Drug Interactions between Digestive Advantage Daily Probiotic and pazopanib

GENERALLY AVOID: Coadministration with drugs that increase gastric pH may significantly decrease the oral bioavailability of pazopanib and reduce its concentrations in plasma. The solubility of pazopanib is pH-dependent, thus an increase in pH may interfere with its absorption. According to the product labeling, pazopanib is very slightly soluble at pH 1 and practically insoluble above pH 4 in aqueous media. When pazopanib (800 mg once daily in the morning) was coadministered with esomeprazole (40 mg once daily in the evening) for 5 days in 12 patients with advanced solid tumors, mean steady-state pazopanib peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by approximately 40% each. The AUCs of three metabolites were also decreased. Mean steady-state trough concentration of pazopanib was reduced to 17.3 mcg/mL, which is close to the reported threshold of >=15 mcg/mL for clinical efficacy as suggested by a phase I trial of pazopanib. However, the potential for subtherapeutic pazopanib exposure in some patients cannot be excluded.

MANAGEMENT: Concomitant use of pazopanib with drugs that increase gastric pH should generally be avoided. If acid-suppression therapy is required, short-acting antacids should be considered, with dosing separated by several hours from pazopanib dosing. Some experts recommend administering pazopanib at least 1 hour before or 2 hours after antacids.

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.