Sallie Rafie, PharmD and Whitney Russell, PharmD student

Lactic acid, citric acid, and potassium bitartrate (Phexxi, Evofem Biosciences) is a prescription combination, non-hormonal contraceptive gel approved by the FDA in May 2020. The vaginal gel was found to be 86.3% effective with typical use when inserted up to 1 hour before vaginal intercourse.



The gel acts as a contraceptive by maintaining the vaginal pH within its normal range of 3.5 to 4.5, an environment too acidic for sperm to survive. This pH regulating mechanism decreases sperm viability and supports bacteria integral to the vaginal microbiome.



The gel is supplied in a package of twelve, single dose (5 grams), pre-filled applicators with an attachable plunger. The applicator should be inserted into the vagina immediately before or up to 1 hour before vaginal intercourse, with a new dose needing to be administered prior to each act of intercourse.



The most common adverse events (AEs) were vulvovaginal burning (20%) and vulvovaginal itching (11.2%). Of local AEs, 23.9% were mild, 18.7% were moderate, and 2.3% were severe. Rates of these reactions mostly decreased over time.



Women with a history of recurrent urinary tract infections or urinary tract abnormalities should not use the gel due to the 0.36% incidence of cystitis or pyelonephritis in clinical trials.



Male partners of women using the gel might also experience local AEs such as burning, itching, and pain. However, the local AEs experienced by male partners were generally mild (74.7%), while 21.4% were moderate and 3.9% were severe.



The contraceptive gel is an option for women who are seeking a non-hormonal or on-demand method of birth control. Women preferring to use multiple methods of contraception can combine the gel with diaphragms and latex, polyurethane, and polyisoprene condoms. However, it should not be used with vaginal rings.



Spermicide is also available as a vaginal gel, but it is only about 72% effective with typical use.

 Like the non-hormonal contraceptive gel, it can be used on-demand. Nonoxynol-9, the active ingredient in most spermicides, can cause vaginal irritation and increase the risk of HIV transmission.

 In a clinical trial comparing nonoxynol-9 to the , incidences of vulvovaginal itching, burning, and irritation were similar, with the non-hormonal contraceptive gel having a slightly higher incidence of vulvovaginal burning.



The contraceptive gel’s novel pH modulating mechanism is currently being studied for prevention of gonorrhea and chlamydia in the phase 2B clinical trial AMPREVENCE. Preliminary results from the 4-month study period showed a 50% relative risk reduction of chlamydia and a 78% relative risk reduction of gonorrhea. The clinical trial will move on to phase 3 later in 2020.



Although the gel will be available as a prescription only treatment in September 2020, patients may face barriers to accessing the gel during COVID-19. Evofem Biosciences plans to launch a telemedicine program to support patient and provider access to the contraceptive gel.

 Additionally, barriers to contraception access could be further mitigated by enabling pharmacists to prescribe birth control.



Thomas MA, Chappel BT, Maximos B, Culwell KR, Dart C, Howard B. A novel vaginal pH regulator: results from the phase 3 AMPOWER contraception clinical trial. 

Phexxi. Prescribing information. Evofem Biosciences; 2020. 

https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/208352s000lbl.pdf

https://www.hhs.gov/opa/pregnancy-prevention/birth-control-methods/spermicide/index.html

FDA. Code of Federal Regulations Title 21; April 1, 2019. 

https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm?fr=201.325

Study of Contraceptive Efficacy & Safety of Phexxi™ (Previously Known as Amphora) Gel Compared to Conceptrol Vaginal Gel; March 11, 2020. 

https://clinicaltrials.gov/ct2/show/results/NCT01306331

Evofem Biosciences Reports Positive Top-Line Results from Phase 2b Study of Amphora® for Prevention of Chlamydia and Gonorrhea in Women. Evofem Biosciences; December 2, 2020. 

https://evofem.investorroom.com/2019-12-02-Evofem-Biosciences-Reports-Positive-Top-Line-Results-from-Phase-2b-Study-of-Amphora-R-for-Prevention-of-Chlamydia-and-Gonorrhea-in-Women

U.S. FDA Approves Evofem Biosciences' Phexxi™ (lactic acid, citric acid and potassium bitartrate), the First and Only Non-Hormonal Prescription Gel for the Prevention of Pregnancy. Evofem Biosciences; May 22, 2020. 

https://evofem.investorroom.com/2020-05-22-U-S-FDA-Approves-Evofem-Biosciences-Phexxi-TM-lactic-acid-citric-acid-and-potassium-bitartrate-the-First-and-Only-Non-Hormonal-Prescription-Gel-for-the-Prevention-of-Pregnancy

Articles

Lactic acid, citric acid, and potassium bitartrate is a prescription combination, non-hormonal contraceptive gel found to be 86.3% effective with typical use.

Sallie Rafie, PharmD and Whitney Russell, PharmD student

Articles

New Non-Hormonal Contraceptive Gel Found to Be Effective