Citric Acid, Lactic Acid, And Potassium Bitartrate

Introduction Overview

Generic Name

citric acid, lactic acid, and potassium bitartrate

Brand Name

Phexxi

Dosage Form

Vaginal gel, supplied as a prefilled single-dose applicator

Drug Class

Miscellaneous vaginal agents

Pharmacokinetics

Phexxi is a locally acting, non-hormonal contraceptive applied vaginally as a gel formulation containing citric acid (1% w/w), lactic acid (1.8% w/w), and potassium bitartrate (0.4% w/w) in a 5 gram dose delivered via a single-use prefilled applicator. Given its topical vaginal administration, systemic absorption of the active ingredients is minimal to negligible, aligning with its mechanism of action localized to the vaginal environment.

Absorption:
The gel formulation is designed for vaginal administration, optimizing local retention and activity in the vaginal mucosa. Absorption through the vaginal mucosa into systemic circulation is considered minimal due to the physiochemical properties of the acids and potassium bitartrate and their hydrophilic nature. There is no significant systemic bioavailability documented, reducing systemic exposure and associated systemic adverse effects.

Distribution:
Distribution data is limited due to minimal systemic absorption. The active agents primarily act locally within the vaginal canal, modifying vaginal pH and sperm motility. The compounds do not undergo notable distribution into peripheral tissues or systemic compartments.

Metabolism:
Due to limited absorption, systemic metabolic pathways are not significantly involved. The vaginal mucosa and local enzymes may metabolize small quantities of citric and lactic acids through normal physiological pathways; however, this is not a major contributor to the drug's pharmacokinetics. Potassium bitartrate is a potassium salt and is unlikely to undergo metabolism.

Elimination:
Given the topical, local action and minimal systemic absorption, elimination pathways are predominantly via vaginal clearance and natural vaginal secretions. Any small absorbed fractions would potentially be eliminated renally; nonetheless, significant systemic elimination does not occur. Clinical data do not report pharmacokinetic parameters such as half-life, volume of distribution, or systemic clearance for Phexxi, emphasizing its local mode of action without systemic pharmacokinetic profiling.

Dosage Forms

Available Dosage Forms:
Phexxi is supplied as a vaginal gel contained in a prefilled, single-use vaginal applicator. Each applicator contains 5 grams of gel with active ingredients comprising lactic acid USP (1.8% w/w), citric acid USP (1% w/w), and potassium bitartrate USP (0.4% w/w). The gel also contains inactive ingredients such as glycerin, alginic acid, xanthan gum, sodium hydroxide, benzoic acid, and purified water to provide appropriate viscosity and stability.

Dosages for Adults and Adolescents:
The recommended dose is one full prefilled applicator (5 grams of gel) inserted vaginally no more than 1 hour before each act of vaginal intercourse. If more than one act of vaginal intercourse occurs within an hour, a new dose must be applied before the subsequent event. This regimen applies to sexually active women of reproductive potential seeking on-demand contraception.

Specific Patient Populations:
Phexxi can be used safely during any time of the menstrual cycle. Patients who have recently given birth, had an abortion or miscarriage may use Phexxi as soon as it is considered safe by their healthcare provider. The product should not be used during pregnancy. Its safety during breastfeeding is unclear; consultation with a healthcare provider is advised. Patients with a history of frequent urinary tract infections or bladder infections are generally advised not to use Phexxi. There are no specific dose adjustments required for elderly populations since it is intended for women of reproductive age. Phexxi should not be combined with vaginal rings due to potential interactions or reduced efficacy.

Storage:
The gel is stable when stored in its original sealed foil pouch at room temperature, protected from moisture and heat. The gel must be used immediately after opening the pouch.

Summary of available application:
- Vaginal gel, 5 gram prefilled single-use applicator
- Active ingredients per dose: Lactic acid (1.8% w/w), Citric acid (1% w/w), Potassium bitartrate (0.4% w/w)
- One dose prior to intercourse (within 1 hour)
- Additional doses required if intercourse occurs more than once within an hour

Mechanism Of Action

Phexxi acts as a non-hormonal contraceptive through a unique multi-component mechanism that primarily involves modulation of the vaginal pH environment. The combination of lactic acid, citric acid, and potassium bitartrate works synergistically to maintain and stabilize a low vaginal pH typically unfavorable for sperm viability and motility.

The primary molecular action arises from the acidic composition delivered by lactic and citric acids, which acidify the vaginal milieu to a pH that inhibits sperm motility and function. Sperm exposed to this acidic environment exhibit impaired motility and reduced capacity to fertilize an ovum. Potassium bitartrate contributes to maintaining the buffering capacity and osmolarity of the vaginal gel, further supporting the acidic pH stability.

At the cellular level, the reduction in vaginal pH causes destabilization of sperm cell membranes and impairs the enzyme activities necessary for sperm motility, especially flagellar motility crucial for progression through the cervical mucus and toward the fallopian tubes. This acidic environment mimics the natural protective acidity of a healthy vaginal ecosystem, which acts as an innate defense against sperm intrusion.

Clinically, Phexxi’s contraceptive efficacy arises from this rapid pH modulation applied proximal to the time of intercourse, blocking sperm migration and survival. Unlike hormonal contraceptives that interrupt ovulation or implantation, Phexxi’s mechanism is immediate and on-demand, with contraceptive effect only when the gel is administered prior to intercourse.

Comparatively, Phexxi offers a hormone-free alternative to spermicides and barrier methods. Unlike nonoxynol-9, a common spermicide that disrupts sperm membranes via detergent-like effects, Phexxi relies on physiologic pH adjustment, potentially conferring a lower irritation profile and reduced risk of mucosal damage and infection.

Research evidence including clinical trials demonstrated Phexxi’s ability to reduce sperm motility and achieve contraception on demand, without systemic hormonal influences or prolonged use requirements. The intact vaginal mucosa and microbiota are preserved, and the gel can be used in combination with other contraceptive methods, offering flexible contraceptive options.

Pharmacological Actions

Lowers vaginal pH to inhibit sperm motility and viability.
Acts as a non-hormonal, topical contraceptive agent.
Maintains acidic vaginal environment mimicking natural vaginal defense mechanisms.
Reduces sperm membrane stability and enzyme function critical for motility.
Provides on-demand contraception without systemic absorption or hormonal interference.
Buffering action of potassium bitartrate stabilizes acidic pH.
Does not interfere with endogenous vaginal flora or mucosal integrity significantly.
Contraceptive effect limited to presence in vaginal lumen during intercourse.
Compatible with other hormonal or barrier contraceptive methods (except vaginal rings).
Delivers rapid contraceptive effects when applied within 1 hour before sex.
Avoids systemic side effects associated with hormonal contraceptives.
Minimal systemic exposure due to topical application and gel retention.
May reduce risk of certain infections by preserving acidic vaginal environment.
Does not prevent sexually transmitted infections.
Acts locally without systemic metabolism or elimination.

Therapeutic Or Clinical Uses

On-demand contraception to prevent pregnancy in women of reproductive potential.
Non-hormonal contraceptive alternative for patients avoiding hormonal methods.
Suitable for use at any point in the menstrual cycle.
Can be used in combination with other contraceptive methods including condoms, diaphragms, hormonal contraception, or implants.
Contraceptive option post-childbirth, miscarriage, or abortion when clinician deems safe.
Provides contraception without systemic hormonal side effects such as mood changes or thrombosis risk.
An option for women with contraindications to estrogen or progestin.
For women seeking contraception without daily adherence or long-term methods.
Useful for patients sensitive to spermicides like nonoxynol-9 due to lower mucosal irritation.
Offered as a vaginal gel dosage form for ease of self-administration.
Can be used intermittently, only prior to sexual activity.
Does not interfere with breastfeeding hormonal status, but consult with provider for safety.
Facilitates rapid onset of contraceptive action within one hour of application.
May be preferred for those wishing to avoid systemic hormonal exposure.
Does not protect against sexually transmitted infections, so should be combined with barrier methods if STI protection desired.

Side Or Adverse Effects

Vaginal burning sensation shortly after application.
Vaginal itching or discomfort at the application site.
Increased vaginal discharge or abnormal vaginal secretions.
Vaginal irritation including redness or soreness.
Occurrence of bacterial vaginosis or fungal infections in the vagina.
Possible bladder infection (cystitis) presenting with dysuria or urinary frequency.
Rare hypersensitivity reactions including hives, swelling, or difficulty breathing.
Flank, side or lower back pain suggestive of kidney infection.
Local irritation exacerbated by concurrent vaginal infections or use with incompatible vaginal devices like rings.
Discontinuation recommended if severe vaginal irritation or allergic reaction occurs.
Possibility of incomplete contraception if the gel is not used exactly per instructions.
Potential transient irritation that resolves with continued use in some patients.
No evidence of systemic adverse effects due to minimal absorption.
Low incidence of serious adverse reactions reported in clinical trials.
Consult healthcare provider if symptoms of urinary tract infection develop.

Precautions

Do not use Phexxi if already pregnant.
Avoid use if history of frequent bladder or urinary tract infections.
Inform healthcare provider of any allergy to citric acid, lactic acid, potassium bitartrate, glycerin, xanthan gum, alginic acid, sodium hydroxide, or benzoic acid.
Consult doctor if recently gave birth, had miscarriage or abortion before starting use.
Phexxi does not protect against HIV or other sexually transmitted infections; dual protection strategy recommended.
Discuss breastfeeding status and risks with provider before use.
Use with caution in patients prone to vaginal infections or irritation.
Avoid combined use with vaginal rings due to potential incompatibility.
Report any signs of allergic reaction or urinary tract infections promptly.
Do not use as a post-coital contraceptive; must be applied prior to intercourse.
Ensure proper timing and dosing to maximize contraceptive efficacy.
Do not share applicators or medication to prevent infection or cross-contamination.
Store according to instructions to maintain gel integrity and effectiveness.
Pregnancy must be ruled out before initiating therapy.
Continue regular gynecological follow-up while using Phexxi.

Warnings

Strictly follow directions on the label and insert gel within 1 hour prior to vaginal intercourse.
Phexxi is not effective if used after intercourse.
May cause bladder or kidney infection; seek immediate care if urinary symptoms develop.
Discontinue use if severe vaginal irritation or allergic reaction occurs.
Use of Phexxi does not prevent sexually transmitted infections, including HIV.
Avoid use with vaginal rings to prevent reduced contraceptive efficacy.
Do not use if allergic to any of the components including active acids or excipients.
Pregnant women should not use Phexxi due to risk of adverse effects.
Safety during breastfeeding is uncertain; consult healthcare provider.
Keep out of reach of children; not intended for use by males or women not of reproductive potential.
Risk of pregnancy increases if dosing instructions are not followed precisely.
Inform healthcare provider if experiencing recurrent urinary tract infections while using Phexxi.
Gel integrity can be compromised if applicator pouch is damaged or opened prematurely.
Store at room temperature away from moisture and heat to maintain product efficacy.

Contraindication

Known hypersensitivity or allergy to citric acid, lactic acid, or potassium bitartrate.
Pregnancy: Phexxi is contraindicated in women who are pregnant.
History of frequent or recurrent urinary tract infections or bladder infections.
Concurrent use with vaginal rings.
Presence of severe vaginal irritation or mucosal lesions.
Known hypersensitivity to inactive ingredients including glycerin, alginic acid, xanthan gum, sodium hydroxide, or benzoic acid.
Women without reproductive potential as the contraceptive effect is irrelevant.
Active vaginal infections untreated at the time of intended use until appropriate therapy is completed.
Known hypersensitivity to related topical vaginal agents or contraceptive gels.
Patients unwilling or unable to comply with product usage instructions.
Presence of vaginal bleeding of unknown etiology.
Women with bladder dysfunction affecting urination.
Severe mucosal disruption or trauma of the vaginal canal.

Drug Interactions

Concurrent use with vaginal rings is contraindicated due to potential decreased efficacy.
Can be used safely with other vaginal infection treatments such as miconazole, metronidazole, or tioconazole.
Potential interactions with other vaginal devices should be assessed on a case-by-case basis.
No known systemic drug interactions due to lack of systemic absorption.
May be used concomitantly with hormonal contraceptives (pills, patches, implants, injections).
Compatible with condom use (latex, polyurethane, polyisoprene).
No known interactions with vitamins or herbal supplements but disclose all medications to healthcare providers.
Over-the-counter vaginal products should be discussed with healthcare professionals before concurrent use.
Avoid mixing with incompatible vaginal gels or spermicides without consulting a provider.
No documented impact on pharmacokinetics of other drugs due to local application.
No known inhibitory or inductive effects on cytochrome P450 enzymes or other metabolic pathways.
No known interactions affecting fertility or ovulation.
No interactions altering vaginal flora or microbiome beyond intended pH modulation.
Potential for irritation increased if used with other vaginal irritants or allergens.
Ensure that vaginal medications used concurrently do not alter vaginal pH excessively, reducing contraceptive effectiveness.

Preparations Of The Drug

Phexxi vaginal gel supplied in 5 gram single-dose prefilled applicators.
Active ingredients per dose: Lactic acid USP 1.8% w/w, Citric acid USP 1.0% w/w, Potassium bitartrate USP 0.4% w/w.
Inactive ingredients include glycerin, alginic acid, xanthan gum, sodium hydroxide, benzoic acid, and purified water to optimize gel consistency and stability.
Each applicator is individually sealed in a foil pouch to preserve stability and prevent contamination.
Stored at room temperature, protected from moisture and heat to maintain efficacy.
Single-use applicators designed for intravaginal administration only; do not reuse applicators.
Gel formulation ensures adherence to vaginal mucosa and maintains decreased pH for contraceptive effect.
Packaging designed to facilitate discreet, convenient administration.
Product labeling includes detailed instructions for safe and effective use prior to intercourse.
No hormonal components included; categorized as a non-hormonal topical contraceptive gel.
Manufactured under strict pharmaceutical standards to ensure consistency of active ingredient concentration.
Shelf-life and expiration specified on packaging, critical for maintaining product efficacy.
No preservatives likely to cause systemic effects due to topical use.
Sterility maintained through packaging, but product is non-sterile gel applied topically.