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\begin{document}

\title{Interactions between hormonal contraception and single or intermittently
dosed rifampicin: a pharmacokinetic modelling and simulation study}



\author[1]{Jeremy Hill}%
\author[2]{Kendra Radtke}%
\author[3]{Anne Schoenmakers}%
\author[1]{Christiaan Mulder}%
\author[1]{Emmy van der Grinten}%
\author[3]{Floor Overbeek}%
\author[4]{Nicole Salazar-Austin}%
\author[5]{Wilcare de Medeiros Cordeiro Nascimento}%
\author[3]{Wim van Brakel}%
\author[4]{Ethel Weld}%
\affil[1]{KNCV Tuberculosis Foundation}%
\affil[2]{University of California San Francisco}%
\affil[3]{NLR}%
\affil[4]{Johns Hopkins University School of Medicine}%
\affil[5]{Erasmus University Rotterdam}%


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  \date{May 26, 2024}


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\selectlanguage{english}
\begin{abstract}
Aim 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 who are
eligible for rifampicin-based regimens rely on OCP for family planning,
additional information characterising the interaction would enhance
scalability and acceptability of leprosy prophylaxis. Methods We used a
semi-mechanistic pharmacokinetic model to predict the expected induction
effect of rifampicin on OCP oral clearance (CL/F) when used for leprosy
prophylaxis. Rifampicin dosing schedules were selected based on
WHO-recommended and investigational leprosy prophylaxis regimens.
Uncertainty in the model was explored using a scenario analysis. Results
Hormonal contraceptive CL/F with rifampicin given as a single 600mg
dose, a single 1200mg dose, or as 600mg once every four weeks was
predicted to increase by a maximum of 12\%, 14\% and 14\%, respectively,
and return to baseline before the next dose. Hormonal contraceptive CL/F
was predicted to increase by \textgreater{}20\% with once-weekly and
once-daily dosing of 600mg rifampicin. Using a threshold of 20\%,
rifampicin used for leprosy prophylaxis does not have a clinically
relevant interaction with OCP. Conclusion These modelling study findings
suggest that women using OCP can expect efficacy to be maintained with
coadministration of rifampicin-based leprosy prophylaxis and should
provide reassurance to stakeholders that leprosy prophylaxis need not be
accompanied by any additional specific recommendation about use of OCP.%
\end{abstract}%



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