Novel vaginal pH buffering spermicide is a new Rx-only option
Thomas MA, Chappell BT, Maximos B, et al. A novel vaginal pH regulator: results from the phase 3 AMPOWER contraception clinical trial. Contracept X. 2020;2:100031.
In an open-label phase 3 study, Thomas and colleagues enrolled 1,384 participants aged 18 to 35 with regular cycles at 112 sites in the United States to assess the contraceptive efficacy, safety, and acceptability of Phexxi vaginal gel (lactic acid, citric acid, and potassium bitartrate) over 7 cycles (6 months). Participants were required to have at least 3 episodes of heterosexual vaginal intercourse per cycle and return throughout the treatment duration for study visits. Fifty-three percent of participants did not complete the study, most frequently due to loss to follow-up (18.1%) and participant withdrawal (12.3%). Most participants were White (69%) and had an average (SD) age of 27.7 (4.5) years.
Efficacy and AE rates
The investigators reported a cumulative pregnancy rate of 13.7% over 7 cycles (6 months). In this study, 45.2% of women experienced 1 AE, and most were noted to be mild (23.9%) to moderate (18.7%). The most reported AE was vulvovaginal burning (20.0%), followed by vulvovaginal pruritus (11.2%), urinary tract infection (5.7%), and vulvovaginal pain (3.8%). Less than 2% of participants discontinued the study due to an AE. Burning and itching decreased with time and with decreased frequency of use. When used twice per day compared with once per day, burning rates decreased from 4.6% to 2.1%, and itching rates decreased from 1.0% to 0.7%. Serious AEs were uncommon, occurring in 1.3% of users; only 1, cystitis, was noted to be “probably” related to the treatment. ●
WHAT THIS EVIDENCE MEANS FOR PRACTICE
Prior to the approval of Phexxi, all currently available vaginal contraceptive gels in the United States contained nonoxynol-9 as the active ingredient, which is a surfactant that is spermicidal by damaging cell membranes. Although Phexxi provides a novel mechanism of action as a spermicide, the contraceptive efficacy is about the same as available spermicides on the market (see TABLE 3).14,22,23 The FDA calculated a 13-cycle PI to include in the label (27.5 pregnancies per 100 woman-years) based on the results of this study; however, no reliable statistical method exists to calculate a true PI from a 7-cycle study. Thus, we recommend that clinicians counsel patients appropriately based on the 6-month rate noted in the study, and that this rate is similar to that with currently available over-the-counter products. This point is important, as Phexxi is available only by prescription, which may impact patient cost and access.
Equally important is Phexxi’s potential for sexually transmitted infection (STI) prevention. In a US-based randomized controlled trial, Phexxi use demonstrated significant risk reduction in gonorrhea and chlamydia infections among participants aged 18 to 45 years.24 That study showed a relative risk reduction of 50% and 78% for chlamydia and gonorrhea, respectively.24 Future research is planned to evaluate this spermicide as a novel STI prevention method. Ultimately, Phexxi may provide an alternative spermicide for users interested in moderately effective contraception and unable to tolerate available nonoxynol-9 formulations. Interested users will have to rely on a prescription, possibly limiting access to this novel spermicide. Further data are required to determine its potential as an STI prevention agent.
