TERCONAZOLE

Main information

  • Trade name:
  • TERCONAZOLE- terconazole suppository
  • Composition:
  • Terconazole 80 mg
  • Administration route:
  • VAGINAL
  • Prescription type:
  • PRESCRIPTION DRUG
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • TERCONAZOLE- terconazole suppository
    United States
  • Language:
  • English

Therapeutic information

  • Therapeutic indications:
  • Terconazole Vaginal Suppositories, 80 mg is indicated for the local treatment of vulvovaginal candidiasis (moniliasis). As this product is effective only for vulvovaginitis caused by the genus Candida , the diagnosis should be confirmed by KOH smears and/or cultures. Patients known to be hypersensitive to terconazole or to any of the components of the suppositories.
  • Product summary:
  • Terconazole Vaginal Suppositories 80 mg are available as 2.5 g, elliptically-shaped white to off-white suppositories in packages of three with a vaginal applicator. NDC 0713-0552-73 Store at 20°- 25°C (68°- 77°F) [see USP Controlled Room Temperature].

Status

  • Source:
  • DailyMed - NLM - National Library of Medicine
  • Authorization status:
  • Abbreviated New Drug Application
  • Authorization number:
  • 0713-0552-73
  • Last update:
  • 25-05-2019

Summary of Product characteristics: dosage, interactions, side effects

TERCONAZOLE- terconazole suppository

G & W Laboratories, Inc.

----------

Terconazole

Vaginal Suppositories 80 mg

Rx Only

DESCRIPTION

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

H Cl

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

Abs orption

Following a single intravaginal application of a suppository containing 240 mg

C-terconazole to

healthy women, approximately 70% (range: 64 to 76%) of terconazole remains in the vaginal area

during the suppository retention period (16 hours); approximately 10% (range: 5 to 16%) of the

administered radioactivity was absorbed systemically over 7 days. Maximum plasma concentrations of

terconazole occur 5 to 10 hours after intravaginal application of the cream or suppository. Systemic

exposure to terconazole is approximately proportional to the applied dose, whether as the cream or

suppository. The rate and extent of absorption of terconazole are similar in patients with vulvovaginal

candidiasis (pregnant or non-pregnant) and healthy subjects.

Dis tribution

Terconazole is highly protein bound (94.9%) in human plasma and the degree of binding is independent

of drug concentration over the range of 0.01 to 5.0 mcg/mL.

Metabolis m

Systemically absorbed terconazole is extensively metabolized (>95%).

Elimination

Across various studies in healthy women, after single or multiple intravaginal administration of

terconazole as the cream or suppository/ovule, the mean elimination half-life of unchanged terconazole

ranged from 6.4 to 8.5 hours. Following a single intravaginal administration of a suppository containing

240 mg

C-terconazole to hysterectomized or tubal ligated women, approximately 3 to 10% (mean ±

SD: 5.7 ± 3.0%) of the administered radioactivity was eliminated in the urine and 2.0 to 6% (mean ± SD:

4.2 ± 1.6%) was eliminated in the feces during the 7-day collection period.

Multiple Dosing

There is no significant increase in maximum plasma concentration or overall exposure (AUC) after

multiple daily applications of the cream for 7 days or suppositories for 3 days.

Photosensitivity reactions were observed in some normal volunteers following repeated dermal

application of terconazole 2% 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

Mechanism of action

Terconazole, an azole antifungal agent, inhibits fungal cytochrome P-450-mediated 14 alpha-lanosterol

demethylase enzyme. This enzyme functions to convert lanosterol to ergosterol. The accumulation of

14 alpha-methyl sterols correlates with the subsequent loss of ergosterol in the fungal cell wall and

may be responsible for the antifungal activity of terconazole. Mammalian cell demethylation is less

sensitive to terconazole inhibition.

Activity in vitro

Terconazole exhibits antifungal activity in vitro against Candida albicans and other Candida species.

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.

INDICATIONS AND USAGE

Terconazole Vaginal Suppositories, 80 mg is indicated for the local treatment of vulvovaginal

candidiasis (moniliasis). As this product is 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 suppositories.

WARNINGS

Anaphylaxis and toxic epidermal necrolysis have been reported during terconazole therapy.

Terconazole therapy should be discontinued if anaphylaxis or toxic epidermal necrolysis develops.

PRECAUTIONS

General

For vulvovaginal use only. Terconazole is not for ophthalmic or oral use. 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 or latex condoms; 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 this product is not affected by oral contraceptive usage.

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

(25× the recommended intravaginal human dose of the suppository 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

to 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 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.

Terconazole may be used during the second and third trimester if the potential benefit outweighs the

possible risks to the fetus.

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 terconazole vaginal suppositories 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

Adverse Reactions from Clinical Trials

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed

in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug

and may not reflect the rates observed in clinical practice.

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 have also been 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 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).

Post-marketing Experience

The following adverse drug reactions have been first identified during post-marketing experience with

terconazole:. Because these reactions are reported voluntarily from a population of uncertain size, it is

not always possible to reliably estimate their frequency or establish a causal relationship to drug

exposure.

General: Asthenia, Influenza-Like Illness consisting of multiple listed reactions including fever and

chills, nausea, vomiting, myalgia, arthralgia, malaise

Immune: Hypersensitivity, Anaphylaxis, Face Edema

Nervous: Dizziness

Respiratory: Bronchospasm

Skin: Rash, Toxic Epidermal Necrolysis, Urticaria

To report SUSPECTED ADVERSE REACTIONS, contact G&W Laboratories, Inc. at 1-800-

922-1038 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

OVERDOSAGE

In the rat, the oral LD values were found to be 1741 and 849 mg/kg for the male and female,

respectively. The oral LD values for the male and female dog were

1280 and ≥640 mg/kg,

respectively.

In the event of oral ingestion of suppository or cream, supportive and symptomatic measures should be

carried out. If the cream is accidentally applied to the eyes, wash with clean water or saline and seek

medical attention if symptoms persist.

DOSAGE AND ADMINISTRATION

One Terconazole 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 terconazole vaginal suppositories is not affected by menstruation.

HOW SUPPLIED

Terconazole Vaginal Suppositories 80 mg are available as 2.5 g, elliptically-shaped white to off-white

suppositories in packages of three with a vaginal applicator. NDC 0713-0552-73

Store at 20°- 25°C (68°- 77°F) [see USP Controlled Room Temperature].

Manufactured by:

G&W Laboratories, Inc.

South Plainfield, NJ 07080

Issued 03/2015

8-0552GW1

PATIENT INSTRUCTIONS

Terconazole Vaginal

Suppositories 80 mg

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 terconazole vaginal suppository is self-lubricating and may be inserted with or without the

applicator.

A. Insertion with 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.

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.

3. Cleaning the applicator

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. Insertion without the applicator

Lie on your back with your knees drawn up toward your chest.

Place the suppository on the tip of your finger as shown.

Insert the suppository gently into the vagina as far as it will comfortably go.

NOTE: Store the suppositories at 20°-25°C (68°-77°F) [see USP Controlled Room Temperature]. See

end flap of carton or suppository label for lot number and expiration date.

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.

Clothing: Tight jeans, nylon underwear, pantyhose, and wet bathing suits can hold in heat and

moisture (two conditions in which yeast organisms thrive). Looser pants or skirts, 100% cotton

underwear, and stockings may help avoid this problem.

Diet: Cutting down on sweets, milk products, and artificial sweeteners may reduce the risk of yeast

infections.

Antibiotics: Antibiotics work by eliminating disease-causing organisms. While they are helpful in

curing other problems, antibiotics may lead to an overgrowth of Candida in the vagina.

Pregnancy: Hormonal changes in the body during pregnancy encourage the growth of yeast. This is

a very common time for an infection to occur. Until the baby is born, it may be hard to completely

eliminate yeast infections. If you believe you are pregnant, tell your doctor.

Menstruation: Sometimes monthly changes in hormone levels may lead to yeast infections.

Diabetes: In addition to heat and moisture, yeast thrives on sugar. Because diabetics often have

sugar in their urine, their vaginas are rich in this substance. Careful control of diabetes may help

prevent yeast infection.

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 or latex condom. Therefore, use of the diaphragm or latex condom

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.

Manufactured by:

G&W Laboratories, Inc.

South Plainfield, NJ 07080

Issued 03/2015

8-0552GW1

PRINCIPAL DISPLAY PANEL - 80 mg Suppository Blister Pack Carton

G&W

Terconazole

Vaginal

Suppos itories

80 mg

NDC 0713-0552-73

Rx only

3 SUPPOSITORIES

WITH VAGINAL APPLICATOR

3

Vaginal

Suppos itories

Keep this and all medications out of the reach of children.

®

TERCONAZOLE

terconazole suppository

Product Information

Product T ype

HUMAN PRESCRIPTION DRUG

Ite m Code (Source )

NDC:0 713-0 552

Route of Administration

VAGINAL

G & W Laboratories, Inc.

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

Terco na zo le (UNII: 0 KJ2VE6 6 4U) (Terco nazo le - UNII:0 KJ2VE6 6 4U)

Te rc o na z o le

8 0 mg

Inactive Ingredients

Ingredient Name

Stre ng th

co co nut o il (UNII: Q9 L0 O73W7L)

pa lm kernel o il (UNII: B0 S9 0 M0 233)

butyla ted hydro xya niso le (UNII: REK49 6 0 K2U)

Product Characteristics

Color

WHITE (white to o ff-white)

S core

S hap e

BULLET (elliptically-shaped)

S iz e

Flavor

Imprint Code

Contains

Packag ing

#

Item Code

Package Description

Marketing Start Date

Marketing End Date

1

NDC:0 713-0 552-73

3 in 1 CARTON

1

1 in 1 BLISTER PACK; Type 0 : No t a Co mbinatio n Pro duct

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

ANDA

ANDA0 77553

0 9 /25/20 15

Labeler -

G & W Laboratories, Inc. (001271188)

Registrant -

T aro Pharmaceuticals U.S.A., Inc. (145186370)

Establishment

Name

Ad d re s s

ID/FEI

Busine ss Ope rations

G & W Labo rato ries, Inc.

0 0 127118 8

MANUFACTURE(0 713-0 552)

Revised: 9/2015