TY - JOUR
T1 - Predicted Pharmacokinetic Interactions Between Hormonal Contraception and Single or Intermittently Dosed Rifampicin
AU - Radtke, Kendra K.
AU - Hill, Jeremy
AU - Schoenmakers, Anne
AU - Mulder, Christiaan
AU - van der Grinten, Emmy
AU - Overbeek, Floor
AU - Salazar-Austin, Nicole
AU - de Medeiros Cordeiro Nascimento, Wilcare
AU - van Brakel, Wim
AU - Weld, Ethel
N1 - 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.
PY - 2023/11
Y1 - 2023/11
N2 - 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.
AB - 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.
KW - contraception
KW - drug–drug interactions
KW - leprosy
KW - pharmacokinetics
KW - rifampicin
UR - http://www.scopus.com/inward/record.url?scp=85165515232&partnerID=8YFLogxK
U2 - https://doi.org/10.1002/jcph.2303
DO - https://doi.org/10.1002/jcph.2303
M3 - Article
C2 - 37409982
SN - 0091-2700
VL - 63
SP - 1283
EP - 1289
JO - Journal of clinical pharmacology
JF - Journal of clinical pharmacology
IS - 11
ER -