Terazol

One applicator full of the 0.4% vaginal cream should be applied into the vagina at bedtime for 7 days. One applicator full of the 0.8% vaginal cream or one vaginal suppository should be applied at bedtime for 3 days.

Vulvovaginal Candidiasis

Treatment of uncomplicated vulvovaginal candidiasis (mild to moderate, sporadic or infrequent, most likely caused by Candida albicans, occurring in immunocompetent women).1 3 5 15 16 17 18 19 20 21 22 23 24 27 33 37 47 49 65 67 68 A drug of choice.37 47 51 52 53 54 56 57 58 65 67 68

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).47 53 54 56 57 58 67 68 Complicated infections generally require more prolonged treatment than uncomplicated infections.47 66 67 68

Optimal regimens for treatment of vulvovaginal candidiasis caused by Candida other than C. albicans (e.g., C. glabrata, C. krusei) not identified.47 68 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).47 68 69

Contraindications

• Known hypersensitivity to terconazole or any ingredient in the formulation.1

Warnings/Precautions

Sensitivity Reactions

Possible flu-like syndrome, characterized by fever, chills, headache, and/or hypotension and occasionally by vertigo and nausea.45 May be immunoallergenic45 or may be a reaction to the dying fungi (similar to the Jarisch-Herxheimer reaction observed during penicillin therapy for syphilis).46

If irritation, sensitization, fever, chills, or flu-like symptoms occur and appear to be drug related, discontinue and do not reinstitute terconazole therapy.1

Photosensitivity reactions reported following repeated topical application to the skin of 0.8 or 2% terconazole cream and exposure to filtered artificial ultraviolet light; not reported to date following intravaginal administration of 0.4 or 0.8% cream or 80-mg suppositories.1 3

General Precautions

Hydrogenated vegetable oil base contained in terconazole vaginal suppositories may interact with certain rubber or latex products such as vaginal contraceptive diaphragms; concurrent use not recommended.1 Consider use of terconazole vaginal cream as an alternative to the suppositories.43 44

Prior to initial use of terconazole in a woman with signs and symptoms of vulvovaginal candidiasis, confirm the diagnosis by demonstrating yeast or pseudohyphae with direct microscopic examination of vaginal discharge (saline or 10% potassium hydroxide [KOH] wet mount or Gram stain) or by culture.1 47

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.47

If clinical symptoms persist, tests should be repeated to rule out other pathogens and to confirm the original diagnosis.1

Specific Populations

Category C.1

Because terconazole is absorbed systemically following intravaginal administration, manufacturer states the drug should not be used during the first trimester of pregnancy unless the clinician considers it essential to the welfare of the patient.1 CDC and others state that a 7-day regimen of an intravaginal azole antifungal can be used, if necessary, for treatment of vulvovaginal candidiasis in pregnant women.47 67

Distributed into milk in rats;1 not known whether distributed into human milk.1 43 Discontinue nursing or the drug.1

Safety and efficacy not established in children1 <18 years of age.43

Insufficient experience from clinical studies to determine whether patients ≥65 years of age respond differently than younger adults.1 Other clinical experience has not identified age-related differences in response.1

Common Adverse Effects

Headache,1 3 vulvovaginal itching/burning or pain,1 3 dysmenorrhea,1 abdominal pain.1

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

• It is used to treat vaginal infections.
• It may be given to you for other reasons. Talk with the doctor.

• If you have an allergy to terconazole or any other part of Terazol (terconazole vaginal cream).
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.

This medicine may interact with other drugs or health problems.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this medicine with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

General

Discontinue use and do not retreat with terconazole if sensitization, irritation, fever, chills or flu-like symptoms are reported during use.

The base contained in the suppository formulation may interact with certain rubber or latex products, such as those used in vaginal contraceptive diaphragms; therefore concurrent use is not recommended.

Laboratory Tests

If there is lack of response to terconazole, appropriate microbiologic studies (standard KOH smear and/or cultures) should be repeated to confirm the diagnosis and rule out other pathogens.

Drug Interactions

The therapeutic effect of these products is not affected by oral contraceptive usage.

The levels of estradiol (E2) and progesterone did not differ significantly when 0.8% terconazole vaginal cream was administered to healthy female volunteers established on a low dose oral contraceptive.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Studies to determine the carcinogenic potential of terconazole have not been performed.

Terconazole was not mutagenic when tested in vitro for induction of microbial point mutations (Ames test), or for inducing cellular transformation, or in vivo for chromosome breaks (micronucleus test) or dominant lethal mutations in mouse germ cells.

No impairment of fertility occurred when female rats were administered terconazole orally up to 40 mg/kg/day for a three month period.

Pregnancy

Pregnancy Category C

There was no evidence of teratogenicity when terconazole was administered orally up to 40 mg/kg/day (25× the recommended intravaginal human dose of the suppository formulation, 50× the recommended intravaginal human dose of the 0.8% vaginal cream formulation, and 100× the intravaginal human dose of the 0.4% vaginal cream formulation) in rats, or 20 mg/kg/day in rabbits, or subcutaneously up to 20 mg/kg/day in rats.

Dosages at or below 10 mg/kg/day produced no embryotoxicity; however, there was a delay in fetal ossification at 10 mg/kg/day in rats. There was some evidence of embryotoxicity in rabbits and rats at 20–40 mg/kg. In rats, this was reflected as a decrease in litter size and number of viable young and reduced fetal weight. There was also delay in ossification and an increased incidence of skeletal variants.

The no-effect dose of 10 mg/kg/day resulted in a mean peak plasma level of terconazole in pregnant rats of 0.176 mcg/mL which exceeds by 44 times the mean peak plasma level (0.004 mcg/mL) seen in normal subjects after intravaginal administration of terconazole 0.4% vaginal cream, by 30 times the mean peak plasma level (0.006 mcg/mL) seen in normal subjects after intravaginal administration of terconazole 0.8% vaginal cream, and by 17 times the mean peak plasma level (0.010 mcg/mL) seen in normal subjects after intravaginal administration of terconazole 80 mg vaginal suppository. This safety assessment does not account for possible exposure of the fetus through direct transfer to terconazole from the irritated vagina by diffusion across amniotic membranes.

Since terconazole is absorbed from the human vagina, it should not be used in the first trimester of pregnancy unless the physician considers it essential to the welfare of the patient.

Nursing Mothers

It is not known whether this drug is excreted in human milk. Animal studies have shown that rat offspring exposed via the milk of treated (40 mg/kg/orally) dams showed decreased survival during the first few post-partum days, but overall pup weight and weight gain were comparable to or greater than controls throughout lactation. Because many drugs are excreted in human milk, and because of the potential for adverse reaction in nursing infants from terconazole, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

Safety and efficacy in children have not been established.

Geriatric Use

Clinical studies of Terazol® did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.

Terazol® 7 (terconazole) Vaginal Cream 0.4%

One full applicator (5 g) of Terazol® 7 Vaginal Cream (20 mg terconazole) should be administered intravaginally once daily at bedtime for seven consecutive days.

Terazol® 3 (terconazole) Vaginal Cream 0.8%

One full applicator (5 g) of Terazol® 3 Vaginal Cream (40 mg terconazole) should be administered intravaginally once daily at bedtime for three consecutive days.

Terazol® 3 (terconazole) Vaginal Suppositories 80 mg

One Terazol® 3 Vaginal Suppository (80 mg terconazole) should be administered 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 and other pathogens commonly associated with vulvovaginitis ruled out. The therapeutic effect of these products is not affected by menstruation.

A decision should be made to discontinue breastfeeding or discontinue the drug, taking into account the importance of the drug to the mother. Excreted into human milk: Unknown Excreted into animal milk: Yes Comments: -The effects in the nursing infant are unknown. -According to some experts, other antifungal agents may be preferred, particularly while breastfeeding newborn or preterm infants.

Summary of Use during Lactation

Vaginal terconazole has not been studied during breastfeeding. Other antifungal agents may be preferred, especially while nursing a newborn or preterm infant

Drug Levels

Maternal Levels. Relevant published information was not found as of the revision date.

Infant Levels. Relevant published information was not found as of the revision date.

Effects in Breastfed Infants

Relevant published information was not found as of the revision date.

Effects on Lactation and Breastmilk

Relevant published information was not found as of the revision date.

Alternate Drugs to Consider

Clotrimazole, Miconazole

References