Elsevier

Contraception

Volume 70, Issue 4, October 2004, Pages 269-275
Contraception

Original research article
Contraceptive efficacy and safety of DMPA-SC

https://doi.org/10.1016/j.contraception.2004.06.011Get rights and content

Abstract

DMPA-SC 104 mg/0.65 mL is a new, low-dose subcutaneous (SC) formulation of Depo-Provera® contraceptive injection (150 mg/mL medroxyprogesterone acetate injectable suspension) that provides efficacy, safety and immediacy of onset equivalent to Depo-Provera intramuscular (IM) injection. Two large, open-label, Phase 3 studies assessed the 1-year contraceptive efficacy, safety and patient satisfaction with DMPA-SC administered every 3 months (12–13 weeks). Zero pregnancies were reported in both studies, which included a total of 16,023 woman-cycles of exposure to DMPA-SC and substantial numbers of overweight or obese women. DMPA-SC was well-tolerated and adverse events were similar to those reported previously with Depo-Provera IM. Thus, DMPA-SC offers women a new, highly effective and convenient long-acting contraceptive option.

Introduction

Depo-Provera® contraceptive injection (150 mg/mL intramuscular [IM] depot medroxyprogesterone acetate [DMPA] injectable suspension) is a highly effective, 3-month progestin-only contraceptive option that has been in use globally for decades [1]. Approved by the US Food and Drug Administration as a contraceptive in 1992, Depo-Provera has become an increasingly popular hormonal contraceptive option among US women. Use of this convenient, private, long-acting method is associated with immediate and highly effective contraception. In fact, the decline in unintended pregnancy rates among US adolescents during this time is due in part to increased use of Depo-Provera [2], [3], [4], [5]. The minimal user participation required for 3-month injectable Depo-Provera IM results in a “typical use” annual failure rate of 0.3%—more effective than surgical sterilization (0.5%) [6]. In contrast, with as many as 50% of oral contraceptive (OC) users missing at least 1 pill per cycle [7], [8], the “typical use” annual failure rate for OCs can be as high as 8% [6].

With hormonal contraception, the goal is to provide high contraceptive efficacy while using the lowest possible steroidal dose. This trend has resulted in progressive lowering of the standard content of OCs since they became available 4 decades ago. This report details a new, low-dose formulation of DMPA that provides equivalent efficacy and safety to the original formulation while allowing administration by subcutaneous (SC) rather than IM injection. DMPA-SC is a pharmacologically unique, 104 mg DMPA/0.65 mL formulation (16% weight/volume) developed to optimize delivery of DMPA by SC injection [9]. The slower rate of absorption observed with DMPA-SC relative to the IM formulation allows for a lower peak serum medroxyprogesterone (MPA) concentration and a long duration of effect; thus, serum MPA levels are maintained above the required minimum concentration for ovulation suppression over a targeted period of 3 months with a 30% lower SC dose [9].

This article presents the results of two large, pivotal Phase 3 contraceptive trials of DMPA-SC. One of these multinational trials was conducted in North and South America; the other in Europe and Asia. The objectives of these studies were to assess the 1-year contraceptive efficacy, safety and patient satisfaction of the new DMPA-SC (104 mg/0.65 mL) injected SC once every 3 months.

Section snippets

Subjects

Women aged 18 through 49 years who were sexually active and desired long-acting contraception with DMPA-SC, including those who used oral, intrauterine or barrier methods of contraception prior to study initiation, were recruited. Eligible participants had discontinued OC use for at least 2 months prior to enrollment. Inclusion criteria also encompassed women menstruating regularly (with a cycle length of 25–35 days) during the 3 months prior to enrollment, who were willing to rely on the

Subject disposition and demographic characteristics

Of the 722 women in the ITT population of the Americas trial, 489 (67.7%) completed the study. Reasons for discontinuation included AEs (98 women), withdrawal of consent (78 women), loss to follow-up (49 women) and protocol violation (8 women). In the European/Asian trial, there were 1065 women in the ITT population, of whom 856 (80.4%) completed the study. Reasons for discontinuation of this study included AEs (56 women), withdrawal of consent (116 women), loss to follow-up (32 women) and

Discussion

These two large, multinational Phase 3 contraceptive trials have shown that DMPA-SC, injected SC once every 3 months, is a highly effective and well-tolerated method of contraception. The absence of any pregnancies during a combined total of 18,681 woman-cycles of exposure (of which 16,023 excluded months during which barrier contraception was used at least sometimes or no intercourse occurred) in a diverse population of women demonstrates the rapid and sustained efficacy of DMPA-SC.

The

Acknowledgements

The following are acknowledged for their statistical expertise: Cynthia Greenwald, MS, Statistician, Clinical Biostatistics, Pfizer Global Research and Development, Kalamazoo, MI, USA; Lana Turner, MS, Statistician, Clinical Biostatistics, Pfizer Global Research and Development, Kalamazoo, MI, USA and Carol Reid, PhD, Statistician, Clinical Biostatistics, Pfizer Global Research and Development, Sandwich, UK. The following are acknowledged as co-investigators: Jerzy Jakowicki, MD, PhD, II

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    Current affiliation: Hoffmann-La Roche Inc., Nutley, NJ, USA.

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