Predicted pharmacokinetic interactions between hormonal contraception and single or intermittently dosed rifampicin

Scale up of rifampicin-based prevention regimens is an essential part of the global leprosy strategy. Daily rifampicin may reduce the effectiveness of the oral contraceptive pill (OCP), but little is known about rifampicin's effects at the less frequent dosing intervals used for leprosy prophylaxis. Since many women of reproductive age rely on OCP for family planning, evaluating the interaction with less-than-daily rifampicin regimens would enhance scalability and acceptability of leprosy prophylaxis. Using a semi-mechanistic pharmacokinetic model of rifampicin induction, we simulated predicted changes in OCP clearance when coadministered with varying rifampicin dosing schedules. Rifampicin given as a single dose (600mg or 1200mg) or 600mg every 4 weeks was not predicted to result in a clinically relevant interaction with OCP, defined as >25% increase in clearance. Simulations of daily rifampicin were predicted to increase OCP clearance within the range of observed changes previously reported in literature. Therefore, our findings suggest that OCP efficacy will be maintained when coadministered with rifampicin-based leprosy prophylaxis regimens of 600mg once, 1200mg once, and 600mg every 4 weeks. This work provides reassurance to stakeholders that leprosy prophylaxis can be used with OCPs without any additional recommendations for contraception prevention. This article is protected by copyright. All rights reserved.