Boric acid (vaginal)

Contraindications

It is recommended that vaginal boric acid be avoided by pregnant or lactating patients. It is teratogenic at sufficient doses in animals.

Side effects

The most common adverse effect of vaginal boric acid has been found to be temporary vaginal burning (5%). Other side effects of vaginal boric acid have been found to include irritation, itching, redness, bleeding, and erosive changes in a small percentage of users (2.3%). Watery discharge appears to be a common and mild adverse effect of vaginal boric acid, but its frequency is unknown. Another reported side effect is a gritty sensation with sexual intercourse during treatment. The side effects of vaginal boric acid are usually mild and temporary.

The safety of topical boric acid, including its long-term safety, is under-characterized. Boric acid has known toxic properties when taken orally or at high doses. It is also a widely used pesticide. However, vaginal boric acid appears to be safe based on available data. No reports of serious toxicity with vaginal boric acid have been published since the 1880s, when extremely high doses (25 to 100 times higher than present recommended doses) were employed. Since the 1880s, only sporadic and mild side effects have been documented. This has included findings in more than 2,000 women in one study. Nonetheless, it is possible that rare but serious side effects could exist.

Boric acid may be able to cause local tissue injury due to caustic effects.

Overdose

Symptoms of boric acid poisoning, for instance with large amounts of orally ingested boric acid, may include nausea, vomiting, abdominal pain, and diarrhea. More severe symptoms may include blue-green vomit, central nervous system depression, fever, headache, dermatitis or skin eruptions, a "boiled lobster" skin rash, reversible scalp hair loss, weakness, cyanosis, and kidney failure. However, most cases of oral boric acid overdose are asymptomatic. Doses of 15 to 20 grams (0.1–0.5 mg/kg) have been said to be potentially fatal in adults, but findings are inconsistent and there have been cases of individuals consuming 89 grams without death or severe symptoms. The doses of oral boric acid required for adverse effects appear to be much greater than a single 600 mg oral dose. Toxicity of boric acid has also been reported with large amounts applied topically to the skin.

The median lethal doses (LD₅₀) of boric acid in animals have been described. They have been found to be 2.7 to 4 g/kg orally in rats and 1.8 to 2.1 g/kg via intravenous or subcutaneous injection in mice.

Interactions

Vaginal boric acid is thought to have a low risk of interactions with systemic drugs.

Pharmacology

Pharmacodynamics

Boric acid is an antiseptic and has bacteriostatic and fungistatic effects. It has often been described as a weak or mild antimicrobial. The compound is not an antibiotic or antifungal, and in contrast to these agents, has broad-spectrum antimicrobial activity and inhibits multiple different biological processes of microorganisms. As a result, antimicrobial resistance is less likely to develop to boric acid. It has been reported to specifically be active against the gram-positive and gram-negative bacteria, bacteria like staphylococci and streptococci, and the fungi Candida spp. (including Candida albicans and Candida glabrata) and Saccharomyces cerevisiae, among others. It has been said to not be active against all pathogens, for instance mold fungus.

The exact mechanism of action of boric acid is unclear. One hypothesis is that boric acid works via vaginal acidification, raising vaginal pH and thereby creating and environment less hospitable to undesirable microorganisms. However, in studies, its antimicrobial properties have been found to be independent of pH. Boric acid can also inhibit bacterial and fungal biofilms. However, it may not be effective against pre-existing biofilms.

Pharmacokinetics

Boric acid for vaginal infections is indicated for vaginal administration and not for oral administration. Oral administration of boric acid can result in serious toxicity.

Absorption

Boric acid rapidly and completely absorbed from the gastrointestinal tract with oral administration. Its oral bioavailability appears to be almost 100%. Absorption of boric acid through intact skin appears to be minimal. However, application of boric acid to damaged skin can allow for much greater absorption.

In one study, circulating boron levels prior to treatment were undetectable (<0.04 μg/mL), and following 600–1,200 mg/day vaginal boric acid for 1 to 2 weeks, boron levels increased to 0.42 μg/mL. For comparison, normal circulating boron levels are 0.1 to 80 μg/mL, acute boric acid toxicity has been associated with levels of 5.4 to 1,000 μg/mL, concentrations of 80 to 126 μg/mL have been observed without toxicity symptoms or signs, and boric acid levels of less than 200 μg/mL are thought to be safe by many researchers. Based on a case study of one healthy woman in the study, who had boron levels of 0.1 to 0.15 μg/mL, it was estimated that 6% of vaginally administered boric acid is absorbed systemically. Other studies have found undetectable boric acid levels with vaginal boric acid, though the detection threshold may not have been sensitive enough or was not reported at all.

Distribution

Following absorption, boric acid is widely distributed throughout the body. It has shown accumulation in the brain, liver, and kidneys. Its volume of distribution is 0.17 to 0.5 L/kg in humans. The plasma protein binding of boric does not appear to have been reported and hence is unknown.

Metabolism

Boric acid does not undergo appreciable metabolism. No metabolites of boric acid are known.

Elimination

Boric acid is rapidly and primarily eliminated in urine. It is excreted 50% in urine within 12 hours and 90% in urine within 4 days. Small amounts of boric acid are excreted in feces, sweat, and saliva.

Following intravenous injection of 600 mg boric acid in healthy men, the elimination half-life was found to be 21 hours. On the basis of one woman in a study, the elimination half-life of boric acid with vaginal administration has been found to be 10.5 hours. In cases of human poisoning, the elimination half-life of boric acid was 13 to 24 hours.

Chemistry

Boric acid is usually in the form of white crystals, scales, or a white powder. It is colorless, odorless, non-irritating, and does not stain.

The compound is a weak acid. The alkali salts of boric acid are alkaline.

History

Boric acid has been used medically since ancient times. Its discovery in modern times is attributed to the German chemist Johann Joachim Becher in the 1600s. The compound was first prepared, from borax, by the Dutch chemist William Homberg in 1702, and he is often incorrectly said to be the discoverer of boric acid. He marketed it for medical use under the brand name "Homberg's sedative salt" and it was claimed to have sedative, anodyne (analgesic), and antispasmodic effects. Boric acid was first used as an antiseptic in Sweden under the brand names Aseptin (a powder) and Aseptin Amykos (a liquid) and its antiseptic properties were reported and confirmed by British surgeon and scientist Joseph Lister in 1874 and 1875. Subsequently, it became widely used for topical application for its antiseptic properties. It was first used as an intravaginal antiseptic by the late 1800s. The compound was originally thought to be benign and non-toxic, but the toxicity of boric acid became more well known with the publication of serious adverse effects in 1899.

The first clinical study of boric acid for treatment of vulvovaginal candidiasis was published in 1974. Use of boric acid for treatment of Torulopsis glabrata vaginitis was first reported by 1990. A phase 2/3 clinical trial of boric acid versus metronidazole, the Boric Acid, Alternate Solution for Intravaginal Colonization (BASIC) study, was registered in 2014 and was completed in 2016, but the results do not appear to have been published. Clinical studies of boric acid for bacterial vaginosis have been published, but no clinical trials have been published as of 2015.

Society and culture

Names

Boric acid is the generic name of the compound and its JANTooltip Japanese Accepted Name. It does not appear to have an INNTooltip International Nonproprietary Name, USANTooltip United States Adopted Name, USPTooltip United States Pharmacopoeia, or BANTooltip British Approved Name. Boric acid has also been known as boracic acid or as orthoboric acid.

Availability

Boric acid is widely available over-the-counter. The availability of unregulated over-the-counter boric acid has been argued against due to safety concerns. Some have proposed that boric acid should only be prescribed by a medical professional.

Research

A combination of boric acid and the penetration enhancer ethylenediaminetetraacetic acid (EDTA) is being developed under the developmental code name TOL-463 for treatment of bacterial vaginosis and vulvovaginal candidiasis. Following treatment for 7 days, it has been found to cure vulvovaginal candidiasis at rates of 92% as an insert and 81% as a gel and to cure bacterial vaginosis at rates of 59% for the insert and 50% for the gel. Although the bacterial vaginosis cure rates were lower, reported symptom resolution was high for both conditions, with rates of 69 to 93%.

Veterinary medicine

Boric acid has toxic effects in animals similarly to humans and can result in pet poisonings.