Food Type, Timing Has No Clinically Relevant Impact on Rivaroxaban
Findings from a cross-study analysis of rivaroxaban (Xarelto; Janssen) indicate that neither the timing nor the content of a meal seem to clinically impact the pharmacokinetics (PK) of the drug. The full study has been published in The Journal of Clinical Pharmacology.
Rivaroxaban is a highly selective oral direct factor Xa inhibitor approved to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (AF), to treat deep vein thrombosis (DVT) and pulmonary embolism (PE), to reduce the risk of recurrent DVT/PE, and for DVT prophylaxis which may lead to PE in patients undergoing knee or hip replacement surgery.
Previous well-controlled bioavailability studies have demonstrated nearly complete oral absorption of the 10mg tablet in both fed and fasting conditions. The oral bioavailability of the 20mg tablet has been reported to be ~66% under fasting conditions but almost complete under fed conditions. Currently, the prescribing information recommends 20mg once daily with an evening meal for the AF indication, and 15mg twice daily with food for 21 days, followed by 20mg once daily with food for the remainder of treatment for the DVT/PE indications.
"Given the different recommendations regarding food intake across these two indications, it is of interest to study the impact of meal timing and meal content on the PK of rivaroxaban," explained lead author Liping Zhang, PhD.
A joint PK model was used to estimate the bioavailability of rivaroxaban administered with a morning meal (DVT data) to rivaroxaban administered with an evening meal (AF data). The difference was found to be within the bioequivalence limits (80–125%), suggesting that bioavailability under both of these conditions can be considered equivalent.
Regarding the impact of meal type on rivaroxaban, researchers analyzed previously published food-effect studies that compared a standard high-calorie, high-fat breakfast (based on the Guidance for Industry), a high-carbohydrate breakfast, or applesauce with a low-calorie liquid meal. Results indicated that systemic exposure to rivaroxaban 20mg "was fairly consistent" for the varied meal types.
An indirect comparison of real-world studies (having varied meal content and timing) against Phase 3 studies (XANTUS, XALIA, REVISIT-US, and a post-marketing safety surveillance study) further "strengthen the position that meal type and timing do not play a significant role in successful treatment," noted Dr. Zhang.
After comparing steady-state exposures and predicted PK parameters with those seen in the DVT and AF studies, study authors concluded that the timing (morning vs. evening) or content of the meal was not found to impact the PK of rivaroxaban at the 20mg daily dose.
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