Clinical trial to evaluate pharmacokinetics and pharmacodynamics of medroxyprogesterone acetate after subcutaneous administration of Depo-Provera.
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ABSTRACT: Objective
To evaluate the pharmacokinetics and pharmacodynamics of medroxyprogesterone acetate after a single subcutaneous injection in the abdomen of 150 or 300 mg Depo-Provera and compare results to two injections of Depo-SubQ Provera 104 given 3 months apart.Design
Partially randomized, multicenter, parallel-group study.Setting
Research unit.Patient(s)
Forty-two women of reproductive age with confirmed ovulatory cycle and body mass index of 18-35 kg/m2.Intervention(s)
Women received a single subcutaneous injection of 150 mg (n = 24) or 300 mg (n = 9) of Depo-Provera or two injections of Depo-SubQ Provera 104 (n = 9).Main outcome measure(s)
Suppression of ovulation as measured by progesterone, serum medroxyprogesterone acetate concentrations, and estimated pharmacokinetics parameters.Result(s)
No ovulations were observed during 7 months after a single injection of 150 or 300 mg Depo-Provera. The 150 mg group had a similar Cmax as observed over two injection cycles of Depo-SubQ Provera 104 and a similar 6-month trough concentration as the 3-month trough of Depo-SubQ Provera 104.Conclusion(s)
Our pharmacodynamics and pharmacokinetics data provide proof of concept that Depo-Provera (150 mg) may be an effective contraceptive method when injected subcutaneously every 6 months, with up to a 4-week grace period for reinjections.Clinical trial registration number
NCT02456584.
SUBMITTER: Halpern V
PROVIDER: S-EPMC8051852 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:To evaluate feasibility, acceptability, continuation, and trough serum levels following self-administration of subcutaneous (sc) depot medroxyprogesterone acetate (DMPA).Women 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.Two 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.Sixty-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.Self-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.
| S-EPMC4086940 | biostudies-literature
Project description:Objectives: To identify the lowest dose of Depo-Provera that, when administered off-label subcutaneously, suppressed ovulation and had a pharmacokinetic profile consistent with a 4-month contraceptive effect. Study Design: We conducted a randomized, multicenter, parallel-group study to evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of medroxyprogesterone acetate (MPA) after subcutaneous injection of three different doses of Depo-Provera. We randomized sixty women between 18 and 40 years of age at low risk of pregnancy with confirmed ovulation and body mass index of 18 to 35 kg/m2 to receive a single injection of 45, 75 or 105 mg of Depo-Provera, or a single injection of Depo-subQ provera 104 as a reference drug (15 women per group) and followed them for 7.5 months. We evaluated suppression of ovulation as the primary outcome, and MPA concentrations, pharmacokinetic parameters, safety, and local tolerability as secondary outcomes. Results: Five women ovulated within four months of treatment initiation (three in the 45 mg group and two in the 75 mg group). MPA levels associated with ovulation were in general low, largely ≤ 0.2 ng/mL (the presumed contraceptive threshold). No women in either the 105 mg group or the Depo-subQ provera 104 group ovulated within four months. The PK parameters including Cmax, C119, and AUC0−119 for these 2 groups were similar but not equivalent. Conclusion: A dose of 105 mg of Depo-Provera injected subcutaneously was the lowest tested dose that consistently suppressed ovulation and maintained serum MPA levels consistent with contraceptive effect for at least 4 months. The PK and PD results for the 105 mg dose were similar to Depo-subQ provera 104 over this period.
| S-EPMC8551587 | biostudies-literature
Project description:Objective: The aim of the study was to evaluate the correlation between obesity and the use of depot medroxyprogesterone (DMPA) with regard to weight gain and changes in bleeding pattern.Methods: A retrospective chart review was conducted of women receiving 150 mg DMPA via intramuscular injection at inpatient and outpatient clinics at the University of Mississippi Medical Centre between 1 June 2012 and 31 December 2016. Body mass indices (BMI) were assessed at baseline and at the time of final injection. Data on race, medical history, age at first DMPA injection, number and timing of injections, reported side effects, indication for DMPA use and reason for discontinuation, if applicable, were collected.Results: Of the 240 women included in the study, 3.3% were underweight, 30.8% were normal weight, 23.3% were overweight, 15% were class I obese, 9.6% were class II obese and 17.9% were class III obese; 87.9% of the population were African American. Women gained 2.40 kg (95% confidence interval 1.34-3.45) while they were on DMPA (p < .01), which after adjusting for confounding variables was inversely associated with age at initial injection (β coefficient -0.13; p = .02). Amenorrhoea was the most commonly reported change in bleeding pattern.Conclusion: Women who started DMPA at an earlier age gained the most weight over time, independently of initial BMI. Similar rates of amenorrhoea were found among all BMI categories.
| S-EPMC8569696 | biostudies-literature
Project description:Objective: This study examined the effect of postpartum administration of depo medroxyprogesterone acetate (DMPA) on milk production, time to onset of secretory activation, lactation duration, and infant consumption of mother's own milk (MOM) in mothers of preterm very low-birth-weight (VLBW) infants. Materials and Methods: We conducted a secondary analysis of data from mothers who delivered infants weighing ≤1,500 g and at ≤32 weeks' gestation. The volume of milk produced was measured on days 1-7, 14, and 21 by weighing all expressed milk on an electronic scale. Time to secretory activation was determined through self-report of a feeling of breast fullness. Information on lactation duration and the percent of feeds consisting of MOM consumed by infants was obtained from the medical records. Results: Mothers who received postpartum DMPA were more likely to be African American (72.4% versus 31.4%; p = 0.0006), unemployed (65.5% versus 44.5%; p = 0.027), and Medicaid eligible (89.7% versus 67.2%; p = 0.019). There were no differences in daily milk production between mothers who received DMPA before hospital discharge (n = 29) compared with those who did not (n = 141). When mothers who reached secretory activation before receiving DMPA were removed from analysis, receiving DMPA was associated with a later onset of secretory activation (103.7 versus 88.6 hours; p = 0.028). There were no statistically significant differences between the study groups in lactation duration or infant MOM consumption. Conclusions: DMPA, when administered postpartum to mothers of preterm VLBW infants, delayed secretory activation, but had no detrimental effect on milk production or lactation duration. Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT01892085.
| S-EPMC8817730 | biostudies-literature
Project description: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.
| S-EPMC7384316 | biostudies-literature
Project description:BackgroundSubcutaneous depot medroxyprogesterone acetate is an easy-to-use injectable contraceptive. A trained person can administer it, including women through self-injection. The objective of this systematic review and meta-analysis was to assess the effectiveness and safety of self-injection versus provider-administered subcutaneous depot medroxyprogesterone acetate for improving continuation of contraceptive use.MethodsWe searched for randomized controlled trials on November 1, 2020 in Cochrane Central Register of Controlled Trials, MEDLINE, CINAHL, Embase, Web of Science, Scopus, Open Grey, clinical trials registries, and reference lists of relevant studies. We did not impose any search restrictions. We included randomized trials comparing self- versus provider-administered subcutaneous depot medroxyprogesterone acetate. Two authors independently screened trials, extracted data, and assessed the risk of bias in the included studies. We used risk ratio and 95% confidence intervals for dichotomous outcomes.ResultsWe identified 3 randomized trials (9 reports; 1264 participants). The risk of bias in the included studies was low except for performance bias and detection bias of participant-reported outcomes in unmasked trials. Self-administration, compared to provider-administration, increased continuation of contraceptive use (risk ratio 1.35; 95% confidence intervals 1.10-1.66); moderate-certainty evidence). Self-injection appears to be making more of an impact on continuation for younger women compared to women 25 years and older and on women living in low and middle income compared to high income countries. There was no subgroup difference by the type of care provider (community health worker vs. clinic-based provider).ConclusionsSelf-injection of subcutaneous depot medroxyprogesterone acetate probably improves continuation of contraceptive use. The effects on other outcomes remain uncertain because of the very low certainty of evidence.
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Project description:PurposeRemimazolam is a novel and ultra-short-acting sedative currently developed for intravenous use in procedural sedation, general anesthesia, and ICU sedation. However, intravenous administration is not always appropriate, depending on the patient or setting. This study evaluated intranasal administration as a potential alternative route.MethodsThe study used a randomized, double-blind, 9 period cross-over design to compare the pharmacokinetics, pharmacodynamics, and safety of single intranasal doses of 10, 20, and 40 mg remimazolam (as powder or solution) with intranasal placebo and 4 mg intravenous remimazolam.ResultsIntranasal remimazolam powder had a consistent absolute bioavailability of approximately 50%; Tmax was 10 min; AUC and Cmax were dose-proportional. The higher doses of intranasal solution, however, resulted in decreasing bioavailability and loss of dose-proportionality in AUC and Cmax despite complete drug absorption due to partial swallowing of dose and the resulting first-pass effect. Pharmacodynamics were generally consistent with PK. Peak effects (drowsiness, relaxation, any, memory, response time) were in similar ranges after intranasal (10 to 40 mg) as intravenous (4 mg) dosing and were partially, but not consistently, dose-related. Safety results were generally consistent with other benzodiazepines; however, intranasal remimazolam (but not placebo) caused nasal discomfort/pain, in some cases even severe.ConclusionsIntranasal administration of remimazolam was safe and caused sedative effects. However, the severe pain and discomfort caused by intranasal remimazolam prohibit its use by this route of administration, at least with the currently available intravenous formulation.
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Project description:The Republic of Benin faces high maternal, newborn, and child mortality; low modern contraceptive use; and a critical shortage of health workers. In 2013, the Government of Benin made 3 reproductive health commitments to improve national health indicators, including expanding provision of family planning services at the community level through task sharing. Since 2016, the Advancing Partners & Communities (APC) project has been helping the Benin Ministry of Health (MOH) provide subcutaneous depot medroxyprogesterone acetate (DMPA-SC; brand name Sayana Press) through facility-based health care providers and community health workers known as relais communautaires (RCs). DMPA-SC is an easy-to-administer, discreet injectable contraceptive that provides 3 months of protection from pregnancy. Beginning in May 2017, the government introduced DMPA-SC through a phased approach in 10 health zones, which encompassed 149 health centers and 614 villages. Between June 2017 and June 2018, the MOH and APC trained 278 facility-based providers and 917 RCs to provide DMPA-SC, and nearly 11,000 doses were subsequently administered to 7,997 women at facilities and in communities. This article presents findings from an assessment of community-level and health facility service data collected during the first 13 months of DMPA-SC introduction in Benin. Because of this intervention, nearly 35,000 women received family planning counseling and 7,997 women chose DMPA-SC. At the community level, 3,111 DMPA-SC users were first-time users of modern contraception. The initial success of the DMPA-SC rollout in Benin shows promise for helping the country meet its reproductive health commitments.
| S-EPMC6641808 | biostudies-literature
Project description:ObjectiveTo assess the supply- and demand-side factors influencing continued use of the injectable contraceptive subcutaneous depot medroxyprogesterone acetate (DMPA-SC).MethodsWe conducted a 12-month randomized controlled trial in Malawi to measure DMPA-SC continuation rates. A total of 731 women presenting to clinic-based providers (CBPs) at 6 Ministry of Health clinics or to community health workers (CHWs) in rural communities were randomized to receive DMPA-SC administered by a provider or be trained to self-inject DMPA-SC. Data collectors contacted women after the reinjection window at 3, 6, and 9 months to collect data on discontinuation and women's experiences. Twelve months after enrollment or at early discontinuation, women had their final interview, including pregnancy testing. We compared continuation, pregnancy, and safety by whether DMPA-SC or self-injection training was provided by CHWs versus CBPs. We also conducted an exploratory analysis assessing the association between women's sociodemographic factors and the risk for discontinuation using stratified Cox proportional hazards models.FindingsThe type of provider did not seem to influence continuation, pregnancy, or safety. As reported previously, women in the self-injection group were significantly less likely to discontinue the method compared with women in the provider-administered group (hazard ratio, 0.43; P<.001). The risk for discontinuation was also different among health facility catchment sites (P<.001). No other assessed sociodemographic factors were found to significantly influence the risk for discontinuation.ConclusionsPublic-sector CHWs can safely and effectively provide DMPA-SC and train women to self-inject DMPA-SC in low-resource settings. DMPA-SC continuation did not seem to be influenced by the type of provider, whether CBP or CHW, or women's sociodemographic characteristics.
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