Prescribing information (package insert) - Miconazole
DESCRIPTION
Miconazole Nitrate Vaginal Suppositories USP, 200 mg are white to off-white suppositories, each containing the antifungal agent, miconazole nitrate, USP 1-[2,4-Dichloro-β-[(2,4- dichlorobenzyl)oxy] phenethyl]-imidazole mononitrate, 200 mg, in a hydrogenated vegetable oil base. The molecular formula is C18H14Cl4N2O•HNO3; the molecular weight is 479.14 and the structural formula may be represented as follows:
CLINICAL PHARMACOLOGY
Miconazole nitrate exhibits fungicidal activity in vitro against species of the genus Candida. The pharmacologic mode of action is unknown. Following intravaginal administration of miconazole nitrate, small amounts are absorbed. Administration of a single dose of miconazole nitrate vaginal suppositories (100 mg) to healthy subjects resulted in total recovery from the urine and feces of 0.85% (±0.43%) of the administered dose.
Animal studies indicate that the drug crossed the placenta and doses above those used in humans result in embryo and fetotoxicity (80 mg/kg, orally), although this has not been reported in human subjects (See PRECAUTIONS).
In multi-center clinical trials in 440 women with vulvovaginal candidiasis, the efficacy of treatment with the Miconazole Nitrate Vaginal Suppositories USP, 200 mg for 3 days was compared with treatment for 7 days with Miconazole Nitrate Vaginal Cream 2%. The clinical cure rates (free of microbiological evidence and clinical signs and symptoms of candidiasis at 8 to 10 days and 30 to 35 days post therapy) were numerically lower, although not statistically different, with the 3-Day Suppository when compared with the 7-Day Cream.
INDICATIONS AND USAGE
Miconazole Nitrate Vaginal Suppositories USP, 200 mg are indicated for the local treatment of vulvovaginal candidiasis (moniliasis). Effectiveness in pregnancy has not been established. As miconazole nitrate is effective only for candidal vulvovaginitis, the diagnosis should be confirmed by KOH smear and/or cultures. Other pathogens commonly associated with vulvovaginitis (Trichomonas and Haemophilus vaginalis [Gardnerella]) should be ruled out by appropriate laboratory methods.
CONTRAINDICATIONS
Patients known to be hypersensitive to this drug.
PRECAUTIONS
General
Discontinue drug if sensitization or irritation is reported during use. The base contained in the suppository formulation may interact with certain latex products, such as that used in vaginal contraceptive diaphragms. Concurrent use is not recommended. Miconazole Nitrate Vaginal Cream USP, 2% may be considered for use under these conditions.
Laboratory Tests
If there is a lack of response to Miconazole Nitrate Vaginal Suppositories, appropriate microbiological studies (standard KOH smear and/or cultures) should be repeated to confirm the diagnosis and rule out other pathogens.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Long-term animal studies to determine carcinogenic potential have not been performed.
Fertility (Reproduction): Oral administration of miconazole nitrate in rats has been reported to produce prolonged gestation. However, this effect was not observed in oral rabbit studies. In addition, signs of fetal and embryo toxicity were reported in rat and rabbit studies, and dystocia was reported in rat studies after oral doses at and above 80 mg per kg. Intravaginal administration did not produce these effects in rats.
Pregnancy
Since imidazoles are absorbed in small amounts from the human vagina, they should not be used in the first trimester of pregnancy unless the physician considers it essential to the welfare of the patient.
Clinical studies, during which miconazole nitrate vaginal cream and suppositories were used for up to 14 days, were reported to include 541 pregnant patients. Follow-up reports available in 471 of these patients reveal no adverse effects or complications attributable to miconazole nitrate therapy in infants born to these women.
Nursing Mothers
It is not known whether miconazole is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when miconazole nitrate is administered to a nursing woman.
ADVERSE REACTIONS
During clinical studies with Miconazole Nitrate Vaginal Suppositories USP, 200 mg, 301 patients were treated. The incidence of vulvovaginal burning, itching or irritation was 2%. Complaints of cramping (2%) and headaches (1.3%) were also reported. Other complaints (hives, skin rash) occurred with less than a 0.5% incidence. The therapy-related dropout rate was 0.3%.
To report SUSPECTED ADVERSE EVENTS, contact Teva Pharmaceuticals USA, Inc., at 1-888-838-2872 or FDA at 1-800-FDA-1088 or http://www.fda.gov/ for voluntary reporting of adverse reactions.
OVERDOSAGE
Overdosage of miconazole nitrate in humans has not been reported to date. In mice, rats, guinea pigs and dogs, the oral LD50 values were found to be 578.1, greater than 640, 275.9 and greater than 160 mg/kg, respectively.
DOSAGE AND ADMINISTRATION
Miconazole Nitrate Vaginal Suppositories USP, 200 mg: One suppository (miconazole nitrate, 200 mg) is inserted intravaginally once daily at bedtime for three consecutive days. Before prescribing another course of therapy, the diagnosis should be reconfirmed by smears and/or cultures to rule out other pathogens.
HOW SUPPLIED
Miconazole Nitrate Vaginal Suppositories USP, 200 mg are available as elliptically shaped white to off-white suppositories in packages of three with a vaginal applicator NDC 0472-1738-03.
Store at controlled room temperature 15° to 30°C (59° to 86°F).
Manufactured for:
Teva Pharmaceuticals USA, Inc.
Parsippany, NJ 07054
Rev. A 7/2020