Lactic Acid, L-, Citric Acid Monohydrate, and Potassium Bitartrate

PHEXX is indicated for the prevention of pregnancy in females of reproductive potential for use as an on-demand method of contraception. PHEXX is a combination of lactic acid, citric acid, and potassium bitartrate indicated for the prevention of pregnancy in females of reproductive potential for use as an on-demand method of contraception. ( 1 ) Limitations of Use: PHEXX is not effective for the prevention of pregnancy when administered after intercourse. Limitations of Use PHEXX is not effective for the prevention of pregnancy when administered after intercourse [ see Dosage and Administration (2.1) ].

Vaginal gel: 18 mg of lactic acid, 10 mg of citric acid, and 4 mg of potassium bitartrate in each gram (1.8%, 1%, and 0.4%, respectively) of off-white to tan color gel supplied in a pre-filled single-dose (5 grams) vaginal applicator Each pre-filled single-dose vaginal applicator delivers 5 grams of gel containing lactic acid (1.8%), citric acid (1%), and potassium bitartrate (0.4%). ( 3 )

Cystitis and Pyelonephritis: Avoid use in women with a history of recurrent UTI or urinary tract abnormalities ( 5.1 )

5.1 Cystitis and Pyelonephritis Among 2804 subjects who received PHEXX in Studies 1 and 2, 0.36% (n=10) reported adverse reactions of cystitis, pyelonephritis, or other upper urinary tract infection (UTI). Of these, one case of pyelonephritis was considered serious and required hospitalization. Avoid use of PHEXX in females of reproductive potential with a history of recurrent urinary tract infection or urinary tract abnormalities.

The following clinically significant adverse reactions are described elsewhere in the labeling: Cystitis and Pyelonephritis [ see Warnings and Precautions (5.1) ] Most common adverse reactions (≥2%) were vulvovaginal burning sensation, vulvovaginal pruritus, vulvovaginal mycotic infection, urinary tract infection, vulvovaginal discomfort, bacterial vaginosis, vaginal discharge, genital discomfort, dysuria, and vulvovaginal pain. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Evofem at toll-free phone 1-833-EVFMBIO or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of PHEXX (pre-filled applicator with 5-gram dose) has been evaluated in two clinical trials (Study 1 and Study 2) in 2804 subjects (over 19,000 cycles of exposure). The racial/ethnic distribution was 66% White, 27% Black or African American, 2% Asian, 1% American Indian or Alaska Native, 0.3% Native Hawaiian or Pacific Islander, and 5% other; 32% of the study population was Hispanic. Study 1 included a one-year extension phase where 342 U.S. subjects were exposed to PHEXX for 13 cycles. Hypersensitivity Reaction Of the 2804 PHEXX-treated subjects in Studies 1 and 2, one subject reported a suspected drug hypersensitivity. Avoid PHEXX use in females of reproductive potential with suspected hypersensitivity to the ingredients in PHEXX. The most common adverse reactions (≥10%) in the U.S. population in Studies 1 and 2 (n=2480) were: vulvovaginal burning sensation (18.0%) and vulvovaginal pruritus (14.5%). The majority of these adverse reactions were mild and few led to discontinuation. Table 1 summarizes the most common adverse reactions (≥2%) reported by subjects using PHEXX in the U.S. Table 1. Adverse Reactions that Occurred in ≥2% of Subjects Who Used PHEXX to Prevent Pregnancy (Studies 1 and 2 – U.S. population only) Adverse Reaction PHEXX (N=2480) (%) Vulvovaginal Burning Sensation

18.0 Vulvovaginal Pruritus

14.5 Vulvovaginal Mycotic Infection Includes preferred terms (PT) vulvovaginal mycotic infection and vulvovaginal candidiasis.

9.1 Urinary Tract Infection Includes PTs urinary tract infection, streptococcal urinary tract infection, Escherichia urinary tract infection, and urinary tract infection bacterial. Does not include PTs cystitis, kidney infection, and pyelonephritis [ see Warnings and Precautions (5.1) ].

9.0 Vulvovaginal Discomfort

9.0 Bacterial Vaginosis

8.4 Vaginal Discharge

5.5 Genital Discomfort

4.1 Dysuria

3.1 Vulvovaginal Pain

2.1 Among subjects who used PHEXX in Studies 1 and 2, 1.6% discontinued from the clinical trials due to an adverse reaction. The most common adverse reactions leading to study discontinuation were vulvovaginal burning sensation (0.7%); and vulvovaginal pruritus and vulvovaginal discomfort (0.1% each). Adverse Reactions in Male Partners Among male partners of subjects who used PHEXX for contraception in Study 2, 9.8% (131 of 1330) reported symptoms of local discomfort (burning, itching, pain, and "other"). Of these local discomfort symptoms, 74.7% were mild, 21.4% were moderate, and 3.9% were severe. Two subjects discontinued participation in the study due to male partner symptoms.

8.1 Pregnancy Risk Summary There is no use for PHEXX in pregnancy; therefore, discontinue PHEXX during pregnancy. There are no data with the use of PHEXX in pregnant women or animals. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4 percent and 15 to 20 percent, respectively.

8.2 Lactation Risk Summary There are no data on the presence of lactic acid, citric acid, and potassium bitartrate or their metabolites in human milk, the effects on the breastfed infant, or the effects on milk production.

8.4 Pediatric Use The safety and effectiveness of PHEXX have been established in females of reproductive potential. Efficacy is expected to be the same for post-menarchal females under the age of 17 as for users 17 years and older. The use of PHEXX before menarche is not indicated.

In in vitro studies, PHEXX produced a normal vaginal pH range (pH 3.5 – 4.5) in the presence of semen. In clinical studies, post-coital testing demonstrated pH <5 in the majority of subjects, and sperm motility reduction.