Pharmacokinetics and Safety of 3 Months of Weekly Rifapentine and Isoniazid for Tuberculosis Prevention in Pregnant Women
1
Issued Date
2022-05-01
Resource Type
ISSN
10584838
eISSN
15376591
Scopus ID
2-s2.0-85129998274
Pubmed ID
34323955
Journal Title
Clinical Infectious Diseases
Volume
74
Issue
9
Start Page
1604
End Page
1613
Rights Holder(s)
SCOPUS
Bibliographic Citation
Clinical Infectious Diseases Vol.74 No.9 (2022) , 1604-1613
Suggested Citation
Mathad J.S., Savic R., Britto P., Jayachandran P., Wiesner L., Montepiedra G., Norman J., Zhang N., Townley E., Chakhtoura N., Bradford S., Patil S., Popson S., Chipato T., Rouzier V., Langat D., Chalermchockcharoentkit A., Kamthunzi P., Gupta A., Dooley K.E. Pharmacokinetics and Safety of 3 Months of Weekly Rifapentine and Isoniazid for Tuberculosis Prevention in Pregnant Women. Clinical Infectious Diseases Vol.74 No.9 (2022) , 1604-1613. 1613. doi:10.1093/cid/ciab665 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/87314
Title
Pharmacokinetics and Safety of 3 Months of Weekly Rifapentine and Isoniazid for Tuberculosis Prevention in Pregnant Women
Author's Affiliation
Groupe d’étude Haïtien sur le Sarcome de Kaposi et les Infections Opportunistes
Siriraj Hospital
FHI 360
Frontier Science & Technology Research Foundation, Inc.
UNC Project-Malawi
Kenya Medical Research Institute
University of Zimbabwe
Harvard T.H. Chan School of Public Health
University of California, San Francisco
National Institute of Child Health and Human Development (NICHD)
National Institute of Allergy and Infectious Diseases (NIAID)
B.J. Medical College, Pune
Weill Cornell Medicine
Johns Hopkins School of Medicine
University of Cape Town
Siriraj Hospital
FHI 360
Frontier Science & Technology Research Foundation, Inc.
UNC Project-Malawi
Kenya Medical Research Institute
University of Zimbabwe
Harvard T.H. Chan School of Public Health
University of California, San Francisco
National Institute of Child Health and Human Development (NICHD)
National Institute of Allergy and Infectious Diseases (NIAID)
B.J. Medical College, Pune
Weill Cornell Medicine
Johns Hopkins School of Medicine
University of Cape Town
Other Contributor(s)
Abstract
Background: Pregnancy increases the risk of tuberculosis and its complications. A 3-month regimen of weekly isoniazid and rifapentine (3HP) is safe and effective for tuberculosis prevention in adults and children, including those with HIV, but 3HP has not been evaluated in pregnancy. Methods: IMPAACT 2001 was a phase I/II trial evaluating the pharmacokinetics and safety of 3HP among pregnant women with indications for tuberculosis preventative therapy in Haiti, Kenya, Malawi, Thailand, and Zimbabwe (NCT02651259). Isoniazid and rifapentine were provided at standard doses (900 mg/week). Pharmacokinetic sampling was performed with the first (second/third trimester) and twelfth (third trimester/postpartum) doses. Nonlinear mixed-effects models were used to estimate drug population pharmacokinetics. Results: Of 50 participants, 20 had HIV and were taking efavirenz-based antiretroviral therapy. Among women without HIV, clearance of rifapentine was 28% lower during pregnancy than postpartum (1.20 vs 1.53 L/hour, P<.001), with area under the concentration-time curve (AUCSS) of 786 and 673 mg × hour/L, respectively. In pregnant women with HIV, clearance was 30% higher than women without HIV (P<.001), resulting in lower AUCss (522 mg × hour/L); clearance did not change significantly between pregnancy and postpartum. Pregnancy did not impact isoniazid pharmacokinetics. There were no drug-related serious adverse events, treatment discontinuations, or tuberculosis cases in women or infants. Conclusions: 3HP does not require dose adjustment in pregnancy. Rifapentine clearance is higher among women with HIV, but all women achieved exposures of rifapentine and isoniazid associated with successful tuberculosis prevention. The data support proceeding with larger safety-focused studies of 3HP in pregnancy. Clinical Trials Registration: ClinicalTrials.gov, NCT02651259.