Dataset Information

Pharmacokinetics and Pharmacodynamics of Depot Medroxyprogesterone Acetate in African Women Receiving Treatment for Human Immunodeficiency Virus and Tuberculosis: Potential Concern for Standard Dosing Frequency.

ABSTRACT: BACKGROUND:Effective contraception is critical to young women with HIV-associated tuberculosis (TB), as unintended pregnancy is associated with increased perinatal morbidity and mortality. The effects of co-administration of efavirenz and rifampicin on the pharmacokinetics of depot medroxyprogesterone acetate (DMPA) are unknown. We hypothesized that clearance of medroxyprogesterone acetate (MPA) would increase when given with rifampicin and efavirenz, thus increasing risk of ovulation. METHODS:This pharmacokinetics (PK) study assessed DMPA among HIV/TB coinfected women on an efavirenz-based antiretroviral treatment and rifampicin-based TB treatment. Plasma MPA concentrations and progesterone were measured predose (MPA only) and 2, 4, 6, 8, 10, and 12 weeks after a single DMPA 150 mg intramuscular injection. The primary outcome measure, MPA concentration (<0.1 ng/mL) at week 12, was assessed using exact 95% Clopper-Pearson confidence intervals. MPA PK parameters were calculated using noncompartmental analysis. RESULTS:Among 42 PK-evaluable women from 5 African countries, median age was 32 years and median CD4 was 414 cells/mm3. Five women (11.9%; 95% CI, 4.0-25.6%) had MPA <0.1 ng/mL at week 12; of these, one had MPA <0.1 ng/mL at week 10. The median clearance of MPA was 19 681 L/week compared with 12 118 L/week for historical controls. There were no adverse events related to DMPA, and progesterone concentrations were <1 ng/mL for all women for the study duration. CONCLUSIONS:DMPA, when given with rifampicin and efavirenz, was safe. MPA clearance was higher than in women with HIV not on ART, leading to subtherapeutic concentrations of MPA in 12% of women, suggesting that more frequent dosing might be needed. CLINICAL TRIALS REGISTRATION:NCT02412436.

SUBMITTER: Mngqibisa R

PROVIDER: S-EPMC7384316 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Pharmacokinetics and Pharmacodynamics of Depot Medroxyprogesterone Acetate in African Women Receiving Treatment for Human Immunodeficiency Virus and Tuberculosis: Potential Concern for Standard Dosing Frequency.

Mngqibisa Rosie R Kendall Michelle A MA Dooley Kelly K Wu Xingye Shirley XS Firnhaber Cynthia C Mcilleron Helen H Robinson Jennifer J Cramer Yoninah Y Rosenkranz Susan L SL Roa Jhoanna J Coughlin Kristine K Mawlana Sajeeda S Badal-Faesen Sharlaa S Schnabel David D Omoz-Oarhe Ayotunde A Samaneka Wadzanai W Godfrey Catherine C Cohn Susan E SE

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20200701 3

<h4>Background</h4>Effective contraception is critical to young women with HIV-associated tuberculosis (TB), as unintended pregnancy is associated with increased perinatal morbidity and mortality. The effects of co-administration of efavirenz and rifampicin on the pharmacokinetics of depot medroxyprogesterone acetate (DMPA) are unknown. We hypothesized that clearance of medroxyprogesterone acetate (MPA) would increase when given with rifampicin and efavirenz, thus increasing risk of ovulation.<h ...[more]

PMID: 31504342

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Project description:ObjectiveInvestigate the association between use of depot medroxyprogesterone acetate (DMPA) (an injectable progestin-only contraceptive) and leiomyoma development.MethodsWe conducted a cohort study in the Detroit, Michigan, area that involved four clinic visits at 20-month intervals over 5 years (2010-2018) and used a standardized ultrasonography protocol to prospectively measure leiomyomas 0.5 cm or more in diameter. Participants were 1,693 self-identified Black women aged 23-35 years with no prior leiomyoma diagnosis and no hysterectomy. For this substudy, years since last use of DMPA was ascertained from questionnaire data at every visit. Leiomyoma incidence was defined as the first visit with an observed leiomyoma among women who were leiomyoma-free at enrollment. Depot medroxyprogesterone acetate associations were examined with Cox models. Leiomyoma growth was calculated as the change in log-volume for leiomyomas matched at successive visits and was modeled using linear mixed models accounting for clustered data. Leiomyoma loss, defined as a reduction in leiomyoma number in successive visits, was modeled using Poisson regression. All models used time-varying exposure and covariates.ResultsOf participants with at least one follow-up visit (N=1,610), 42.9% had ever used DMPA. Participants exposed to DMPA within the previous 2 years experienced reduced leiomyoma development during the subsequent observation interval compared with never users, including lower leiomyoma incidence (5.2% vs 10.7%), adjusted hazard ratio 0.6 (95% CI 0.4-1.0), 42.0% lower leiomyoma growth (95% CI -51.4 to -30.7) and 60% greater leiomyoma loss (adjusted risk ratio 1.6, 95% CI 1.1-2.2). Excess leiomyoma loss was also seen for those who used DMPA 2-4 years before the visit compared with never users, 2.1-fold increase (95% CI 1.4-3.1).ConclusionRecent use of DMPA was associated with reduced leiomyoma development and increased leiomyoma loss. Such changes in early leiomyoma development in young women could delay symptom onset and reduce the need for invasive treatment.

Project description:ObjectiveTo examine the rate of ovulatory disruption when intramuscular depot medroxyprogesterone acetate (DMPA) is administered across graded stages of dominant follicle development.Study designWe assigned enrolled participants to one of three preassigned dominant follicle size groups: 12-14?mm, 15-17?mm and?? 18?mm. We followed dominant follicles via serial transvaginal ultrasound (TVUS) until the follicles reached their assigned size, at which time we administered DMPA. For 5 consecutive days thereafter, we followed the follicles via TVUS to observe follicle rupture and obtained serum luteinizing hormone (LH), estradiol, and progesterone concentrations. In the following 2 weeks, we collected serum progesterone concentrations twice weekly to detect possible ovulatory delay or dysfunction. We also collected serum medroxyprogesterone acetate (MPA) concentrations at 1 and 24?h after DMPA administration to examine against ovulatory outcomes.ResultsTwenty-six of 29 enrolled women completed the study. DMPA suppressed ovulation in 17/26 (65%) and caused ovulatory dysfunction in 1/26 (4%) participants. Larger follicles were more likely to rupture despite DMPA (12-14?mm: 0/10 (0%); 15-17?mm: 3/10 (30%); ? 18?mm: 6/6 (100%); p?<?.01). Pre-DMPA LH concentrations ranged from 13.8 to 93.7?IU/L (mean 49.0?IU/L) in cases of follicle rupture. We observed no cases of follicle rupture when DMPA was administered through cycle day 12. All 24-h MPA concentrations exceeded those needed for ovulation suppression.ConclusionDMPA suppressed and additionally disrupted ovulation in 65% and 4% of observed cycles, respectively. DMPA may provide effective emergency contraception as well as ongoing contraception if administered prior to an expected ovulation and specifically before the LH surge.ImplicationsDMPA may be an alternative form of emergency contraception that can also self-bridge to ongoing contraception. As ovulation was not observed among any follicles when DMPA was given through cycle day 12, women who initiate DMPA up through cycle day 12 may not require backup contraception.

Project description:ObjectivesTo evaluate feasibility, acceptability, continuation, and trough serum levels following self-administration of subcutaneous (sc) depot medroxyprogesterone acetate (DMPA).Study designWomen presenting to a family planning clinic to initiate, restart or continue DMPA were offered study entry. Participants were randomized in a 2:1 ratio to self- or clinician administered sc DMPA 104 mg. Those randomized to self-administration were taught to self-inject and were supervised in performing the initial injection; they received printed instructions and a supply of contraceptive injections for home use. Participants randomized to clinician administration received usual care. Continued DMPA use was assessed by self-report and trough medroxyprogesterone acetate levels at 6 and 12 months.ResultsTwo hundred fifty women were invited to participate, and 137 (55%) enrolled. Of these, 91 were allocated to self-administration, and 90/91 were able to correctly self-administer sc DMPA. Eighty-seven percent completed follow-up. DMPA use at 1 year was 71% for the self-administration group and 63% for the clinic group (p=0.47). Uninterrupted DMPA use was 47% and 48% for the self and clinic administration groups at 1 year (p=0.70), respectively. Serum analyses confirmed similar mean DMPA levels in both groups and therapeutic trough levels in all participants.ConclusionsSixty-three percent of women approached were interested in trying self-administration of DMPA, even in the context of a randomized trial, and nearly all eligible for enrollment were successful at doing so. Self-administration and clinic administration resulted in similar continuation rates and similar DMPA serum levels. Self-administration of sc DMPA is feasible and may be an attractive alternative for many women.ImplicationsSelf-administration of sc DMPA is a feasible and attractive option for many women. Benefits include increased control over contraceptive measures and less time spent on contracepting behaviors. Globally, self-administration has the potential to revolutionize contraceptive uptake by increasing the number of women with access to DMPA.

Dataset Information

Pharmacokinetics and Pharmacodynamics of Depot Medroxyprogesterone Acetate in African Women Receiving Treatment for Human Immunodeficiency Virus and Tuberculosis: Potential Concern for Standard Dosing Frequency.

Publications

Pharmacokinetics and Pharmacodynamics of Depot Medroxyprogesterone Acetate in African Women Receiving Treatment for Human Immunodeficiency Virus and Tuberculosis: Potential Concern for Standard Dosing Frequency.

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