CLASSES

Gynecological Antifungals

DEA CLASS

OTC

DESCRIPTION

Imidazole antifungal
Fungicidal against Candida sp.
Single intravaginal dose is effective

COMMON BRAND NAMES

Monistat 1 Simple Therapy, Vagistat-1

HOW SUPPLIED

Monistat 1 Simple Therapy/Vagistat-1 Vaginal Ointment: 6.5%

DOSAGE & INDICATIONS

MAXIMUM DOSAGE

1 applicatorful (300 mg tioconazole/4.6 g ointment) intravaginally/day.

1 applicatorful (300 mg tioconazole/4.6 g ointment) intravaginally/day.

1 applicatorful (300 mg tioconazole/4.6 g ointment) intravaginally/day.

12 years: 1 applicatorful (300 mg tioconazole/4.6 g ointment) intravaginally/day.
1 to 11 years: Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

DOSING CONSIDERATIONS

No dosage adjustment needed.

No dosage adjustment needed.

ADMINISTRATION

Tioconazole is usually administered intravaginally at bedtime as a single-dose treatment.
Wash hands before and after administration.
Read package directions carefully. The applicator should be opened just before use in order to prevent contamination. To use tioconazole vaginal ointment, gently insert the applicator tip high in the vagina and push the plunger to release the ointment into the vagina; gently remove the applicator.

STORAGE

1-Day:
- Store at room temperature (between 59 to 86 degrees F)
Monistat 1 Simple Therapy:
- Store between 68 to 77 degrees F
Vagistat-1:
- Store between 68 to 77 degrees F

CONTRAINDICATIONS / PRECAUTIONS

Tioconazole is contraindicated in patients who have never had a vaginal yeast infection diagnosed by a physician.

Tioconazole is classified as FDA pregnancy risk category C. There are limited data in pregnant women. Tioconazole did not adversely affect fetal viability or growth when administered orally to pregnant rats at doses up to 165 mg/kg/day during the period of organogenesis. However, tioconazole can cause dystocia in rats when treatment is extended through parturition; effects include prolongation of pregnancy, in utero deaths, and impaired pup survival. These effects are only observed with oral doses exceeding 20 mg/kg/day and intravaginal doses greater than 9 mg/kg/day. It is not known if tioconazole crosses the human placenta; however, there is negligible systemic absorption following intravaginal administration. Clinically significant exposure to the fetus is unlikely. According to CDC guidelines, many experts recommend 7 days of therapy with a topical azole preparation for the treatment of vulvovaginal candidiasis that occurs during pregnancy. Because tioconazole is administered as a single-dose treatment and the data regarding use in pregnant women is limited, an alternative antifungal (e.g., clotrimazole, miconazole or nystatin) should be considered. Pregnant women are advised to consult a health care professional prior to use.

There are no data regarding use of tioconazole during breast-feeding; excretion into breast milk is unknown. Systemic absorption following intravaginal administration is negligible. Although it's unlikely to produce detectable concentrations in breast-milk, nursing mothers are advised to consult a health care professional prior to use. Clotrimazole and miconazole may be potential alternatives to consider during breast-feeding. However, site of infection, local susceptibility patterns, and specific microbial susceptibility should be assessed before choosing an alternative agent. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, health care providers are encouraged to report the adverse effect to the FDA.

Patients should be advised not to use tampons, douches, spermicides, or other vaginal products while using tioconazole. Patients should avoid vaginal intercourse during treatment. The base used in tioconazole products may interact with contraceptive devices containing rubber or latex such as condoms, diaphragms, and cervical caps; these devices can be damaged while using tioconazole, and may lead to contraceptive failures or lack of protection from sexually transmitted diseases (STDs). Patients should avoid using condoms or vaginal contraceptive diaphragms for 3 days after treatment with tioconazole. Although tioconazole may be used during menstruation, instruct patients not to use tampons.

If symptoms do not improve within 3 days or remain after 7 days from day of treatment with tioconazole, a physician should be consulted and treatment discontinued. A physician should also be consulted if initial treatment is effective but symptoms recur within 2 months. Recurring yeast infections may be a sign of pregnancy or a serious condition such as AIDS or diabetes. Some patients should not use non-prescription tioconazole products without the supervision of a health care professional; patients with immunosuppression, undergoing chemotherapy, diabetes mellitus, or human immunodeficiency virus (HIV) infection should discuss use of these products with their health care professional prior to self-treatment. Females should not self-treat with intravaginal tioconazole products if the following signs and symptoms are present: back or shoulder pain, lower abdominal pain, chills, fever > 100 degrees F, nausea or vomiting, or foul-smelling vaginal discharge. Such symptoms may be an indication of another vaginal infection or pelvic inflammatory disease. Approximately 20% of all vaginal candidal infections co-exist with another infection. If these symptoms occur during treatment, tioconazole should be discontinued and a physician consulted.

Tioconazole should not be used in patients with a history of azole antifungals hypersensitivity. Hypersensitivity reactions may be due to the various vehicles present in tioconazole formulations.

Safe and effective use of tioconazole has not been established in neonates, infants and children less than 12 years of age.

Avoid ocular exposure to tioconazole. If ocular exposure occurs, treat by immediate flushing the affected eye with cool, clean water. Contact an ophthalmologist if eye irritation persists.

ADVERSE REACTIONS

contact dermatitis / Delayed / 1.0-10.0
vaginal pain / Early / 0-1.0
dyspareunia / Delayed / 0-1.0
dysuria / Early / 0-1.0

pruritus / Rapid / 1.9-6.0
vaginal irritation / Early / 1.9-6.0
nocturia / Early / 0-1.0

DRUG INTERACTIONS

There are no drug interactions associated with Tioconazole products.

PREGNANCY AND LACTATION

Tioconazole is classified as FDA pregnancy risk category C. There are limited data in pregnant women. Tioconazole did not adversely affect fetal viability or growth when administered orally to pregnant rats at doses up to 165 mg/kg/day during the period of organogenesis. However, tioconazole can cause dystocia in rats when treatment is extended through parturition; effects include prolongation of pregnancy, in utero deaths, and impaired pup survival. These effects are only observed with oral doses exceeding 20 mg/kg/day and intravaginal doses greater than 9 mg/kg/day. It is not known if tioconazole crosses the human placenta; however, there is negligible systemic absorption following intravaginal administration. Clinically significant exposure to the fetus is unlikely. According to CDC guidelines, many experts recommend 7 days of therapy with a topical azole preparation for the treatment of vulvovaginal candidiasis that occurs during pregnancy. Because tioconazole is administered as a single-dose treatment and the data regarding use in pregnant women is limited, an alternative antifungal (e.g., clotrimazole, miconazole or nystatin) should be considered. Pregnant women are advised to consult a health care professional prior to use.

There are no data regarding use of tioconazole during breast-feeding; excretion into breast milk is unknown. Systemic absorption following intravaginal administration is negligible. Although it's unlikely to produce detectable concentrations in breast-milk, nursing mothers are advised to consult a health care professional prior to use. Clotrimazole and miconazole may be potential alternatives to consider during breast-feeding. However, site of infection, local susceptibility patterns, and specific microbial susceptibility should be assessed before choosing an alternative agent. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, health care providers are encouraged to report the adverse effect to the FDA.

MECHANISM OF ACTION

Tioconazole exerts its effect by disrupting normal fungal cell membrane permeability. Ergosterol is an essential component of the fungal cell membrane. Tioconazole inhibits ergosterol synthesis by interacting with 14-alpha demethylase, a cytochrome P-450 enzyme necessary for converting lanosterol to ergosterol. Inhibition of ergosterol synthesis results in increased cellular permeability, causing leakage of cellular contents such as phosphorous-containing compounds and potassium.

PHARMACOKINETICS

Tioconazole is administered intravaginally. Systemic absorption after a single intravaginal application in nonpregnant women is negligible.