Predicted Pharmacokinetic Interactions Between Hormonal Contraception and Single or Intermittently Dosed Rifampicin

Kendra K. Radtke*, Jeremy Hill, Anne Schoenmakers, Christiaan Mulder, Emmy van der Grinten, Floor Overbeek, Nicole Salazar-Austin, Wilcare de Medeiros Cordeiro Nascimento, Wim van Brakel, Ethel Weld

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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The 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 the effects of rifampicin at the less frequent dosing intervals used for leprosy prophylaxis. As many women of reproductive age rely on OCP for family planning, evaluating the interaction with less-than-daily rifampicin regimens would enhance the 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 (600 or 1200 mg) or 600 mg every 4 weeks was not predicted to result in a clinically relevant interaction with OCP, defined as a >25% increase in clearance. Simulations of daily rifampicin were predicted to increase OCP clearance within the range of observed changes previously reported in the literature. Therefore, our findings suggest that OCP efficacy will be maintained when coadministered with rifampicin-based leprosy prophylaxis regimens of 600 mg once, 1200 mg once, and 600 mg every 4 weeks. This work provides reassurance to stakeholders that leprosy prophylaxis can be used with OCP without any additional recommendations for contraception prevention.

Original languageEnglish
Pages (from-to)1283-1289
Number of pages7
JournalJournal of Clinical Pharmacology
Issue number11
Early online date6 Jul 2023
Publication statusPublished - Nov 2023
Externally publishedYes

Bibliographical note

Funding Information:
This work was funded by the National Institutes of Health General Medical Sciences (T32 GM007546, to K.K.R.).

Publisher Copyright:
© 2023 The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.

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