The tablet presentation of acalabrutinib has recently been added to the Pharmaceutical Benefits Scheme (PBS). Acalabrutinib is also available in a capsule and is PBS-subsidised for the treatment of relapsed or refractory chronic lymphocytic leukaemia (CLL), small lymphocytic lymphoma (SLL), and mantle cell lymphoma (MCL).
There are some significant differences between the tablet and capsule presentations. The tablets are smaller and film-coated, which may make them easier for patients to swallow. In addition, the tablets may be co-administered with gastric acid-reducing agents.
The bioavailability of acalabrutinib capsules is pH-dependent, with solubility reducing with increasing pH. Co-administration of acalabrutinib capsules with 40mg omeprazole reduced the area under the curve (AUC) by 43%. Therefore, acalabrutinib capsules are not recommended to be co-administered with proton pump inhibitors. If a gastric acid-reducing agent is required, it is recommended to use an antacid or H2 receptor antagonist and separate the dosing by at least two hours.
In contrast, the tablet presentation contains the maleate salt of acalabrutinib, which exhibits pH-independent release. The ELEVATE-PLUS study demonstrates that the tablet and capsule formulations have almost identical bioavailability. This study also suggests that proton pump inhibitors do not have a clinically relevant impact on acalabrutinib tablets. Administration of acalabrutinib tablets with rabeprazole resulted in an approximately 24% lower maximum concentration (Cmax) and a 14% higher AUC, which is not considered clinically significant.
The availability of acalabrutinib tablets may overcome some of the dosing issues associated with acalabrutinib capsules and remove the need for staggering the doses of gastric acid-lowering therapies.
|Hard gelatin capsule
|Acalabrutinib maleate monohydrate
|Acalabrutinib (free base)
|Proton pump inhibitors
|May be co-administered
|Other gastric acid-lowering agents
|May be co-administered
|Separate doses by at least 2 hours
- Calquence® (acalabrutinib (as maleate monohydrate)) Australian approved product information. Macquarie Park: AstraZeneca. Approved October 2022.
- Sharma S, Pepin X, Burri H, Zheng L, Yu T, MacArthur HL, et al. Bioequivalence and relative bioavailability studies to assess a new acalabrutinib formulation that enables coadministration with proton‐pump inhibitors. Clin Pharmacol Drug Dev. 2022; 11(11): 1294-1307.
Subscribe Knowledge Centre Updates
Enter your details to receive Knowledge Centre updates