Rx Drugs Info

terazol 3 (terconazolecream 
terazol 7 (terconazolecream 
terazol 3 (terconazolesuppository 
[ORTHO-McNEIL PHARMACEUTICAL, INC.]

DESCRIPTION

TERAZOL® 7 (terconazole) Vaginal Cream 0.4% is a white to off-white, water washable cream for intravaginal administration containing 0.4% of the antifungal agent terconazole, cis -1-[p-[[2-(2,4-Dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]-4-isopropylpiperazine, compounded in a cream base consisting of butylated hydroxyanisole, cetyl alcohol, isopropyl myristate, polysorbate 60, polysorbate 80, propylene glycol, stearyl alcohol, and purified water.

TERAZOL® 3 (terconazole) Vaginal Cream 0.8% is a white to off-white, water washable cream for intravaginal administration containing 0.8% of the antifungal agent terconazole, cis-1-[p-[[2-(2,4-Dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]-4-isopropylpiperazine, compounded in a cream base consisting of butylated hydroxyanisole, cetyl alcohol, isopropyl myristate, polysorbate 60, polysorbate 80, propylene glycol, stearyl alcohol, and purified water.

TERAZOL® 3 (terconazole) Vaginal Suppositories are white to off-white suppositories for intravaginal administration containing 80 mg of the antifungal agent terconazole, cis-1-[p-[[2-(2,4-Dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]-4-isopropylpiperazine, in triglycerides derived from coconut and/or palm kernel oil (a base of hydrogenated vegetable oils) and butylated hydroxyanisole.

The structural formula of terconazole is as follows:

TERCONAZOLE

Image from Drug Label Content

C26H31Cl2N5O3

Terconazole, a triazole derivative, is a white to almost white powder with a molecular weight of 532.47. It is insoluble in water; sparingly soluble in ethanol; and soluble in butanol.

CLINICAL PHARMACOLOGY

Following intravaginal administration of terconazole in humans, absorption ranged from 5–8% in three hysterectomized subjects and 12–16% in two non-hysterectomized subjects with tubal ligations.

Following daily intravaginal administration of 0.8% terconazole 40 mg (0.8% cream × 5 g) for seven days to normal humans, plasma concentrations were low and gradually rose to a daily peak (mean of 5.9 ng/mL or 0.006 mcg/mL) at 6.6 hours.

Results from similar studies in patients with vulvovaginal candidiasis indicate that the slow rate of absorption, the lack of accumulation, and the mean peak plasma concentration of terconazole was not different from that observed in healthy women. The absorption characteristics of terconazole 0.8% in pregnant or non-pregnant patients with vulvovaginal candidiasis were also similar to those found in normal volunteers.

Following oral (30 mg) administration of 14C-labelled terconazole, the harmonic half-life of elimination from the blood for the parent terconazole was 6.9 hours (range 4.0–11.3). Terconazole is extensively metabolized; the plasma AUC for terconazole compared to the AUC for total radioactivity was 0.6%. Total radioactivity was eliminated from the blood with a harmonic half-life of 52.2 hours (range 44–60). Excretion of radioactivity was both by renal (32–56%) and fecal (47–52%) routes.

In vitro , terconazole is highly protein bound (94.9%) and the degree of binding is independent of drug concentration.

Photosensitivity reactions were observed in some normal volunteers following repeated dermal application of terconazole 2.0% and 0.8% creams under conditions of filtered artificial ultraviolet light.

Photosensitivity reactions have not been observed in U.S. and foreign clinical trials in patients who were treated with terconazole suppositories or vaginal cream (0.4% and 0.8%).

Microbiology

Terconazole exhibits fungicidal activity in vitro against Candida albicans. Antifungal activity has also been demonstrated against other fungi. The MIC values of terconazole against most Lactobacillus spp. typically found in the human vagina were ≥128 mcg/mL; therefore these beneficial bacteria are not affected by drug treatment.

The exact pharmacologic mode of action of terconazole is uncertain; however, it may exert its antifungal activity by the disruption of normal fungal cell membrane permeability. No resistance to terconazole has developed during successive passages of C. albicans.

INDICATIONS AND USAGE

TERAZOL® 7 (terconazole) Vaginal Cream 0.4%, TERAZOL® 3 (terconazole) Vaginal Cream 0.8% and TERAZOL® 3 (terconazole) Vaginal Suppositories 80 mg are indicated for the local treatment of vulvovaginal candidiasis (moniliasis). As these products are effective only for vulvovaginitis caused by the genus Candida, the diagnosis should be confirmed by KOH smears and/or cultures.

CONTRAINDICATIONS

Patients known to be hypersensitive to terconazole or to any of the components of the cream or suppositories.

WARNINGS

None.

PRECAUTIONS

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

TERAZOL® 7 (terconazole) Vaginal Cream 0.4% and TERAZOL® 3 (terconazole) Vaginal Suppositories 80 mg

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

TERAZOL® 3 (terconazole) Vaginal Cream 0.8%

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

Carcinogenesis

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

Mutagenicity

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.

Impairment of Fertility

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

Pregnancy

Teratogenic Effects

Pregnancy Category C

There was no evidence of teratogenicity when terconazole was administered orally up to 40 mg/kg/day (25x the recommended intravaginal human dose of the suppository formulation, 50x the recommended intravaginal human dose of the 0.8% vaginal cream formulation, and 100x 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.

ADVERSE REACTIONS

TERAZOL® 7 (terconazole) Vaginal Cream 0.4%

During controlled clinical studies conducted in the United States, 521 patients with vulvovaginal candidiasis were treated with terconazole 0.4% vaginal cream. Based on comparative analyses with placebo, the adverse experiences considered most likely related to terconazole 0.4% vaginal cream were headache (26% vs. 17% with placebo) and body pain (2.1% vs. 0% with placebo). Vulvovaginal burning (5.2%), itching (2.3%) or irritation (3.1%) occurred less frequently with terconazole 0.4% vaginal cream than with the vehicle placebo. Fever (1.7% vs. 0.5% with placebo) and chills (0.4% vs. 0.0% with placebo) have also been reported. The therapy-related dropout rate was 1.9%. The adverse drug experience on terconazole most frequently causing discontinuation was vulvovaginal itching (0.6%), which was lower than the incidence for placebo (0.9%).

TERAZOL® 3 (terconazole) Vaginal Cream 0.8%

During controlled clinical studies conducted in the United States, patients with vulvovaginal candidiasis were treated with terconazole 0.8% vaginal cream for three days. Based on comparative analyses with placebo and a standard agent, the adverse experiences considered most likely related to terconazole 0.8% vaginal cream were headache (21% vs. 16% with placebo) and dysmenorrhea (6% vs. 2% with placebo). Genital complaints in general, and burning and itching in particular, occurred less frequently in the terconazole 0.8% vaginal cream 3 day regimen (5% vs. 6%–9% with placebo). Other adverse experiences reported with terconazole 0.8% vaginal cream were abdominal pain (3.4% vs. 1% with placebo) and fever (1% vs. 0.3% with placebo). The therapy-related dropout rate was 2.0% for the terconazole 0.8% vaginal cream. The adverse drug experience most frequently causing discontinuation of therapy was vulvovaginal itching, 0.7% with the terconazole 0.8% vaginal cream group and 0.3% with the placebo group.

TERAZOL® 3 (terconazole) Vaginal Suppositories 80 mg

During controlled clinical studies conducted in the United States, 284 patients with vulvovaginal candidiasis were treated with terconazole 80 mg vaginal suppositories. Based on comparative analyses with placebo (295 patients), the adverse experiences considered adverse reactions most likely related to terconazole 80 mg vaginal suppositories were headache (30.3% vs. 20.7% with placebo) and pain of the female genitalia (4.2% vs. 0.7% with placebo). Adverse reactions that were reported but were not statistically significantly different from placebo were burning (15.2% vs. 11.2% with placebo) and body pain (3.9% vs. 1.7% with placebo). Fever (2.8% vs. 1.4% with placebo) and chills (1.8% vs. 0.7% with placebo) have also been reported. The therapy-related dropout rate was 3.5% and the placebo therapy-related dropout rate was 2.7%. The adverse drug experience on terconazole most frequently causing discontinuation was burning (2.5% vs. 1.4% with placebo) and pruritus (1.8% vs. 1.4% with placebo).

OVERDOSAGE

Overdose of terconazole in humans has not been reported to date. In the rat, the oral LD 50 values were found to be 1741 and 849 mg/kg for the male and female, respectively. The oral LD 50 values for the male and female dog were ≅1280 and ≥640 mg/kg, respectively.

DOSAGE AND ADMINISTRATION

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.

HOW SUPPLIED

TERAZOL® 7 (terconazole) Vaginal Cream 0.4% is available in 45g (NDC 0062-5350-01) tubes with an ORTHO* Measured-Dose Applicator. Store at Controlled Room Temperature 15–30°C (59–86°F).

TERAZOL® 3 (terconazole) Vaginal Cream 0.8% is available in 20g (NDC 0062-5356-01) tubes with an ORTHO* Measured-Dose Applicator. Store at Controlled Room Temperature 15–30°C (59–86°F).

TERAZOL® 3 (terconazole) Vaginal Suppositories 80 mg are available as 2.5g, elliptically-shaped white to off-white suppositories in packages of three (NDC 0062-5351-01) with a vaginal applicator. Store at Controlled Room Temperature 15–30°C (59–86°F).

Rx Only.

*Trademark

ORTHO-McNEIL (logo)

ORTHO-McNEIL PHARMACEUTICAL, INC.
Raritan, New Jersey 08869

© OMP 1998

Printed in U.S.A.

Rev April 2003

642-10-300-2

TERAZOL® 7 VAGINAL CREAM 0.4%
(terconazole)

TERAZOL® 3 VAGINAL CREAM 0.8%
(terconazole )

PATIENT INSTRUCTIONS

Filling the Applicator:

1.
Remove the cap from the tube.
2.
Use the pointed tip on the top of the cap to puncture the seal on the tube.
3.
Screw the applicator onto the tube.
4.
Squeeze the tube from the bottom and fill the applicator until the plunger stops.
5.
Unscrew the applicator from the tube.
  
Illustration of cap puncturing tube
  
Illustration of applicator screwed onto tube

Using the Applicator:

1.
Lie on your back with your knees drawn up toward your chest.
  
Illustration of lower extremities.
2.
Holding the applicator by the ribbed end of the barrel, insert the filled applicator into the vagina as far as it will comfortably go.
3.
Slowly press the plunger of the applicator to release the cream into the vagina.
4.
Remove the applicator from the vagina.
5.
Apply one applicatorful each night for as many days at bedtime, as directed by your doctor.

Cleaning the Applicator: (Does not apply to sample applicators, which are for one time use only)

After each use, you should thoroughly clean the applicator by following the procedure below:

1.
Pull the plunger out of the barrel.
2.
Wash the pieces with lukewarm, soapy water, and dry them thoroughly.
3.
Put the applicator back together by gently pushing the plunger into the barrel as far as it will go.
  
Illustration – separate plunger from barrel

NOTE: Store the cream at Controlled Room Temperature 15–30°C (59–86°F). See end flap for lot number and expiration date.

U.S. Patent No. D-279,504


TERAZOL ® 3 VAGINAL SUPPOSITORIES 80mg
(terconazole)

Three oval suppositories, for use inside the vagina only.

Designed to be inserted into the vagina.


HOW TO USE:

Place one suppository into the vagina each night at bedtime, for 3 nights, as directed by your doctor. The TERAZOL Suppository is self-lubricating and may be inserted with or without the applicator.

A.
InsertionWith the Applicator
1.
Filling the applicator
  • Break off suppository from the plastic strip.
  • Pull the plastic completely apart at the notched end.
  • Place the flat end of the suppository into the open end of the applicator as shown. You are now ready to insert the suppository into the vagina.
    Illustration 1
    Illustration 2
2.
Using the applicator
  • Lie on your back with your knees drawn up toward your chest.
  • Holding the applicator by the ribbed end of the barrel, gently insert it into the vagina as far as it will comfortably go.
  • Press the plunger to release the suppository into the vagina.
  • Remove the applicator from the vagina.
    Illustration of lower extremities
3.
Cleaning the applicator (Does not apply to sample applicators, which are for one time use only)
After each use, you should thoroughly clean the applicator by following the procedure below:
  • Pull the plunger out of the barrel.
  • Wash both pieces with lukewarm, soapy water, and dry them thoroughly.
  • Put the applicator back together by gently pushing the plunger into the barrel as far as it will go.
B.
InsertionWithout the Applicator

NOTE: Store the suppositories at Controlled Room Temperature 15–30°C (59–86°F). See end flap for lot number and expiration date.

U.S. Patent No. D-279,504


A WORD ABOUT YEAST INFECTIONS

Why Do Yeast Infections Occur?

Yeast infections are caused by an organism called Candida (KAN di duh). It may be present in small and harmless amounts in the mouth, digestive tract, and vagina. Sometimes the natural balance of the vagina becomes upset. This may lead to rapid growth of Candida, which results in a yeast infection. Symptoms of a yeast infection include itching, burning, redness, and an abnormal discharge.

Your doctor can make the diagnosis of a yeast infection by evaluating your symptoms and looking at a sample of the discharge under the microscope.


How Can I Prevent Yeast Infections?

Certain factors may increase your chance of developing a yeast infection. These factors don't actually cause the problem, but they may create a situation that allows the yeast to grow rapidly.

Controlling these factors can help eliminate yeast infections and may prevent them from coming back.


Some Other Helpful Tips:

1.
For best results, be sure to use the medication as prescribed by your doctor, even if you feel better quickly.
2.
Avoid sexual intercourse, if your doctor advises you to do so. The suppository formulation (not the cream) may damage the diaphragm. Therefore, use of the diaphragm during therapy with the suppository is not recommended. Consult your physician.
3.
If your partner has any penile itching, redness, or discomfort, he should consult his physician and mention that you are being treated for a yeast infection.
4.
You can use the medication even if you are having your menstrual period. However, you should not use tampons because they may absorb the medication. Instead, use external pads or napkins until you have finished your medication. You may also wish to wear a sanitary napkin if the vaginal medication leaks.
5.
Dry the genital area thoroughly after showering, bathing, or swimming. Change out of a wet bathing suit or damp exercise clothes as soon as possible. A dry environment is less likely to encourage the growth of yeast.
6.
Wipe from front to rear (away from the vagina) after a bowel movement.
7.
Don't douche unless your doctor specifically tells you to do so. Douching may disturb the vaginal balance.
8.
Don't scratch if you can help it. Scratching can cause more irritation and spread the infection.
9.
Discuss with your physician any medication you are already taking. Certain types of medication can make your vagina more susceptible to infection.
10.
Eat nutritious meals to promote your general health.

ORTHO-McNEIL (logo)

ORTHO-McNEIL PHARMACEUTICAL, INC.
Raritan, New Jersey 08869

© OMP 1998

Printed in U.S.A.

Rev April 2003

642-10-300-2


Terazol 3 (terconazole)
PRODUCT INFO
Product Code 0062-5356 Dosage Form CREAM
Route Of Administration VAGINAL DEA Schedule
INGREDIENTS
Name (Active Moiety) Type Strength
terconazole (terconazole) Active 8 MILLIGRAM  In 1 GRAM
butylated hydroxyanisole Inactive  
cetyl alcohol Inactive  
isopropyl myristate Inactive  
polysorbate 60 Inactive  
polysorbate 80 Inactive  
propylene glycol Inactive  
stearyl alcohol Inactive  
water Inactive  
IMPRINT INFORMATION
Characteristic Appearance Characteristic Appearance
Color Score
Shape Symbol
Imprint Code Coating
Size
PACKAGING
# NDC Package Description Multilevel Packaging
1 0062-5356-01 20 GRAM In 1 TUBE, WITH APPLICATOR None

Terazol 7 (terconazole)
PRODUCT INFO
Product Code 0062-5350 Dosage Form CREAM
Route Of Administration VAGINAL DEA Schedule
INGREDIENTS
Name (Active Moiety) Type Strength
terconazole (terconazole) Active 4 MILLIGRAM  In 1 GRAM
butylated hydroxyanisole Inactive  
cetyl alcohol Inactive  
isopropyl myristate Inactive  
polysorbate 60 Inactive  
polysorbate 80 Inactive  
propylene glycol Inactive  
stearyl alcohol Inactive  
water Inactive  
IMPRINT INFORMATION
Characteristic Appearance Characteristic Appearance
Color Score
Shape Symbol
Imprint Code Coating
Size
PACKAGING
# NDC Package Description Multilevel Packaging
1 0062-5350-01 45 GRAM In 1 TUBE, WITH APPLICATOR None

Terazol 3 (terconazole)
PRODUCT INFO
Product Code 0062-5351 Dosage Form SUPPOSITORY
Route Of Administration VAGINAL DEA Schedule
INGREDIENTS
Name (Active Moiety) Type Strength
terconazole (terconazole) Active 80 MILLIGRAM  In 1 SUPPOSITORY
coconut oil Inactive  
palm kernel oil Inactive  
butylated hydroxyanisole Inactive  
IMPRINT INFORMATION
Characteristic Appearance Characteristic Appearance
Color Score
Shape Symbol
Imprint Code Coating
Size
PACKAGING
# NDC Package Description Multilevel Packaging
1 0062-5351-01 3 SUPPOSITORY In 1 DOSE PACK None

Revised: 03/2007ORTHO-McNEIL PHARMACEUTICAL, INC.

Data are from FDA and U.S. National Library of Medicine.