A4. PBPK simulations with acalabrutinib and moderate CYP3A4 inhibitors resulted in an increased acalabrutinib Cmax and AUC by 2- to almost 3-fold. Increased acalabrutinib concentrations may result in increased toxicity. Coadministration should be approached with caution. If coadministration is clinically necessary, the FDA product label recommends a dose reduction of acalabrutinib to 100 mg once daily. Monitor closely for acalabrutinib toxicity. Monitor acalabrutinib concentrations, if available.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Fondaparinux does not undergo cytochrome metabolism but is eliminated predominantly renally. Acalabrutinib is unlikely to interact with this elimination pathway. However, coadministration is not recommended due to the increased risk of haemorrhage. If coadministration is unavoidable, monitor closely for signs of bleeding.

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. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on formoterol is expected in vivo.

Coadministration has not been studied but should be approached with caution. Fosaprepitant is rapidly, almost completely, converted to the active metabolite aprepitant. Acalabrutinib does not interact with this metabolic pathway. Aprepitant is mainly metabolised by CYP3A4 and to a lesser extent by CYP1A2 and CYP2C19. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro, but no clinically relevant effect on aprepitant is expected in vivo. However, during treatment aprepitant is a moderate inhibitor of CYP3A4 and may increase concentrations of acalabrutinib. Increased acalabrutinib concentrations may result in increased toxicity. Therefore, coadministration should be approached with caution. If coadministration is clinically necessary, reduce the acalabrutinib dose by 50% during the few days of coadministration. Furthermore, after treatment aprepitant is a weak inducer of CYP3A4, CYP2C9 and UGT. Concentrations of acalabrutinib may decrease due to induction of CYP3A4. However, this is not considered to be clinically relevant.

Coadministration has not been studied but should be avoided. Fosphenytoin is rapidly converted to the active metabolite phenytoin. Acalabrutinib does not interact with this pathway. Phenytoin is mainly metabolised by CYP2C9 and to a lesser extent by CYP2C19. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro, but no clinically relevant effect on phenytoin is expected in vivo. However, phenytoin is a potent inducer of CYP3A4, UGT and P-gp. Concentrations of acalabrutinib may decrease due to strong induction of CYP3A4 and P-gp. In healthy volunteers, coadministration of acalabrutinib and the strong CYP3A4 inducer, rifampicin, decreased acalabrutinib AUC and Cmax by 77% and 68%, respectively. A similar effect may occur with phenytoin. A decrease in acalabrutinib exposure may lead to decreased efficacy. Therefore, coadministration should be avoided. If coadministration is unavoidable, the FDA product label recommends increasing the acalabrutinib dose to 200 mg twice daily. Closely monitor acalabrutinib efficacy. Monitor acalabrutinib concentrations, if available.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Furosemide is glucuronidated mainly in the kidney (UGT1A9) and to a lesser extent in the liver (UGT1A1). A large proportion of furosemide is also eliminated unchanged renally (via OATs). In vitro data indicate that furosemide is an inhibitor of the renal transporters OAT1/OAT3. OAT1/3 are the major transporters of loop and thiazide diuretics. Secretion of these diuretics into the urinary tract by transporters in the proximal tubular cells is necessary for the diuretic effect in later tubule segments. Acalabrutinib does not interfere 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. Acalabrutinib 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. Gemfibrozil is metabolised by UGT2B7. Acalabrutinib does not inhibit or induce UGTs. Furthermore, gemfibrozil is an inhibitor of CYP2C8 (strong), OATP1B1 and OAT3. In vitro data indicate gemfibrozil to also be a strong inhibitor of CYP2C9 but in vivo data showed no clinically relevant effect on CYP2C9. Acalabrutinib is not a substrate of these CYPs, OATPs or OATs.

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. Acalabrutinib does not interfere with this elimination pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Gestodene is metabolised by CYP3A4 and to a lesser extent by CYP2C9 and CYP2C19. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on gestodene is expected in vivo.

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. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on glibenclamide is expected in vivo.

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. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on gliclazide is expected in vivo.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Glimepiride is mainly metabolised by CYP2C9. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on glimepiride is expected in vivo.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Glipizide is mainly metabolised by CYP2C9. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on glipizide is expected in vivo.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Granisetron is metabolised by CYP3A4 and is a substrate of P-gp. Acalabrutinib is an inhibitor and inducer of several CYP enzymes and a weak inhibitor of P-gp in vitro. However, no clinically relevant effect on granisetron is expected in vivo.

Coadministration has not been studied but should be avoided. Grapefruit juice is a known inhibitor of CYP3A4 and may increase acalabrutinib concentrations. Increased acalabrutinib exposure may increase the risk of exposure-related toxicity.

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. Acalabrutinib does not interfere with this elimination pathway. However, griseofulvin is a liver microsomal enzyme inducer and may lower plasma levels, and therefore reduce the efficacy of concomitantly administered medicinal products that are metabolised by CYP3A4, such as acalabrutinib. The clinical relevance of this interaction is unknown. If coadministration is unavoidable, close monitoring is recommended.

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). Acalabrutinib does not inhibit or induce UGTs, but is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on haloperidol is expected in vivo.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Heparin is thought to be eliminated via the reticuloendothelial system. Acalabrutinib does not interact with this metabolic pathway. However, coadministration is not recommended due to the increased risk of haemorrhage. If coadministration is unavoidable, monitor closely for signs of bleeding.

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 suggest 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 acalabrutinib.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Hydrochlorothiazide is not metabolised but is cleared by the kidneys via OAT1. OAT1/3 are the major transporters of loop and thiazide diuretics. Secretion of these diuretics into the urinary tract by transporters in the proximal tubular cells is necessary for the diuretic effect in later tubule segments. Acalabrutinib does not interfere with this pathway.

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. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically significant effect on hydrocodone is expected in vivo.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Hydrocortisone is metabolised by CYP3A4. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on hydrocortisone is expected in vivo.

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. Acalabrutinib does not inhibit or induce UGTs.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Hydroxyurea is metabolised in the liver and cleared via the lungs and kidneys. Acalabrutinib does not interfere with this metabolic or elimination pathway. However, due to the risk of additive haematological toxicity, haematological parameters should be monitored if coadministered.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Hydroxyzine is partly metabolised by alcohol dehydrogenase and partly by CYP3A4. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on hydroxyzine is expected in vivo.

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. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. No clinically significant effect on ibuprofen exposure is expected in vivo. However, acalabrutinib coadministration with ibuprofen may increase the risk of haemorrhage. Therefore monitoring for bleeding may be required.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Iloperidone is metabolised by CYP3A4 and CYP2D6. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on iloperidone is expected in vivo.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Imipenem/cilastatin are eliminated by glomerular filtration and to a lesser extent by active tubular secretion via OAT3. Acalabrutinib does not interfere 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. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on imipramine is expected in vivo.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Indapamide is extensively metabolised by CYP450. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on indapamide is expected in vivo. OAT1/3 are the major transporters of loop and thiazide diuretics. Secretion of these diuretics into the urinary tract by transporters in the proximal tubular cells is necessary for the diuretic effect in later tubule segments. Acalabrutinib does not inhibit or induce OATs.

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 pharmacokinetic interaction is unlikely. Interleukin-2 is mainly eliminated by glomerular filtration. Acalabrutinib does not interfere with this elimination pathway. However, due to the risk of additive haematological toxicity, haematological parameters should be monitored if coadministered.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. A small proportion of an inhaled ipratropium dose is systemically absorbed (6.9%). Metabolism is via ester hydrolysis and conjugation. Acalabrutinib 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). Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on irbesartan is expected in vivo.

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. Acalabrutinib 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. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on isosorbide dinitrate is expected in vivo.

Coadministration should be avoided. Itraconazole is primarily metabolised by CYP3A4. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro, but no clinically relevant effect on itraconazole is expected in vivo. However, itraconazole is an inhibitor of CYP3A4 (strong), CYP2C9 (weak), P-gp and BCRP. Concentrations of acalabrutinib may increase due to strong inhibition of CYP3A4 and P-gp. In healthy volunteers, coadministration of acalabrutinib and itraconazole increased acalabrutinib AUC and Cmax by 5.1- and 3.9-fold, respectively. Increased acalabrutinib concentrations may result in increased toxicity. Therefore, coadministration should be avoided. If inhibitor use is short-term (such as anti-infectives) and cannot be avoided, withhold acalabrutinib treatment temporarily (for 7 days or less). Monitor closely for acalabrutinib toxicity.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ivabradine is metabolised by CYP3A4. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on ivabradine is expected in vivo.

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. Acalabrutinib does not interfere with this elimination pathway.

Coadministration has not been studied but should be avoided. Ketoconazole is a substrate of CYP3A4. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro, but no clinically relevant effect on ketoconazole is expected in vivo. However, ketoconazole is an inhibitor of CYP3A4 (strong) and P-gp, and may increase concentrations of acalabrutinib. In healthy volunteers, coadministration of acalabrutinib and the strong CYP3A4 inhibitor, itraconazole, increased acalabrutinib AUC and Cmax by 5.1- and 3.9-fold, respectively. A similar effect may occur with ketoconazole. Increased acalabrutinib concentrations may result in increased toxicity. Therefore, coadministration should be avoided. If inhibitor use is short-term (such as anti-infectives) and cannot be avoided, withhold acalabrutinib treatment temporarily (for 7 days or less). Monitor closely for acalabrutinib toxicity.

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). Acalabrutinib 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. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on lacidipine is expected in vivo.

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. Acalabrutinib is unlikely to interfere with this metabolic pathway.

Coadministration has not been studied but should be avoided. Lansoprazole is mainly metabolised by CYP2C19 and to a lesser extent by CYP3A4. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro, but no clinically relevant effect on lansoprazole is expected in vivo. However, the solubility of acalabrutinib decreases with increasing pH of the stomach. In healthy volunteers, coadministration of acalabrutinib and the antacid, calcium carbonate, decreased acalabrutinib AUC and Cmax by 53% and 75%, respectively. In the same study, coadministration of acalabrutinib and the proton pump inhibitor, omeprazole, decreased acalabrutinib AUC and Cmax by 57% and 79%, respectively. A similar effect may occur with lansoprazole. Due to the long lasting effect of lansoprazole, separation of doses may not eliminate an interaction with acalabrutinib. If coadministration with a gastric acid reducing agent is clinically necessary, consider using an antacid (calcium carbonate). If administration of an antacid is clinically necessary, separate dosing by at least 2 hours to minimize a potential interaction. Monitoring of acalabrutinib efficacy is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lercanidipine is mainly metabolised by CYP3A4. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on lercanidipine is expected in vivo.

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 (possibly via OCT2). Acalabrutinib 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. Levofloxacin is eliminated renally mainly by glomerular filtration and active secretion (possibly OCT2). Acalabrutinib 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. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on levomepromazine is expected in vivo.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Levonorgestrel is mainly metabolised by CYP3A4 and is glucuronidated to a minor extent. Acalabrutinib does not inhibit or induce UGTs, but is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on levonorgestrel is expected in vivo.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Levonorgestrel is mainly metabolised by CYP3A4 and is glucuronidated to a minor extent. Acalabrutinib does not inhibit or induce UGTs, but is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on levonorgestrel is expected in vivo.

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. Acalabrutinib 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. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically significant effect on lidocaine is expected in vivo.

Coadministration has not been studied but care should be taken. 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. Acalabrutinib is an inhibitor and inducer of several CYP enzymes and P-gp (weak) in vitro, but no clinically relevant effect on linagliptin is expected in vivo. However, linagliptin is a weak inhibitor of CYP3A4 and may increase concentrations of acalabrutinib. The clinical relevance of this interaction is unknown. No a priori dose adjustment is necessary. Monitoring for acalabrutinib toxicity should be considered.

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

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lisinopril is eliminated unchanged renally via glomerular filtration. Acalabrutinib 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.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Loperamide is mainly metabolised by CYP3A4 and CYP2C8, and is a substrate of P-gp. Acalabrutinib is an inhibitor and inducer of several CYP enzymes and a weak inhibitor of P-gp in vitro. However, no clinically relevant effect on loperamide is expected in vivo.

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. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on loratadine is expected in vivo.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lormetazepam is mainly glucuronidated. Acalabrutinib 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. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on losartan is expected in vivo.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lovastatin is metabolised by CYP3A4. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on lovastatin is expected in vivo.

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. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on macitentan is expected in vivo.

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. Acalabrutinib 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. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on maprotiline is expected in vivo.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Medroxyprogesterone is metabolised by CYP3A4. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on medroxyprogesterone is expected in vivo.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Medroxyprogesterone is metabolised by CYP3A4. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on medroxyprogesterone is expected in vivo.

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. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically significant effect on mefenamic acid is expected in vivo.

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. Acalabrutinib 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. Acalabrutinib 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. Acalabrutinib does not interfere with this metabolic pathway.

Coadministration has not been studied. Metamizole is metabolised by hydrolysis to the active metabolite MAA in the gastrointestinal tract. Metamizole is metabolised in serum and excreted via urine (90%) and faeces (10%). Acalabrutinib does not interact with this metabolic pathway. However, metamizole is an inducer of CYP3A4 and may decrease acalabrutinib concentrations. The clinical relevance of this interaction is unknown. A decrease in exposure may lead to decreased efficacy. Coadministration should be approached with caution. If coadministration is unavoidable, close monitoring of acalabrutinib efficacy is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metformin is mainly eliminated unchanged in the urine and is a substrate of OCT1/2/3, MATE1 and MATE2K. Acalabrutinib does not inhibit or induce these OCTs or MATEs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Methadone is demethylated by CYP3A4. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically significant effect on methadone is expected in vivo.

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 acalabrutinib or to be altered by acalabrutinib.

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. Acalabrutinib 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. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on methylprednisolone is expected in vivo.

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). Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on metoclopramide is expected in vivo.

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. OAT1/3 are the major transporters of loop and thiazide diuretics. Secretion of these diuretics into the urinary tract by transporters in the proximal tubular cells is necessary for the diuretic effect in later tubule segments. Acalabrutinib does not interfere with this elimination pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metoprolol is mainly metabolised by CYP2D6. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on metoprolol is expected in vivo.

Coadministration has not been studied but care should be taken. Metronidazole is eliminated via glomerular filtration. Acalabrutinib does not interfere with this elimination pathway. Elevated plasma concentrations have been reported for some CYP3A substrates (e.g. tacrolimus, ciclosporin) with metronidazole. However, metronidazole did not increase concentrations of several CYP3A probe drugs (e.g. midazolam, alprazolam). Since the mechanism of the interaction with CYP3A has not yet been identified, an interaction with acalabrutinib cannot be excluded. Monitoring for acalabrutinib toxicity may be required.

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. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically significant effect on mexiletine is expected in vivo.

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. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on mianserin is expected in vivo.

Coadministration has not been studied but should be avoided. Miconazole is extensively metabolised by the liver. Acalabrutinib is unlikely to interfere with this unspecified metabolic pathway. However, miconazole is an inhibitor of CYP2C9 (moderate) and CYP3A4 (strong). Concentrations of acalabrutinib may increase due to strong inhibition of CYP3A4. In healthy volunteers, coadministration of acalabrutinib and the strong CYP3A4 inhibitor, itraconazole, increased acalabrutinib AUC and Cmax by 5.1- and 3.9-fold, respectively. A similar effect may occur with miconazole. Increased acalabrutinib concentrations may result in increased toxicity. Therefore, coadministration should be avoided. If inhibitor use is short-term (such as anti-infectives) and cannot be avoided, withhold acalabrutinib treatment temporarily (for 7 days or less). Monitor closely for acalabrutinib toxicity. Dermal application: No a priori dosage adjustment is recommended for acalabrutinib, since miconazole is used topically and systemic exposure is limited.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Midazolam is metabolised by CYP3A4. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on midazolam is expected in vivo.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Midazolam is metabolised by CYP3A4. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on midazolam is expected in vivo.

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%). Acalabrutinib 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. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on mirtazapine is expected in vivo.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Mometasone is metabolised by CYP3A4. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on mometasone is expected in vivo.

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. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on montelukast is expected in vivo.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Morphine is mainly glucuronidated to morphine-3-glucuronide (UGT2B7>UGT1A1) and, to a lesser extent, to the pharmacologically active morphine-6-glucuronide (UGT2B7>UGT1A1). Morphine is also a substrate of P-gp. Acalabrutinib is a weak inhibitor of P-gp in vitro, but no clinically significant effect on morphine is expected in vivo.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Moxifloxacin is predominantly glucuronidated by UGT1A1. Acalabrutinib 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. The active metabolite of mycophenolate, mycophenolic acid, is an inhibitor of OAT1/OAT3. Acalabrutinib does not interact with this pathway. However, due to the risk of additive haematological toxicity, haematological parameters should be monitored if coadministered.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Nadroparin is renally excreted by a nonsaturable mechanism. Acalabrutinib does not interact with this elimination pathway. However, coadministration is not recommended due to the increased risk of haemorrhage. If coadministration is unavoidable, monitor closely for signs of bleeding.

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. Acalabrutinib does not interact with this metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Naproxen is mainly glucuronidated by UGT2B7 (major) and demethylated to desmethylnaproxen by CYP2C9 (major) and CYP1A2. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically significant effect on naproxen is expected in vivo.

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%). Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on nateglinide is expected in vivo.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nebivolol metabolism involves CYP2D6. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on nebivolol is expected in vivo.

Coadministration has not been studied but should be avoided. Nefazodone is metabolised mainly by CYP3A4. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro, but no clinically relevant effect on nefazodone is expected in vivo. However, nefazodone is a strong inhibitor of CYP3A4 and may increase concentrations of acalabrutinib. In healthy volunteers, coadministration of acalabrutinib and the strong CYP3A4 inhibitor, itraconazole, increased acalabrutinib AUC and Cmax by 5.1- and 3.9-fold, respectively. A similar effect may occur with nefazodone. Increased acalabrutinib concentrations may result in increased toxicity. Therefore, coadministration should be avoided. If inhibitor use is short-term (such as anti-infectives) and cannot be avoided, withhold acalabrutinib treatment temporarily (for 7 days or less). Monitor closely for acalabrutinib toxicity.

Coadministration has not been studied but care should be taken. Nicardipine is metabolised mainly by CYP3A4 and to a lesser extent by CYP2D6 and CYP2C8. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro, but no clinically relevant effect on nicardipine is expected in vivo. However, nicardipine is a weak inhibitor of CYP3A4 and may increase acalabrutinib concentrations. As the clinical relevance of this interaction is unknown, monitoring for acalabrutinib toxicity should be considered. No a priori dose adjustment is necessary.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nicotinamide is converted to N-methylnicotinamide by nicotinamide methyltransferase which in turn is metabolised by xanthine oxidase and aldehyde oxidase. Acalabrutinib 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. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on nifedipine is expected in vivo.

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. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically significant effect on nimesulide is expected in vivo.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nisoldipine is metabolised by CYP3A4. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on nisoldipine is expected in vivo.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nitrendipine is extensively metabolised mainly by CYP3A4. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on nitrendipine is expected in vivo.

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%). Acalabrutinib does not interact with the metabolism and elimination of nitrofurantoin.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Norelgestromin is metabolised to norgestrel (possibly by CYP3A4). Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on norelgestromin is expected in vivo.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Norgestimate is rapidly deacetylated to the active metabolite which is further metabolised via CYP450. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on norgestimate is expected in vivo.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Norgestrel is a racemic mixture with levonorgestrel being biologically active. Levonorgestrel is mainly metabolised by CYP3A4 and is glucuronidated to a minor extent. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on levonorgestrel is expected in vivo.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nortriptyline is metabolised mainly by CYP2D6. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on nortriptyline is expected in vivo.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ofloxacin is eliminated unchanged renally by glomerular filtration and active tubular secretion via both cationic and anionic transport systems (OAT/OCT). Acalabrutinib does not 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 (major) and CYP2D6, but also by glucuronidation (UGT1A4). Acalabrutinib does not inhibit or induce UGTs, but is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on olanzapine is expected in vivo.

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. The role of OAT1/3 in renal secretion of angiotensin II receptor blockers appears limited, as these compounds are mostly excreted through the biliary route. Acalabrutinib does not interact with this pathway.

Coadministration should be avoided. Omeprazole is mainly metabolised by CYP2C19 and to a lesser extent by CYP3A4. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro, but no clinically relevant effect on omeprazole is expected in vivo. Omeprazole is also an inducer of CYP1A2 and an inhibitor of CYP2C19. Acalabrutinib is not metabolised by CYP1A2 or CYP2C19. However, the solubility of acalabrutinib decreases with increasing pH of the stomach. In healthy volunteers, coadministration of acalabrutinib and the antacid, calcium carbonate, decreased acalabrutinib AUC and Cmax by 53% and 75%, respectively. In the same study, coadministration of acalabrutinib and omeprazole, decreased acalabrutinib AUC and Cmax by 57% and 79%, respectively. Due to the long lasting effect of omeprazole, separation of doses may not eliminate an interaction with acalabrutinib. If coadministration with a gastric acid reducing agent is clinically necessary, consider using an antacid (calcium carbonate). If administration of an antacid is clinically necessary, separate dosing by at least 2 hours to minimize a potential interaction. Monitoring of acalabrutinib efficacy is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ondansetron is metabolised mainly by CYP1A2 and CYP3A4, and to a lesser extent by CYP2D6. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on ondansetron is expected in vivo.

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

Coadministration has not been studied but should be approached with caution. Oxcarbazepine is extensively metabolised to the active metabolite monohydroxyderivate (MHD) through cystolic enzymes. Acalabrutinib 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 acalabrutinib may decrease due to moderate induction of CYP3A4. A decrease in exposure may lead to decreased efficacy. The clinical relevance of this interaction is unknown. If coadministration is unavoidable, closely monitor acalabrutinib efficacy. Monitor acalabrutinib concentrations, if available.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Oxprenolol is largely metabolised via glucuronidation. Acalabrutinib 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. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically significant effect on oxycodone is expected in vivo.

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. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on paliperidone is expected in vivo.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Palonosetron is metabolised mainly by CYP3A4 and to a lesser extent by CYP2D6 and CYP1A2. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on palonosetron is expected in vivo.

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. Acalabrutinib does not interfere with this elimination pathway.

Coadministration has not been studied but should be avoided. Pantoprazole is mainly metabolised by CYP2C19 and to a lesser extent by CYPs 3A4, 2D6 and 2C9. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro, but no clinically relevant effect on pantoprazole is expected in vivo. However, the solubility of acalabrutinib decreases with increasing pH of the stomach. In healthy volunteers, coadministration of acalabrutinib and the antacid, calcium carbonate, decreased acalabrutinib AUC and Cmax by 53% and 75%, respectively. In the same study, coadministration of acalabrutinib and the proton pump inhibitor, omeprazole, decreased acalabrutinib AUC and Cmax by 57% and 79%, respectively. A similar effect may occur with pantoprazole. Due to the long lasting effect of pantoprazole, separation of doses may not eliminate an interaction with acalabrutinib. If coadministration with a gastric acid reducing agent is clinically necessary, consider using an antacid (calcium carbonate). If administration of an antacid is clinically necessary, separate dosing by at least 2 hours to minimize a potential interaction. Monitoring of acalabrutinib efficacy is recommended.

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. Acalabrutinib does not interfere with this elimination pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Paracetamol is mainly metabolised by glucuronidation (via UGTs 1A9 (major), 1A6, 1A1 and 2B15), sulfation, and to a lesser extent, by oxidation (CYPs 2E1 (major), 1A2, 3A4 and 2D6). Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically significant effect on paracetamol is expected in vivo.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Paroxetine is mainly metabolised by CYP2D6. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro, but no clinically relevant effect on paroxetine is expected in vivo. Furthermore, paroxetine is an inhibitor of CYP2D6 (strong) and CYP2C9. Acalabrutinib is not metabolised by these 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). Acalabrutinib does not interfere with this elimination pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Perazine is mainly metabolised by CYPs 1A2, 3A4 and 2C19, and to a lesser extent by CYPs 2C9, 2D6 and 2E1, with oxidation via FMO3. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on perazine is expected in vivo.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. The metabolism of periciazine has not been well characterised but is likely to involve CYP2D6. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on periciazine is expected in vivo.

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 (possibly via OAT). Acalabrutinib 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. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on perphenazine is expected in vivo.

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. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically significant effect on pethidine is expected in vivo.

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. Acalabrutinib is unlikely to interfere with this 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. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro, but no clinically relevant effect on phenobarbital is expected in vivo. However, phenobarbital is a strong inducer of CYPs 3A4, 2C9, 2C8 and UGTs. Concentrations of acalabrutinib may decrease due to strong induction of CYP3A4. In healthy volunteers, coadministration of acalabrutinib and the strong CYP3A4 inducer, rifampicin, decreased acalabrutinib AUC and Cmax by 77% and 68%, respectively. A similar effect may occur with phenobarbital. A decrease in acalabrutinib exposure may lead to decreased efficacy. Therefore, coadministration should be avoided. If coadministration is unavoidable, the FDA product label recommends increasing the acalabrutinib dose to 200 mg twice daily. Closely monitor acalabrutinib efficacy. Monitor acalabrutinib concentrations, if available.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Phenprocoumon is mainly metabolised by CYP2C9 and CYP3A4. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro, but no clinically significant effect on phenprocoumon is expected in vivo. However, coadministration is not recommended due to the increased risk of haemorrhage. If coadministration is unavoidable, monitor closely for signs of bleeding.

Coadministration has not been studied but should be avoided. Phenytoin is mainly metabolised by CYP2C9 and to a lesser extent by CYP2C19. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro, but no clinically relevant effect on phenytoin is expected in vivo. However, phenytoin is a potent inducer of CYP3A4, UGT and P-gp. Concentrations of acalabrutinib may decrease due to strong induction of CYP3A4 and P-gp. In healthy volunteers, coadministration of acalabrutinib and the strong CYP3A4 inducer, rifampicin, decreased acalabrutinib AUC and Cmax by 77% and 68%, respectively. A similar effect may occur with phenytoin. A decrease in acalabrutinib exposure may lead to decreased efficacy. Therefore, coadministration should be avoided. If coadministration is unavoidable, the FDA product label recommends increasing the acalabrutinib dose to 200 mg twice daily. Closely monitor acalabrutinib efficacy. Monitor acalabrutinib concentrations, if available.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. An in vitro study found that the only CYP450 enzyme involved in phytomenadione metabolism was CYP4F2. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on phytomenadione is expected in vivo.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pimozide is mainly metabolised by CYP3A4 and CYP2D6, and to a lesser extent by CYP1A2. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on pimozide is expected in vivo.

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 (possibly via OCT2). Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on pindolol is expected in vivo.

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. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on pioglitazone is expected in vivo.

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. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on pipotiazine is expected in vivo.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Piroxicam is primarily metabolised by CYP2C9. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically significant effect on piroxicam is expected in vivo.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pitavastatin is metabolised by UGTs 1A3 and 2B7 with minimal metabolism by CYPs 2C9 and 2C8. Pitavastatin is also a substrate of OATP1B1. Acalabrutinib does not inhibit or induce UGTs or OATPs, but is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on pitavastatin is expected in vivo.

Coadministration has not been studied but should be avoided. Posaconazole is primarily metabolised by UGTs and is a substrate of P-gp. Acalabrutinib does not inhibit or induce UGTs or P-gp. However, posaconazole is a strong inhibitor of CYP3A4 and may increase concentrations of acalabrutinib. In healthy volunteers, coadministration of acalabrutinib and the strong CYP3A4 inhibitor, itraconazole, increased acalabrutinib AUC and Cmax by 5.1- and 3.9-fold, respectively. A similar effect may occur with posaconazole. Increased acalabrutinib concentrations may result in increased toxicity. Therefore, coadministration should be avoided. If inhibitor use is short-term (such as anti-infectives) and cannot be avoided, withhold acalabrutinib treatment temporarily (for 7 days or less). Monitor closely for acalabrutinib toxicity.

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

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Prasugrel is a prodrug and is converted to its active metabolite mainly by CYP3A4 and CYP2B6 and to a lesser extent by CYP2C9 and CYP2C19. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro, but no clinically significant effect on prasugrel is expected in vivo. However, coadministration is not recommended due to the increased risk of haemorrhage. If coadministration is unavoidable, monitor closely for signs of bleeding.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pravastatin is minimally metabolised via CYP enzymes and is a substrate of OATP1B1. Acalabrutinib does not inhibit or induce OATPs, but is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on pravastatin is expected in vivo.

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. Acalabrutinib 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. Prednisolone undergoes hepatic metabolism via CYP3A4. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on prednisolone is expected in vivo.

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. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on prednisolone is expected in vivo.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pregabalin is cleared mainly by glomerular filtration (90% as unchanged drug). Acalabrutinib 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. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on prochlorperazine is expected in vivo.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Promethazine is metabolised by CYP2D6. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on promethazine is expected in vivo.

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. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically significant effect on propafenone is expected in vivo.

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). Acalabrutinib does not inhibit or induce UGTs, but is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on propranolol is expected in vivo.

Coadministration has not been studied but based on metabolism and clearance clinically significant interaction is unlikely. Prucalopride is minimally metabolised and mainly eliminated renally, partly by active secretion by renal transporters. Prucalopride is also a substrate of P-gp. Acalabrutinib is an inhibitor and inducer of several CYP enzymes and a weak inhibitor of P-gp in vitro. However, no clinically relevant effect on prucalopride is expected in vivo.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pyrazinamide is mainly metabolised by xanthine oxidase. Acalabrutinib 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. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on quetiapine is expected in vivo.

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. Acalabrutinib does not interact with this elimination pathway.

Coadministration has not been studied. Quinidine is mainly metabolised by CYP3A4 and to a lesser extent by CYP2C9 and CYP2E1. Quinidine is also a substrate of P-gp. Acalabrutinib is an inhibitor and inducer of several CYP enzymes and a weak inhibitor of P-gp in vitro. However, no clinically significant effect on quinidine is expected in vivo. However, quinidine is an inhibitor of CYP2D6 (strong), CYP3A4 (weak) and P-gp (moderate). Concentrations of acalabrutinib may increase due to inhibition of CYP3A4 and P-gp. As the clinical relevance of this interaction is unknown, monitoring for acalabrutinib toxicity should be considered. No a priori dose adjustment is necessary.

Coadministration has not been studied but should be avoided. Rabeprazole is mainly metabolised via non-enzymatic reduction and to a lesser extent by CYP2C19 and CYP3A4. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro, but no clinically relevant effect on rabeprazole is expected in vivo. However, the solubility of acalabrutinib decreases with increasing pH of the stomach. In healthy volunteers, coadministration of acalabrutinib and the antacid, calcium carbonate, decreased acalabrutinib AUC and Cmax by 53% and 75%, respectively. In the same study, coadministration of acalabrutinib and the proton pump inhibitor, omeprazole, decreased acalabrutinib AUC and Cmax by 57% and 79%, respectively. A similar effect may occur with rabeprazole. Due to the long lasting effect of rabeprazole, separation of doses may not eliminate an interaction with acalabrutinib. If coadministration with a gastric acid reducing agent is clinically necessary, consider using an antacid (calcium carbonate). If administration of an antacid is clinically necessary, separate dosing by at least 2 hours to minimize a potential interaction. Monitoring of acalabrutinib efficacy is recommended.

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. Acalabrutinib is not expected to interfere with these metabolic pathways.

Coadministration has not been studied but should be avoided. Ranitidine is excreted via OAT1/OAT3. Acalabrutinib does not inhibit or induce OATs. However, the solubility of acalabrutinib decreases with increasing pH of the stomach. In healthy volunteers, coadministration of acalabrutinib and the antacid, calcium carbonate, decreased acalabrutinib AUC and Cmax by 53% and 75%, respectively. In the same study, coadministration of acalabrutinib and the proton pump inhibitor, omeprazole, decreased acalabrutinib AUC and Cmax by 57% and 79%, respectively. A similar effect may occur with ranitidine. Due to the bi-daily regimen of acalabrutinib and the lasting effect of H2 receptor antagonists, separation of doses may not eliminate an interaction with acalabrutinib. If coadministration with a gastric acid reducing agent is clinically necessary, consider using an antacid (calcium carbonate). If administration of an antacid is clinically necessary, separate dosing by at least 2 hours to minimize a potential interaction. Monitoring of acalabrutinib efficacy is recommended.

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. Acalabrutinib is an inhibitor and inducer of several CYP enzymes and P-gp in vitro, but no clinically relevant effect on ranolazine is expected in vivo. However, ranolazine is a weak inhibitor of P-gp, CYP3A4 and CYP2D6. Concentrations of acalabrutinib may increase due to weak inhibition of CYP3A4. As the clinical relevance of this interaction is unknown, monitoring for acalabrutinib toxicity should be considered. No a priori dose adjustment is necessary.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Reboxetine is metabolised by CYP3A4. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro, but no clinically relevant effect on reboxetine is expected in vivo. Furthermore, in vitro data indicate reboxetine to be a weak inhibitor of CYP3A4 but in vivo data showed no inhibitory effect on CYP3A4. Although acalabrutinib is a substrate of CYP3A4, a clinically relevant interaction is unlikely.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Repaglinide is metabolised by CYP2C8 and CYP3A4 with clinical data indicating it is a substrate of OATP1B1. Acalabrutinib does not inhibit or induce OATP1B1, but is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on repaglinide is expected in vivo.

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. Acalabrutinib 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. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro, but no clinically relevant effect on rifabutin is expected in vivo. However, rifabutin is a strong CYP3A4 and P-gp inducer. Concentrations of acalabrutinib may decrease due to strong CYP3A4 induction. In healthy volunteers, coadministration of acalabrutinib and the strong CYP3A4 inducer, rifampicin decreased acalabrutinib AUC and Cmax by 77% and 68%, respectively. A similar effect may occur with rifabutin. A decrease in acalabrutinib exposure may lead to decreased efficacy. Therefore, coadministration should be avoided. If coadministration is unavoidable, the FDA product label recommends increasing the acalabrutinib dose to 200 mg twice daily. Closely monitor acalabrutinib efficacy. Monitor acalabrutinib concentrations, if available.

Coadministration should be avoided. Rifampicin is metabolised via deacetylation. Acalabrutinib does not interact with this metabolic pathway. However, rifampicin is a strong CYP3A4 and P-gp inducer. Concentrations of acalabrutinib may significantly decrease due to induction of CYP3A4. In healthy volunteers, coadministration of acalabrutinib and rifampicin decreased acalabrutinib AUC and Cmax by 77% and 68%, respectively. A decrease in acalabrutinib exposure may lead to decreased efficacy. Therefore, coadministration should be avoided. If coadministration is unavoidable, the FDA product label recommends increasing the acalabrutinib dose to 200 mg twice daily. Closely monitor acalabrutinib efficacy. Monitor acalabrutinib concentrations, if available.

Coadministration has not been studied but should be avoided. Rifapentine is metabolised via deacetylation. Acalabrutinib does not interact with this metabolic pathway. However, rifapentine is a strong CYP3A4, CYP2C8 and P-gp inducer. Concentrations of acalabrutinib may decrease due to induction of CYP3A4. In healthy volunteers, coadministration of acalabrutinib and the strong CYP3A4 inducer, rifampicin, decreased acalabrutinib AUC and Cmax by 77% and 68%, respectively. A similar effect may occur with rifapentine. A decrease in acalabrutinib exposure may lead to decreased efficacy. Therefore, coadministration should be avoided. If coadministration is unavoidable, the FDA product label recommends increasing the acalabrutinib dose to 200 mg twice daily. Closely monitor acalabrutinib efficacy. Monitor acalabrutinib concentrations, if available.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Risperidone is metabolised by CYP2D6 and to a lesser extent by CYP3A4. Risperidone is also a substrate of P-gp. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro and a weak inhibitor of P-gp in vitro. However, no clinically relevant effect on risperidone is expected in vivo.

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. Acalabrutinib is an in vitro inhibitor and inducer of several CYP enzymes and a weak inhibitor of P-gp, but no clinically relevant effect on rivaroxaban is expected in vivo. However, acalabrutinib is an inhibitor of BCRP in the gastrointestinal tract and may increase concentrations of rivaroxaban. The clinical relevance of this interaction is unknown. Monitoring for signs and symptoms of rivaroxaban toxicity is recommended. Furthermore, coadministration may increase the risk of haemorrhage. If coadministration is unavoidable, monitor closely for signs of bleeding.

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. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on rosiglitazone is expected in vivo.

Coadministration has not been studied. Rosuvastatin is largely excreted unchanged via the faeces via OATP1B1. Rosuvastatin is also a substrate of BCRP. Acalabrutinib is an inhibitor of BCRP and may increase the exposure to rosuvastatin the gastrointestinal tract. As the clinical relevance of this interaction is unknown, monitoring for signs and symptoms of rosuvastatin toxicity may be necessary.

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. Acalabrutinib does not interact with this metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Systemic exposure of salmeterol is low but salmeterol is metabolised by CYP3A4. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on salmeterol is expected in vivo.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Saxagliptin is mainly metabolised by CYP3A4 and is a substrate of P-gp. Acalabrutinib is an inhibitor and inducer of several CYP enzymes and P-gp (weak) in vitro. However, no clinically relevant effect on saxagliptin is expected in vivo.

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. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on sertindole is expected in vivo.

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. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro, but no clinically relevant effect on sertraline is expected in vivo.

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. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on sildenafil is expected in vivo.

Coadministration has not been studied. Simvastatin is metabolised by CYP3A4 and the active metabolite is a substrate of OATP1B1. Simvastatin is also a substrate of BCRP. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro, but no clinically relevant effect on simvastatin is expected in vivo. However, acalabrutinib is also an inhibitor of BCRP and may increase exposure to simvastatin in the gastrointestinal tract. As the clinical relevance of this interaction is unknown, monitoring for signs and symptoms of simvastatin toxicity may be necessary.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Sirolimus is metabolised by CYP3A4 and is a substrate of P-gp. Acalabrutinib is an inhibitor and inducer of several CYP enzymes and P-gp in vitro, but no clinically relevant effect on sirolimus is expected in vivo. 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. Sitagliptin is primarily eliminated in urine as unchanged drug (active secretion by OAT3, OATP4C1 and P-gp) and metabolism by CYP3A4 represents a minor metabolic pathway. Acalabrutinib is an inhibitor and inducer of several CYP enzymes and P-gp (weak) in vitro. However, no clinically relevant effect on sitagliptin is expected in vivo.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Sotalol is excreted unchanged via renal elimination (possibly via OCT). Acalabrutinib is not expected to interfere 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. Acalabrutinib does not interact with this metabolic pathway.

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

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

Coadministration has not been studied but should be avoided. St John’s Wort is a strong inducer of CYP3A4 and P-gp, and may significantly decrease acalabrutinib concentrations. Decreased acalabrutinib exposure may lead to reduced efficacy.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic 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 acalabrutinib, or to be affected if co-administered with acalabrutinib. However, coadministration is not recommended due to the increased risk of haemorrhage. If coadministration is unavoidable, monitor closely for signs of bleeding.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Streptomycin is eliminated by glomerular filtration. Acalabrutinib 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. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically significant effect on sulfadiazine is expected in vivo.

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. Acalabrutinib does not interfere with this elimination pathway.

Coadministration has not been studied. Tacrolimus is metabolised mainly by CYP3A4. Acalabrutinib is an inhibitor and inducer of several CYP enzymes and P-gp in vitro, but no clinically relevant effect on tacrolimus is expected in vivo. 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. 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. Tadalafil is metabolised by CYP3A4. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on tadalafil is expected in vivo.

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. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on tamsulosin is expected in vivo.

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. Acalabrutinib does not interfere 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. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro, but no clinically relevant effect on sulfadiazine is expected in vivo. However, telithromycin is an inhibitor of CYP3A4 (strong) and P-gp and may increase concentrations of acalabrutinib. In healthy volunteers, coadministration of acalabrutinib and the strong CYP3A4 inhibitor, itraconazole, increased acalabrutinib AUC and Cmax by 5.1- and 3.9-fold, respectively. A similar effect may occur with telithromycin. Increased acalabrutinib concentrations may result in increased toxicity. Therefore, coadministration should be avoided. If inhibitor use is short-term (such as anti-infectives) and cannot be avoided, withhold acalabrutinib treatment temporarily (for 7 days or less). Monitor closely for acalabrutinib toxicity.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Telmisartan is mainly glucuronidated by UGT1A3. Acalabrutinib 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. Acalabrutinib 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 CYP2C8 and CYP2C19. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on terbinafine is expected in vivo.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Testosterone is metabolised by CYP3A4. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on testosterone is expected in vivo.

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. Acalabrutinib does not interact with this pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Theophylline is mainly metabolised by CYP1A2. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on theophylline is expected in vivo.

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. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on thioridazine is expected in vivo.

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

Coadministration has not been studied. Ticagrelor is a substrate of CYP3A4 and P-gp. Acalabrutinib is an in vitro inhibitor and inducer of several CYP enzymes and a weak inhibitor of P-gp, but no clinically relevant effect on ticagrelor is expected in vivo. However, ticagrelor is a weak inhibitor of CYP3A4 and may increase concentrations of acalabrutinib. As the clinical relevance of this interaction is unknown, monitoring for acalabrutinib toxicity should be considered. No a priori dose adjustment is necessary. Furthermore, coadministration may increase the risk of haemorrhage. If coadministration is unavoidable, monitor closely for signs of bleeding.

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. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on timolol is expected in vivo. Note: the systemic absorption of timolol after ocular administration is low. Therefore, a clinically relevant interaction via CYP2D6 is unlikely.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Tinzaparin is renally excreted as unchanged or almost unchanged drug. Acalabrutinib does not interact with this elimination pathway. However, coadminstration may increase the risk of haemorrhage. If coadministration is unavoidable, monitor closely for signs of bleeding.

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. Acalabrutinib is an inhibitor and inducer of several CYP enzymes in vitro. However, no clinically relevant effect on tolbutamide is expected in vivo.