Phexxi - Drug Monograph

Introduction

Phexxi (lactic acid, citric acid, and potassium bitartrate) is a non-hormonal, on-demand vaginal gel contraceptive approved by the FDA in 2020. It represents a novel approach to contraception by creating an acidic environment in the vagina that is inhospitable to sperm. Unlike systemic hormonal contraceptives, Phexxi acts locally and is administered immediately before or up to one hour prior to each act of vaginal intercourse.

Mechanism of Action

Phexxi works through a physicochemical mechanism rather than hormonal action. The combination of lactic acid, citric acid, and potassium bitartrate creates and maintains an acidic environment in the vagina (pH ≤ 3.5). This acidic environment is spermicidal, as sperm require a more alkaline environment (pH 7-8) for optimal motility and function. The low pH immobilizes and kills sperm, preventing fertilization without affecting systemic hormone levels.

Indications

Phexxi is indicated for use by females of reproductive potential to prevent pregnancy. It is approved as a non-hormonal contraceptive option for women who prefer or require non-hormonal contraception. It should be noted that Phexxi is less effective than many other contraceptive methods, with a typical use failure rate of approximately 21%.

Dosage and Administration

• Dosage: One pre-filled applicator (5 mL) per act of intercourse
• Administration: Intravaginally immediately before or up to 1 hour prior to each act of vaginal intercourse
• Frequency: Must be administered before every act of vaginal intercourse
• Special populations: No dosage adjustment required for renal or hepatic impairment
• Not recommended for use with other vaginal products or during menstruation

Pharmacokinetics

• Absorption: Minimal systemic absorption; primarily local action in the vaginal tract
• Distribution: Localized to vaginal tissues with negligible systemic distribution
• Metabolism: No hepatic metabolism; components are normal biological acids
• Elimination: Components are eliminated through normal metabolic pathways
• The active ingredients are naturally occurring substances already present in the body

Contraindications

1. Known hypersensitivity to any component of the formulation 2. Recurrent urinary tract infections (UTIs) or history of UTI complications 3. Anatomical anomalies that affect vaginal anatomy or function 4. Use with other vaginal products or medications

Warnings and Precautions

• UTI Risk: Significantly increases risk of urinary tract infections (6% incidence in clinical trials)
• Bacterial vaginosis: May increase risk of bacterial vaginosis
• Vulvovaginal burning: Common side effect that may affect adherence
• Contraceptive efficacy: Less effective than many other contraceptive methods
• STI protection: Does not protect against sexually transmitted infections
• Use in adolescents: Safety and efficacy established for females of reproductive age

Drug Interactions

• Vaginal products: Do not use concurrently with other vaginal products (creams, gels, lubricants)
• Vaginal medications: May alter absorption or efficacy of vaginally administered medications
• Spermicides: Not studied with other spermicidal products
• Condoms: Not recommended for use with latex condoms (may compromise integrity)

Adverse Effects

• Vulvovaginal burning sensation (20%)
• Vulvovaginal itching (12%)
• Yeast infection (8%)
• Urinary tract infection (6%)
• Bacterial vaginosis (6%)
• Vaginal discharge (5%)
• Genital discomfort (4%)
• Dysuria (3%)

• Severe allergic reactions (rare)
• Complicated urinary tract infections
• Pelvic inflammatory disease (theoretical risk)

Monitoring Parameters

1. Contraceptive efficacy: Pregnancy testing if menstrual period is delayed 2. UTI symptoms: Monitor for dysuria, frequency, urgency, or suprapubic pain 3. Vaginal health: Assess for signs of vulvovaginitis, burning, or itching 4. Adherence: Evaluate proper administration technique and consistency of use 5. Sexual health: Regular STI screening as appropriate

Patient Education

• Must be used before every act of vaginal intercourse for maximum efficacy
• Proper administration technique: Insert applicator fully into vagina and depress plunger
• Not a lubricant - additional lubrication may be needed
• Does not protect against sexually transmitted infections
• Seek medical attention for UTI symptoms (burning with urination, frequent urination)
• Store at room temperature (20-25°C)
• Discontinue use and consult healthcare provider if severe irritation occurs
• Consider backup contraception if vomiting or diarrhea occurs shortly after administration
• Effectiveness is time-limited - must be administered within 1 hour before intercourse

References

1. FDA Prescribing Information: Phexxi (lactic acid, citric acid, and potassium bitartrate) vaginal gel. 2020. 2. Thomas MA, Chai SJ, Browne EF, et al. Contraceptive efficacy of a novel acid-buffering bioadhesive vaginal gel. Contraception. 2019;100(5):400-404. 3. Archer DF, Merkatz RB, Bahamondes L, et al. Efficacy of the vaginal pH regulator for the prevention of pregnancy. Obstet Gynecol. 2019;134(5):1040-1050. 4. Creinin MD, Meyn LA, Borgatta L, et al. Multicenter comparison of the contraceptive ring and patch. Obstet Gynecol. 2008;111(2 Pt 1):267-277. 5. ClinicalTrials.gov. Phase 3 study of Amphora for the prevention of pregnancy. NCT03243344.