DOSAGE & ADMINISTRATION SECTION.

dosageand administration. Terconazole Vaginal Cream 0.4%:One full applicator (5 g) of Terconazole Vaginal Cream (20mg terconazole) should be administered intravaginally once daily at bedtimefor seven consecutive days.. Terconazole Vaginal Cream 0.8%:One full applicator (5 g) of Terconazole Vaginal Cream (40mg terconazole) should be administered intravaginally once daily at bedtimefor three consecutive days.Before prescribinganother course of therapy, the diagnosis should be reconfirmed by smears and/orcultures and other pathogens commonly associated with vulvovaginitis ruledout. The therapeutic effect of these products is not affected by menstruation.

DRUG INTERACTIONS SECTION.

DrugInteractions:. TerconazoleVaginal Cream 0.4%:The therapeutic effect of this productis not affected by oral contraceptive usage.. Terconazole Vaginal Cream 0.8%:Thelevels of estradiol (E2) and progesterone did not differ significantly when0.8% terconazole vaginal cream was administered to healthy female volunteersestablished on low dose oral contraceptive.

GENERAL PRECAUTIONS SECTION.

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

GERIATRIC USE SECTION.

GeriatricUse:. Clinical studies of terconazoledid not include sufficient numbers of subjects aged 65 and over to determinewhether they respond differently from younger subjects. Other reported clinicalexperience has not identified differences in responses between the elderlyand younger patients.

HOW SUPPLIED SECTION.

how supplied. Terconazole Vaginal Cream 0.4% is available in 45 (NDC 0591-3196-89)tubes with measured-dose applicator. Store at Controlled Room Temperature15 30 (59 86 F).TerconazoleVaginal Cream 0.8% is available in 20 (NDC 0591-3197-52) tubes with measured-doseapplicator. Store at Controlled Room Temperature 15 30 (59- 86 F).

INDICATIONS & USAGE SECTION.

indications and usage. Terconazole Vaginal Cream is indicated for the local treatmentof vulvovaginal candidiasis (moniliasis). As this product is effective onlyfor vulvovaginitis caused by the genus Candida, the diagnosis should be confirmedby KOH smears and/or cultures.

MICROBIOLOGY SECTION.

Microbiology:. Terconazole exhibits fungicidal activity in vitro against Candidaalbicans. Antifungal activity has also been demonstrated againstother fungi. The MIC values of terconazole against most Lactobacillus spp.typically found in the human vagina were >=128 mcg/mL; therefore thesebeneficial bacteria were 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 normalfungal cell membrane permeability. No resistance to terconazole has developedduring successive passages of C. albicans.

NURSING MOTHERS SECTION.

NursingMothers:. It is not known whetherthis drug is excreted in human milk. Animal studies have shown that rat offspringexposed via the milk of treated (40 mg/kg/orally) dams showed decreased survivalduring the first few post-partum days, but overall pup weight and weight gainwere comparable to or greater than controls throughout lactation. Becausemany drugs are excreted in human milk, and because of the potential for adversereaction in nursing infants from terconazole, decision should be made whetherto discontinue nursing or to discontinue the drug, taking into account theimportance of the drug to the mother.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.

PRINCIPAL DISPLAY PANEL. NDC 55045-3259-03 PRINCIPAL DISPLAY PANEL Terconazole Vaginal Cream0.8%Tube and ApplicatorFor Vaginal Use Only.Rx onlyNet Wt 0.71 oz. (20 g)Quantity by weight not by volume.. NDC 55045-3259-03.

PEDIATRIC USE SECTION.

PediatricUse:. Safety and efficacy inchildren have not been established.

PRECAUTIONS SECTION.

precautions. General:. Discontinue use and do not retreat with terconazole if sensitization,irritation, fever, chills or flu-like symptoms are reported during use.. LaboratoryTests:. If there is lack ofresponse to terconazole, appropriate microbiologic studies (standard KOH smearand/or cultures) should be repeated to confirm the diagnosis and rule outother pathogens.. DrugInteractions:. TerconazoleVaginal Cream 0.4%:The therapeutic effect of this productis not affected by oral contraceptive usage.. Terconazole Vaginal Cream 0.8%:Thelevels of estradiol (E2) and progesterone did not differ significantly when0.8% terconazole vaginal cream was administered to healthy female volunteersestablished on low dose oral contraceptive.. Carcinogenesis,Mutagenesis, Impairment of Fertility:. Carcinogenesis:Studies to determinethe carcinogenic potential of terconazole have not been performed.. Mutagenicity:Terconazole was notmutagenic when tested in vitro for induction of microbialpoint mutations (Ames test), or for inducing cellular transformation, or invivo for chromosome breaks (micronucleus test) or dominant lethalmutations in mouse germ cells.. Impairment of Fertility:Noimpairment of fertility occurred when female rats were administered terconazoleorally up to 40 mg/kg/day for three month period.. Pregnancy:Teratogenic Effects:. TeratogenicEffects. Pregnancy Category C.There was no evidence of teratogenicity when terconazole wasadministered orally up to 40 mg/kg/day (50x the recommended intravaginal humandose of the 0.8% vaginal cream formulation, and 100x the intravaginal humandose 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.Dosagesat or below 10 mg/kg/day produced no embryotoxicity; however, there was adelay in fetal ossification at 10 mg/kg/day in rats. There was some evidenceof embryotoxicity in rabbits and rats at 20-40 mg/kg. In rats, this was reflectedas decrease in litter size and number of viable young and reduced fetalweight. There was also delay in ossification and an increased incidence ofskeletal variants.The no-effect doseof 10 mg/kg/day resulted in mean peak plasma level of terconazole in pregnantrats 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 ofterconazole 0.4% vaginal cream, and by 30 times the mean peak plasma level(0.006 mcg/mL) seen in normal subjects after intravaginal administration ofterconazole 0.8% vaginal cream. This safety assessment does not account forpossible exposure of the fetus through direct transfer to terconazole fromthe irritated vagina by diffusion across amniotic membranes.Since terconazole is absorbed from the human vagina, it shouldnot be used in the first trimester of pregnancy unless the physician considersit essential to the welfare of the patient.. NursingMothers:. It is not known whetherthis drug is excreted in human milk. Animal studies have shown that rat offspringexposed via the milk of treated (40 mg/kg/orally) dams showed decreased survivalduring the first few post-partum days, but overall pup weight and weight gainwere comparable to or greater than controls throughout lactation. Becausemany drugs are excreted in human milk, and because of the potential for adversereaction in nursing infants from terconazole, decision should be made whetherto discontinue nursing or to discontinue the drug, taking into account theimportance of the drug to the mother.. PediatricUse:. Safety and efficacy inchildren have not been established.. GeriatricUse:. Clinical studies of terconazoledid not include sufficient numbers of subjects aged 65 and over to determinewhether they respond differently from younger subjects. Other reported clinicalexperience has not identified differences in responses between the elderlyand younger patients.

ADVERSE REACTIONS SECTION.

adverse reactions. Terconazole Vaginal Cream 0.4%:During controlled clinical studies conducted in the UnitedStates, 521 patients with vulvovaginal candidiasis were treated with terconazole0.4% vaginal cream. Based on comparative analyses with placebo, the adverseexperiences considered most likely related to terconazole 0.4% vaginal creamwere 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%) occurredless frequently with terconazole 0.4% vaginal cream than with the vehicleplacebo. Fever (1.7% vs. 0.5% with placebo) and chills (0.4% vs. 0.0% withplacebo) have also been reported. The therapy-related dropout rate was 1.9%.The adverse drug experience on terconazole most frequently causing discontinuationwas vulvovaginal itching (0.6%), which was lower than the incidence for placebo(0.9%).. Terconazole Vaginal Cream0.8%:During controlledclinical studies conducted in the United States, patients with vulvovaginalcandidiasis were treated with terconazole 0.8% vaginal cream for three days.Based on comparative analyses with placebo and standard agent, the adverseexperiences considered most likely related to terconazole 0.8% vaginal creamwere headache (21% vs. 16% with placebo) and dysmenorrhea (6% vs. 2% withplacebo). Genital complaints in general, and burning and itching in particular,occurred less frequently in the terconazole 0.8% vaginal cream day regimen(5% vs. 6%-9% with placebo). Other adverse experiences reported withterconazole 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 was2.0% for the terconazole 0.8% vaginal cream. The adverse drug experience mostfrequently causing discontinuation of therapy was vulvovaginal itching, 0.7%with the terconazole 0.8% vaginal cream group and 0.3% with the placebo group.

CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION.

Carcinogenesis:Studies to determinethe carcinogenic potential of terconazole have not been performed.

CLINICAL PHARMACOLOGY SECTION.

clinicalpharmacology. Following intravaginaladministration of terconazole in humans, absorption ranged from 5-8%in three hysterectomized subjects and 12-16% in two non-hysterectomizedsubjects with tubal ligations.Followingdaily intravaginal administration of 0.8% terconazole 40 mg (0.8% cream x5 g) for seven days to normal humans, plasma concentrations were low and graduallyrose to daily peak (mean of 5.9 ng/mL or 0.006 mcg/mL) at 6.6 hours.Results from similar studies in patients with vulvovaginalcandidiasis indicate that the slow rate of absorption, the lack of accumulation,and the mean peak plasma concentration of terconazole was not different fromthat observed in healthy women. The absorption characteristics of terconazole0.8% in pregnant or non-pregnant patients with vulvovaginal candidiasis werealso similar to those found in normal volunteers.Followingoral (30 mg) administration of 14C-labelled terconazole,the harmonic half-life of elimination from the blood for the parent terconazolewas 6.9 hours (range 4.0-11.3). Terconazole is extensively metabolized;the plasma AUC for terconazole compared to the AUC for total radioactivitywas 0.6%. Total radioactivity was eliminated from the blood with harmonichalf-life of 52.2 hours (range 44-60). Excretion of radioactivity wasboth 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 volunteersfollowing repeated dermal application of terconazole 2.0% and 0.8% creamsunder conditions of filtered artificial ultraviolet light.Photosensitivity reactions have not been observed in U.S. andforeign clinical trials in patients who were treated with terconazole suppositoriesor vaginal cream (0.4% and 0.8%).. Microbiology:. Terconazole exhibits fungicidal activity in vitro against Candidaalbicans. Antifungal activity has also been demonstrated againstother fungi. The MIC values of terconazole against most Lactobacillus spp.typically found in the human vagina were >=128 mcg/mL; therefore thesebeneficial bacteria were 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 normalfungal cell membrane permeability. No resistance to terconazole has developedduring successive passages of C. albicans.

CONTRAINDICATIONS SECTION.

contraindications. Patients known to be hypersensitive to terconazole or to anyof the components of the cream.

DESCRIPTION SECTION.

description. Terconazole Vaginal Cream 0.4% is white to off-white, waterwashable cream for intravaginal administration containing 0.4% of the antifungalagent 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 cream base consisting of butylated hydroxyanisole, cetyl alcohol,isopropyl myristate, polysorbate 60, polysorbate 80, propylene glycol, stearylalcohol, and purified water.TerconazoleVaginal Cream 0.8% is white to off-white, water washable cream for intravaginaladministration 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 cream base consisting of butylated hydroxyanisole, cetyl alcohol,isopropyl myristate, polysorbate 60, polysorbate 80, propylene glycol, stearylalcohol, and purified water.The structuralformula of terconazole is as follows:Terconazole, triazole derivative, is awhite to almost white powder with molecular weight of 532.47.It is insoluble in water; sparingly soluble in ethanol; and soluble in butanol.. Chemical Structure for Terconazole.

PREGNANCY SECTION.

Pregnancy:Teratogenic Effects:. TeratogenicEffects. Pregnancy Category C.There was no evidence of teratogenicity when terconazole wasadministered orally up to 40 mg/kg/day (50x the recommended intravaginal humandose of the 0.8% vaginal cream formulation, and 100x the intravaginal humandose 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.Dosagesat or below 10 mg/kg/day produced no embryotoxicity; however, there was adelay in fetal ossification at 10 mg/kg/day in rats. There was some evidenceof embryotoxicity in rabbits and rats at 20-40 mg/kg. In rats, this was reflectedas decrease in litter size and number of viable young and reduced fetalweight. There was also delay in ossification and an increased incidence ofskeletal variants.The no-effect doseof 10 mg/kg/day resulted in mean peak plasma level of terconazole in pregnantrats 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 ofterconazole 0.4% vaginal cream, and by 30 times the mean peak plasma level(0.006 mcg/mL) seen in normal subjects after intravaginal administration ofterconazole 0.8% vaginal cream. This safety assessment does not account forpossible exposure of the fetus through direct transfer to terconazole fromthe irritated vagina by diffusion across amniotic membranes.Since terconazole is absorbed from the human vagina, it shouldnot be used in the first trimester of pregnancy unless the physician considersit essential to the welfare of the patient.

SPL PATIENT PACKAGE INSERT SECTION.

TERCONAZOLE Vaginal Cream 0.4%7-Day Regimen TERCONAZOLE Vaginal Cream 0.8%3-Day RegimenPATIENT INSTRUCTIONSFilling 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.Using the Applicator: 1.Lie on your back with your knees drawn up toward your chest.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: 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.NOTE: Store the cream at Controlled Room Temperature 15-30C (59-86F). See end flap for lot number and expiration date.A WORD ABOUT YEAST INFECTIONSWhy Do Yeast Infections OccurYeast 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 yeast infection. Symptoms of yeast infection include itching, burning, redness, and an abnormal discharge.Your doctor can make the diagnosis of yeast infection by evaluating your symptoms and looking at sample of the discharge under the microscope.How Can Prevent Yeast InfectionsCertain factors may increase your chance of developing yeast infection. These factors dont actually cause the problem, but they may create 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 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. 3.If your partner has any penile itching, redness, or discomfort, he should consult his physician and mention that you are being treated for 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 sanitary napkin if the vaginal medication leaks.5.Dry the genital area thoroughly after showering, bathing, or swimming. Change out of wet bathing suit or damp exercise clothes as soon as possible. dry environment is less likely to encourage the growth of yeast.6.Wipe from front to rear (away from the vagina) after bowel movement.7.Dont douche unless your doctor specifically tells you to do so. Douching may disturb the vaginal balance.8.Dont 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.Mfd. for: Watson Laboratories, Inc.Corona, CA 92880 USAMfd. by: Draxis Specialty Pharmaceuticals Inc.Kirkland, Quebec, Canada H9H 4J4 or JOLLCManati, Puerto Rico 00674 Printed in U.S.A.Revised January 2010. 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.. 1.Lie on your back with your knees drawn up toward your chest.. 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.. 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.. 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 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.. 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. 3.If your partner has any penile itching, redness, or discomfort, he should consult his physician and mention that you are being treated for 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 sanitary napkin if the vaginal medication leaks.. 5.Dry the genital area thoroughly after showering, bathing, or swimming. Change out of wet bathing suit or damp exercise clothes as soon as possible. dry environment is less likely to encourage the growth of yeast.. 6.Wipe from front to rear (away from the vagina) after bowel movement.. 7.Dont douche unless your doctor specifically tells you to do so. Douching may disturb the vaginal balance.. 8.Dont 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.. Remove the cap from the tube.. Screw applicator onto the tube.. Insert the fillled applicator into the vagina as far as it will comfortably go.. Pull the plunger out of the barrel.

SPL UNCLASSIFIED SECTION.

LaboratoryTests:. If there is lack ofresponse to terconazole, appropriate microbiologic studies (standard KOH smearand/or cultures) should be repeated to confirm the diagnosis and rule outother pathogens.

TERATOGENIC EFFECTS SECTION.

TeratogenicEffects. Pregnancy Category C.There was no evidence of teratogenicity when terconazole wasadministered orally up to 40 mg/kg/day (50x the recommended intravaginal humandose of the 0.8% vaginal cream formulation, and 100x the intravaginal humandose 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.Dosagesat or below 10 mg/kg/day produced no embryotoxicity; however, there was adelay in fetal ossification at 10 mg/kg/day in rats. There was some evidenceof embryotoxicity in rabbits and rats at 20-40 mg/kg. In rats, this was reflectedas decrease in litter size and number of viable young and reduced fetalweight. There was also delay in ossification and an increased incidence ofskeletal variants.The no-effect doseof 10 mg/kg/day resulted in mean peak plasma level of terconazole in pregnantrats 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 ofterconazole 0.4% vaginal cream, and by 30 times the mean peak plasma level(0.006 mcg/mL) seen in normal subjects after intravaginal administration ofterconazole 0.8% vaginal cream. This safety assessment does not account forpossible exposure of the fetus through direct transfer to terconazole fromthe irritated vagina by diffusion across amniotic membranes.Since terconazole is absorbed from the human vagina, it shouldnot be used in the first trimester of pregnancy unless the physician considersit essential to the welfare of the patient.

WARNINGS SECTION.

warnings. None.