Meet Phexxi – A New Non-Hormonal Contraceptive Gel

Image from https://hcp-phexxi.com

About the Product

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.1

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.1

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.2

What Patients Can Expect

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.1

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.2

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.2

Offering This New Option to Patients

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.2

Spermicide is also available as a vaginal gel, but it is only about 72% effective with typical use.3 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.4 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.5

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 2020.6

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

REFERENCES

  1. 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. Contraception: X.2020; vol. 2 100031.
  2. Phexxi. Prescribing information. Evofem Biosciences; 2020. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/208352s000lbl.pdf. Accessed June 17, 2020.
  3. HHS. Spermicide. https://www.hhs.gov/opa/pregnancy-prevention/birth-control-methods/spermicide/index.html. Accessed June 17, 2020.
  4. FDA. Code of Federal Regulations Title 21; April 1, 2019. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm?fr=201.325. Accessed August 3, 2020.
  5. 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. Accessed August 30, 2020.
  6. 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. Accessed August 3, 2020.
  7. 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. Accessed August 3, 2020.

About the Author

This article was co-written by Whitney Russell, a student pharmacist at University of Kentucky College of Pharmacy.

This article was originally published in Pharmacy Times.

FDA Updates on Birth Control

There have been some notable changes with birth control products, including three new product approvals and one product exiting the market.

1. New yearly birth control vaginal ring approved. This birth control ring is very different from the existing vaginal ring product since it works for 1 year. It is a combined hormonal product and contains ethinyl estradiol and a new progestin — segesterone acetate. The ring is placed in the vagina for three weeks followed by one week out of the vagina, at which time women may experience a period (a withdrawal bleed). This schedule is repeated every four weeks for one year. The brand name is Annovera. One advantage of this product is that it does not require refrigeration. It is expected to be available in 2019. For more info, FDA News Release and Manufacturer Press Release.

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2.  First direct-to-consumer birth control digital app approved. This is the first app approved by the FDA as a safe and effective method of contraception.  It is indicated for use by adults aged 18 years and older. The app must be used with a thermometer — a two decimal basal thermometer, which is not the same as a normal fever thermometer.

Users will measure their temperature first thing in the morning before they get up and out of bed (at least five mornings a week) and enter it into the app.  For the algorithm to calculate daily fertility, users will also need to add their period data each month. The Natural Cycles algorithm analyses the information entered into the app to detect ovulation, thereby identifying green days, when no protection is needed, or red days, when you should use condoms or abstain from sex to prevent a pregnancy. For more info, FDA News Release and Company Website.

Natural Cycles Birth Control App

3. Another generic levonorgestrel emergency contraceptive pill approved. New generic emergency contraception (EC) pill approved. Preventeza is the brand name and it is made by the makers of Vagisil. This is another Levonorgestrel 1.5 mg single-pill EC product that may be sold without a prescription to consumers of all ages — women and men. It is available online only from the manufacturer’s website.

Preventeza Emergency Contraception

4. Essure to be discontinued. Essure is a permanent birth control method that doesn’t requires surgery and is placed in an office-based procedure. In this procedure, a soft, flexible insert is delivered through the vagina and uterus and permanently placed in each fallopian tube. No incision is required to deliver or place the inserts and general anesthesia is not required. Over time, a natural barrier forms around the inserts and prevents sperm from reaching the eggs by occluding the fallopian tubes. During this time, the patient must continue using another form of birth control to prevent pregnancy until the confirmation test at 3 months post-procedure.

The manufacturer is discontinuing production and it will no longer be available at the end of 2018.  This may be due to complaints from users due to adverse effects, restrictions by the FDA in April of this year, and/or low utilization. For more info, FDA Press Announcement.

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This has been a busy time for birth control product changes. We always welcome new birth control options to fit patient needs, given they are safe and effective.