Tioconazole (Monograph)

Brand names: 1-Day, Vagistat-1
Drug class: Azoles
ATC class: D01AC07
VA class: GU300
Chemical name: 1-[2-[(2-Chloro-3-thienyl)methoxy]-2-(2,4-dichlorophenyl)ethyl]-1H-imidazole
Molecular formula: C₁₆H₁₃C_l3N₂OS
CAS number: 65899-73-2

Introduction

Antifungal; azole (imidazole derivative).

Uses for Tioconazole

Vulvovaginal Candidiasis

Treatment of uncomplicated vulvovaginal candidiasis (mild to moderate, sporadic or infrequent, most likely caused by Candida albicans, occurring in immunocompetent women). A drug of choice.

Self-medication (OTC use) for treatment of uncomplicated vulvovaginal candidiasis in otherwise healthy, nonpregnant women who have been previously diagnosed by a clinician and are having recurrence of similar symptoms.

Treatment of complicated vulvovaginal candidiasis, including infections that are recurrent (≥4 episodes in 1 year), severe (extensive vulvar erythema, edema, excoriation, fissure formation), caused by Candida other than C. albicans, or occurring in women with underlying medical conditions (uncontrolled diabetes mellitus, HIV infection, immunosuppressive therapy, pregnancy). Complicated infections generally require more prolonged treatment than uncomplicated infections.

Optimal regimens for treatment of vulvovaginal candidiasis caused by Candida other than C. albicans (e.g., C. glabrata, C. krusei) not identified. CDC and others state these infections may respond to an intravaginal azole antifungal given for 7–14 days or to a 14-day regimen of intravaginal boric acid (not commercially available in the US).

Tioconazole Dosage and Administration

Administration

Intravaginal Topical Administration

Administer intravaginally as a 6.5% ointment using the prefilled applicator provided by the manufacturer.

Vaginal ointment is for intravaginal administration only; do not administer orally. Avoid contact with the eyes.

Administer dose intravaginally high in the vaginal vault at bedtime.

Open applicator just prior to administration to prevent contamination.

Dosage

Pediatric Patients

Uncomplicated Vulvovaginal Candidiasis

Intravaginal

Children ≥12 years of age: One applicatorful of 6.5% ointment (approximately 300 mg of tioconazole) as a single dose at bedtime. May be used for self-medication.

If clinical symptoms do not improve within 3 days, persist for >7 days, or recur within 2 months, discontinue self-medication and consult a clinician. Confirm diagnosis and rule out other pathogens and conditions that may predispose a patient to recurrent vaginal fungal infections.

HIV-infected Adolescents

Intravaginal

Use same regimen recommended for other patients. Some experts recommend a duration of 3–7 days. Maintenance regimen of an intravaginal azole can be considered for those with recurrent episodes; routine primary or secondary prophylaxis (long-term suppressive or chronic maintenance therapy) not recommended.

Complicated Vulvovaginal Candidiasis

Recurrent Vulvovaginal Infections Caused by Candida albicans

Intravaginal

Adolescents: CDC and others recommend an initial intensive regimen (7–14 days of an intravaginal azole or 3-dose regimen of oral fluconazole) to achieve mycologic remission, followed by an appropriate maintenance regimen (6-month regimen of once-weekly oral fluconazole or, alternatively, an intravaginal azole given intermittently).

Other Complicated Vulvovaginal Infections

Intravaginal

Adolescents: CDC and others recommend 7–14 days of an intravaginal azole for vulvovaginal candidiasis that is severe, caused by Candida other than C. albicans, or occurring in those with underlying medical conditions.

Adults

Uncomplicated Vulvovaginal Candidiasis

Intravaginal

One applicatorful of 6.5% ointment (approximately 300 mg of tioconazole) as a single dose at bedtime. May be used for self-medication.

If clinical symptoms do not improve within 3 days, persist for >7 days, or recur within 2 months, discontinue self-medication and consult a clinician. Confirm diagnosis and rule out other pathogens and conditions that may predispose a patient to recurrent vaginal fungal infections.

HIV-infected Adults

Intravaginal

Use same regimen recommended for other patients. Some experts recommend a duration of 3–7 days. Maintenance regimen of an intravaginal azole can be considered for those with recurrent episodes; routine primary or secondary prophylaxis (long-term suppressive or chronic maintenance therapy) not recommended.

Complicated Vulvovaginal Candidiasis

Recurrent Vulvovaginal Infections Caused by Candida albicans

Intravaginal

CDC and others recommend an initial intensive regimen (7–14 days of an intravaginal azole or 3-dose regimen of oral fluconazole) to achieve mycologic remission, followed by an appropriate maintenance regimen (6-month regimen of once-weekly oral fluconazole or, alternatively, an intravaginal azole given intermittently).

Other Complicated Vulvovaginal Infections

Intravaginal

CDC and others recommend 7–14 days of an intravaginal azole for vulvovaginal candidiasis that is severe, caused by Candida other than C. albicans, or occurring in women with underlying medical conditions.

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time.

Renal Impairment

No specific dosage recommendations at this time.

Geriatric Patients

No specific dosage recommendations at this time.

Cautions for Tioconazole

Contraindications

Known hypersensitivity to tioconazole, other imidazoles, or any ingredient in the formulation.

Warnings/Precautions

Warnings

Use of Latex or Rubber Products

Tioconazole vaginal ointment contains petroleum base that can weaken latex or rubber products (including condoms and vaginal contraceptive diaphragms). Use of such products within 72 hours following intravaginal tioconazole treatment not recommended.

Sensitivity Reactions

Hypersensitivity Reactions

Contact dermatitis reported following topical application of tioconazole or other imidazole-derivative azole antifungals.

Possible cross-sensitization among the imidazoles.

General Precautions

Selection and Use of Antifungals for Vulvovaginal Candidiasis

Prior to initial use in a woman with signs and symptoms of vulvovaginal candidiasis, confirm diagnosis by direct microscopic examination of vaginal discharge (saline or potassium hydroxide [KOH] wet mount or Gram stain) and/or cultures.

Candida identified by culture in the absence of symptoms is not an indication for antifungal treatment since approximately 10–20% of women harbor Candida or other yeasts in the vagina.

If clinical symptoms persist after treatment, repeat tests to rule out other pathogens, confirm the original diagnosis, and rule out other conditions that may predispose a patient to recurrent vaginal fungal infections (e.g., HIV infection).

Do not use for self-medication in women who are or think they may be pregnant or in those with diabetes mellitus, HIV infection, or HIV exposure.

Specific Populations

Pregnancy

Category C.

Lactation

Not known whether tioconazole is distributed into milk after intravaginal administration; temporarily discontinue nursing during treatment.

Pediatric Use

Safety and efficacy not established in children <12 years of age.

Common Adverse Effects

Vulvovaginal burning, irritation, vaginitis, pruritus, headache.

Drug Interactions

Weak inducer of CYP450 isoenzymes.

Drugs Metabolized by Hepatic Microsomal Enzymes

Potential pharmacokinetic interaction with drugs metabolized by CYP450 isoenzymes; interaction unlikely with usual single-dose intravaginal tioconazole regimen since only low amounts of the drug absorbed systemically.

Specific Drugs

Tioconazole Pharmacokinetics

Absorption

Bioavailability

Following intravaginal administration, only small amounts absorbed systemically; peak plasma concentrations usually attained within 2–24 hours.

Distribution

Extent

Unabsorbed drug persists in vaginal fluid for 24–72 hours following an intravaginal dose.

Not known whether tioconazole is distributed into milk.

Elimination

Elimination Route

Does not appear to be metabolized in vaginal fluid. After oral administration of radiolabeled tioconazole, systemically absorbed drug excreted in urine as metabolites (25–27% of the oral dose) and in feces as unchanged drug (59% of the oral dose).

Stability

Storage

Intravaginal

Ointment

15–30°C; expires 3 years following the date of manufacture.

Actions and Spectrum

• Imidazole-derivative azole antifungal.

• Usually fungistatic in action; can be fungicidal at high concentrations or against very susceptible organisms (e.g., Candida).

• Presumably exerts its antifungal activity by altering cellular membranes, resulting in increased membrane permeability, secondary metabolic effects, and growth inhibition. Interferes with ergosterol synthesis probably via inhibition of C-14 demethylation of sterol intermediates (e.g., lanosterol).

• Spectrum of antifungal activity includes many fungi, including yeasts and dermatophytes. Also has in vitro activity against some gram-positive and gram-negative bacteria, Trichomonas, and Chlamydia.

• Candida: Active in vitro and in vivo against C. albicans, C. glabrata (formerly Torulopsis glabrata), C. krusei, C. parapsilosis, C. pseudotropicalis, and C. tropicalis.

• Dermatophytes and other fungi: Active in vitro against Epidermophyton floccosum, E. stockdaleae, Microsporum canis, M. gypseum, Trichophyton mentagrophytes, T. rubrum, T. tonsurans. Also active against Aspergillus and Cryptococcus neoformans.

• Bacteria: Active in vitro against Corynebacterium minutissimum, Enterococcus faecalis (formerly Streptococcus faecalis), Gardnerella vaginalis (formerly Haemophilus or Corynebacterium vaginalis), H. ducreyi , Helicobacter pylori, , Mobiluncus, Moraxella catarrhalis (formerly Branhamella catarrhalis), Neisseria gonorrhoeae, N. meningitidis, Staphylococcus aureus, S. epidermidis, and some streptococci.

• Other organisms: Active against Chlamydia trachomatis, Lymphogranuloma venereum, and Trichomonas vaginalis.

• C. albicans, C. glabrata, C. krusei, C. tropicalis, and C. parapsilosis with reduced susceptibility to tioconazole reported.

• Cross-resistance can occur among the azole antifungals.

Advice to Patients

• Importance of reading and understanding manufacturer’s patient instructions regarding use of applicator for intravaginal administration.

• Not for self-medication in women who have never had a vaginal yeast infection diagnosed by a clinician.

• Not for self-medication in women who think they are pregnant or have been exposed to HIV.

• Importance of discontinuing self-medication of vulvovaginal candidiasis and consulting clinician if fever, abdominal pain, or foul-smelling discharge develops; if symptoms do not improve within 3 days, if condition persists beyond 7 days, or if symptoms recur within 2 months.

• Importance of informing clinicians if irritation, sensitization, fever, chills, or flu-like symptoms occur.

• Advise patients that a single intravaginal dose of tioconazole 6.5% ointment generally is effective, but complete relief may not occur on the day of treatment. Most women experience some relief of symptoms within 1 day and complete relief within 7 days.

• Importance of not using latex or rubber products such as condoms or vaginal contraceptive diaphragms within 72 hours following tioconazole treatment.

• Importance of not having vaginal intercourse, douching, using spermicides, or other vaginal products after an intravaginal dose of tioconazole.

• If used during menstruation, importance of using sanitary napkins instead of vaginal tampons.

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, and concomitant illnesses, including diabetes mellitus and HIV infection.

• Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.

• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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