Drug Interactions between acalabrutinib and Digestive Advantage Daily Probiotic

ADJUST DOSING INTERVAL: Coadministration of acalabrutinib in its capsule formulation with drugs that increase gastric pH may significantly decrease the oral bioavailability of acalabrutinib and reduce its concentrations in plasma. The solubility of acalabrutinib is pH-dependent and decreases with increasing pH. According to the product labeling, acalabrutinib is freely soluble in water at pH below 3 and practically insoluble at pH above 6. Coadministration of acalabrutinib capsules with an antacid (1 gram calcium carbonate) decreased acalabrutinib systemic exposure (AUC) by 53% in healthy subjects, and coadministration with a proton pump inhibitor (omeprazole 40 mg for 5 days) decreased acalabrutinib AUC by 43%. Due to the long-lasting effect of proton pump inhibitors, separation of dosing may not eliminate the interaction with acalabrutinib capsules. By contrast, no clinically significant differences in the pharmacokinetics of acalabrutinib were observed when the tablet formulation, which contains acalabrutinib maleate, was coadministered with the proton pump inhibitor, rabeprazole.

MANAGEMENT: No adjustments to therapy are required when using the tablet formulation containing acalabrutinib maleate. However, if gastric acid reducing agents are required during treatment with acalabrutinib capsules, H2-receptor antagonists and/or antacids should be considered. The manufacturer recommends taking acalabrutinib 2 hours before (or 10 hours after) H2-receptor antagonists and separating the dosing with antacids by at least 2 hours.

MONITOR: Probiotic use during immunosuppressant or intense antineoplastic therapy may theoretically increase the risk of infections from the live microorganisms contained in probiotic products. Patients may be immunosuppressed if they have recently received or are receiving alkylating agents, antimetabolites, radiation, some antirheumatic agents, high dosages of corticosteroids or adrenocorticotropic agents, or long-term topical or inhaled corticosteroids. Although probiotics are generally considered safe, with minimal to low pathogenicity, infections such as bacteremia and endocarditis with various strains commonly found in probiotics (e.g., lactobacilli, bifidobacteria, Bacillus subtilis) have been rarely reported, primarily in critically ill patients or patients with significant underlying medical conditions such as malignancy, organ transplantation, AIDS, valvular heart disease, diabetes mellitus, recent surgery, or compromised immune system. Lactobacillus bacteremia has also been reported following endoscopy. In addition, cases of lactobacillus pneumonia and liver abscess, as well as Saccharomyces fungemia, pneumonia, liver abscess, peritonitis and vaginitis, have been described in the medical literature.

MANAGEMENT: Caution is advised when probiotics are used during immunosuppressant or intense antineoplastic therapy. It may be advisable to avoid using probiotics, particularly products containing saccharomyces boulardii, in patients who are significantly immunosuppressed unless benefits are anticipated to outweigh the potential risk of infection.