Elsevier

Contraception

Volume 89, Issue 5, May 2014, Pages 341-343
Contraception

Commentary
Subcutaneous DMPA: a better lower dose approach

https://doi.org/10.1016/j.contraception.2013.10.010Get rights and content

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Concern about DMPA's dose and high “frontloading” pattern

Still, throughout its history, DMPA has been dogged by controversy. Most recently, injectables have been implicated as possibly increasing risk of HIV acquisition, though the evidence remains far from persuasive [4]. More tangibly, DMPA at its current 150 mg IM dose has detectable metabolic effects. For example, weight gain is very common. And like pregnancy (though to a lesser degree), it impairs glucose tolerance, enough so that risk of diabetes may be increased for women with borderline

Subcutaneous route a better approach

We can do better for women. Remarkably, while DMPA has historically been administered IM, it turns out that simply providing DMPA subcutaneously (SQ) provides a much better pharmacokinetic profile with substantially lower peak levels, lower overall dose and, apparently, more stable sustained blood levels. Thus, one pharmaceutical company (Pfizer) has developed a modified 104-mg 3-month formulation of DMPA specifically for SQ injection [6]. This formulation provides 30% less drug and reduces

Additional circa 100 mg 3-month SQ versions

Simply applying the current IM DMPA formulation in a 100-mg SQ version for administration through a needle and syringe would seem to be the simplest and most straightforward incremental step toward a widely available lower dose. This approach would follow in the footsteps of Pfizer's already successful development of its 104-mg product designed for Uniject. Actually, even 100 mg of the standard formulation given IM provides excellent efficacy. In the 1980s the World Health Organization

50–75 mg 3-month SQ versions

The evidence in Fig. 3 gives promise for even further potential dose reduction. The 75-mg dose stays on average above 0.2 ng/mL level, which we believe is more than enough to achieve excellent efficacy. One reason we believe that further dose reduction is highly probable is that heretofore approaches to efficacy with DMPA have largely adopted an ultra-conservative approach, aiming for doses high enough to avoid even a hint of ovulation. In the Pfizer study, only 1 woman of 12 on the 75-mg dose

Longer term (e.g., 6 month) SQ versions

Fig. 3 also suggests potential for a longer term SQ injectable, which would greatly expand choice and utility for women. The 150-mg dose curve slopes gently downward and still stays well elevated at 112 days, suggesting that the 150-mg dose could maintain efficacy for a considerably longer time such as 6 months but with overall reduced drug exposure, compared with two current 150-mg IM 3-month injections.

Remarkably, even the current 104-mg SQ formulation promises considerably longer efficacy,

Action needed

A clear advantage with each of these three approaches is that they can be carried out, at least in the first instance with the current IM formulations. Development of 100-mg versions should be the easiest and might involve only replication of dose-finding studies. However, development of the 50–75-mg 3-month and the 6-month approaches call first for dose-finding and biomarker assessment. If these are promising, then they would be followed by clinical trial evaluation to determine the actual

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