Coadministration of famotidine 40 mg did not affect the pharmacokinetics of apixaban 10 mg, with ratios of geometric means for Cmax (0.978) and AUC∞ (1.007) within the no-effect interval.
RCT (n=18)
two-period, two-treatment crossover
Does famotidine affect the pharmacokinetics of apixaban in healthy subjects?
Famotidine does not affect the pharmacokinetics of apixaban, indicating that apixaban can be administered without regard to coadministration of gastric acid modifiers.
Estimación del efecto: Ratio of geometric means 0.978 for Cmax and 1.007 for AUC∞
BACKGROUND: Apixaban is an oral, selective, direct factor Xa inhibitor approved for thromboprophylaxis after orthopedic surgery and stroke prevention in patients with atrial fibrillation, and under development for treatment of venous thromboembolism. This study investigated the effect of a gastric acid suppressant, famotidine (a histamine H2-receptor antagonist), on the pharmacokinetics of apixaban in healthy subjects. METHODS: This two-period, two-treatment crossover study randomized 18 healthy subjects to receive a single oral dose of apixaban 10 mg with and without a single oral dose of famotidine 40 mg administered 3 hours before dosing with apixaban. Plasma apixaban concentrations were measured up to 60 hours post-dose and pharmacokinetic parameters were calculated. RESULTS: Famotidine did not affect maximum apixaban plasma concentration (Cmax) or area under the plasma concentration-time curve from zero to infinite time (AUC∞). Point estimates for ratios of geometric means with and without famotidine were close to unity for Cmax (0.978) and AUC∞ (1.007), and 90% confidence intervals were entirely contained within the 80%-125% no-effect interval. Administration of apixaban alone and with famotidine was well tolerated. CONCLUSION: Famotidine does not affect the pharmacokinetics of apixaban, consistent with the physicochemical properties of apixaban (lack of an ionizable group and pH-independent solubility). Apixaban pharmacokinetics would not be affected by an increase in gastrointestinal pH due to underlying conditions (eg, achlorhydria), or by gastrointestinal pH-mediated effects of other histamine H2-receptor antagonists, antacids, or proton pump inhibitors. Given that famotidine is also an inhibitor of the human organic cation transporter (hOCT), these results indicate that apixaban pharmacokinetics are not influenced by hOCT uptake transporter inhibitors. Overall, these results support that apixaban can be administered without regard to coadministration of gastric acid modifiers.
Upreti et al. (Mon,) conducted a rct in healthy subjects (n=18). Famotidine vs. Apixaban 10 mg alone was evaluated on Maximum apixaban plasma concentration (Cmax) and area under the plasma concentration-time curve from zero to infinite time (AUC∞) (Ratio of geometric means 0.978 for Cmax and 1.007 for AUC∞). Coadministration of famotidine 40 mg did not affect the pharmacokinetics of apixaban 10 mg, with ratios of geometric means for Cmax (0.978) and AUC∞ (1.007) within the no-effect interval.