Effect of Activated Charcoal on Apixaban Pharmacokinetics in Healthy Subjects

BACKGROUND: Activated charcoal is commonly used to manage overdose or accidental ingestion of medicines. This study evaluated the effect of activated charcoal on apixaban exposure in human subjects. METHODS: This was an open-label, three-treatment, three-period, randomized, crossover study of single-dose apixaban (20 mg) administered alone and with activated charcoal given at 2 or 6 h post-dose to healthy subjects. Blood samples for assay of plasma apixaban concentration were collected up to 72 h post-dose. Pharmacokinetic parameters, including peak plasma concentration (C (max)), time to C (max) (T (max)), area under the concentration–time curve from time 0 to infinity (AUC(INF)), and terminal half-life (T (½)), were derived from apixaban plasma concentration–time data. A general linear mixed-effect model analysis of C (max) and AUC(INF) was performed to estimate the effect of activated charcoal on apixaban exposure. RESULTS: A total of 18 subjects were treated and completed the study. AUC(INF) for apixaban without activated charcoal decreased by 50 and 28 %, respectively, when charcoal was administered at 2 and 6 h post-dose. Apixaban C (max) and T (max) were similar across treatments. The mean T (½) for apixaban alone (13.4 h) decreased to ~5 h when activated charcoal was administered at 2 or 6 h post-dose. Overall, apixaban was well tolerated in this healthy population, and most adverse events were consistent with the known profile of activated charcoal. CONCLUSION: Administration of activated charcoal up to 6 h after apixaban reduced apixaban exposure and facilitated the elimination of apixaban. These results suggest that activated charcoal may be useful in the management of apixaban overdose or accidental ingestion.