NDC 0023-8335 Tazorac

Tazarotene

NDC Product Code 0023-8335

NDC 0023-8335-03

Package Description: 1 TUBE in 1 CARTON > 30 g in 1 TUBE

NDC 0023-8335-10

Package Description: 1 TUBE in 1 CARTON > 100 g in 1 TUBE

NDC 0023-8335-15

Package Description: 15 TUBE in 1 CARTON > 3.5 g in 1 TUBE

NDC Product Information

Tazorac with NDC 0023-8335 is a a human prescription drug product labeled by Allergan, Inc.. The generic name of Tazorac is tazarotene. The product's dosage form is gel and is administered via cutaneous form.

Labeler Name: Allergan, Inc.

Dosage Form: Gel - A semisolid3 dosage form that contains a gelling agent to provide stiffness to a solution or a colloidal dispersion.4 A gel may contain suspended particles.

Product Type: Human Prescription Drug What kind of product is this?
Indicates the type of product, such as Human Prescription Drug or Human Over the Counter Drug. This data element matches the “Document Type” field of the Structured Product Listing.

Tazorac Active Ingredient(s)

What is the Active Ingredient(s) List?
This is the active ingredient list. Each ingredient name is the preferred term of the UNII code submitted.

  • TAZAROTENE .5 mg/g

Inactive Ingredient(s)

About the Inactive Ingredient(s)
The inactive ingredients are all the component of a medicinal product OTHER than the active ingredient(s). The acronym "UNII" stands for “Unique Ingredient Identifier” and is used to identify each inactive ingredient present in a product.

  • BENZYL ALCOHOL (UNII: LKG8494WBH)
  • ASCORBIC ACID (UNII: PQ6CK8PD0R)
  • BUTYLATED HYDROXYANISOLE (UNII: REK4960K2U)
  • BUTYLATED HYDROXYTOLUENE (UNII: 1P9D0Z171K)
  • CARBOMER HOMOPOLYMER TYPE B (ALLYL PENTAERYTHRITOL CROSSLINKED) (UNII: HHT01ZNK31)
  • EDETATE DISODIUM (UNII: 7FLD91C86K)
  • HEXYLENE GLYCOL (UNII: KEH0A3F75J)
  • POLOXAMER 407 (UNII: TUF2IVW3M2)
  • POLYETHYLENE GLYCOL 400 (UNII: B697894SGQ)
  • POLYSORBATE 40 (UNII: STI11B5A2X)
  • WATER (UNII: 059QF0KO0R)
  • TROMETHAMINE (UNII: 023C2WHX2V)

Administration Route(s)

What are the Administration Route(s)?
The translation of the route code submitted by the firm, indicating route of administration.

  • Cutaneous - Administration to the skin.

Pharmacological Class(es)

What is a Pharmacological Class?
These are the reported pharmacological class categories corresponding to the SubstanceNames listed above.

  • Retinoid - [EPC] (Established Pharmacologic Class)
  • Retinoids - [CS]

Product Labeler Information

What is the Labeler Name?
Name of Company corresponding to the labeler code segment of the Product NDC.

Labeler Name: Allergan, Inc.
Labeler Code: 0023
FDA Application Number: NDA020600 What is the FDA Application Number?
This corresponds to the NDA, ANDA, or BLA number reported by the labeler for products which have the corresponding Marketing Category designated. If the designated Marketing Category is OTC Monograph Final or OTC Monograph Not Final, then the Application number will be the CFR citation corresponding to the appropriate Monograph (e.g. “part 341”). For unapproved drugs, this field will be null.

Marketing Category: NDA - A product marketed under an approved New Drug Application. What is the Marketing Category?
Product types are broken down into several potential Marketing Categories, such as NDA/ANDA/BLA, OTC Monograph, or Unapproved Drug. One and only one Marketing Category may be chosen for a product, not all marketing categories are available to all product types. Currently, only final marketed product categories are included. The complete list of codes and translations can be found at www.fda.gov/edrls under Structured Product Labeling Resources.

Start Marketing Date: 08-01-1997 What is the Start Marketing Date?
This is the date that the labeler indicates was the start of its marketing of the drug product.

Listing Expiration Date: 12-31-2019 What is the Listing Expiration Date?
This is the date when the listing record will expire if not updated or certified by the product labeler.

Exclude Flag: N What is the NDC Exclude Flag?
This field indicates whether the product has been removed/excluded from the NDC Directory for failure to respond to FDA’s requests for correction to deficient or non-compliant submissions. Values = ‘Y’ or ‘N’.

* Please review the disclaimer below.

Information for Patients

Tazarotene

Tazarotene is pronounced as (taz ar' oh teen)

Why is tazarotene medication prescribed?
Tazarotene (Tazorac, Fabior) is used to treat acne. Tazarotene (Tazorac) is also used to treat psoriasis (a skin disease in which red, scaly patches form on some areas of...
[Read More]

* Please review the disclaimer below.

Tazorac Product Labeling Information

The product labeling information includes all published material associated to a drug. Product labeling documents include information like generic names, active ingredients, ingredient strength dosage, routes of administration, appearance, usage, warnings, inactive ingredients, etc.

Product Labeling Index

1.1 Plaque Psoriasis

TAZORAC® (tazarotene) Gel, 0.05% and 0.1% are indicated for the topical treatment of patients with plaque psoriasis of up to 20% body surface area involvement.

1.2 Acne Vulgaris

TAZORAC (tazarotene) Gel, 0.1% is also indicated for the topical treatment of patients with facial acne vulgaris of mild to moderate severity.The efficacy of TAZORAC Gel in the treatment of acne previously treated with other retinoids or resistant to oral antibiotics has not been established.

1.3 Limitations Of Use

The safety of TAZORAC Gel use on more than 20% body surface area has not been established in psoriasis or acne [see Warnings and Precautions (5.1) and Use in Specific Populations (8.1)].

2  Dosage And Administration

TAZORAC Gel is for topical use only. TAZORAC Gel is not for ophthalmic, oral, or intravaginal use. Avoid accidental transfer of TAZORAC Gel into eyes, mouth, or other mucous membranes. If contact with mucous membranes occurs, rinse thoroughly with water [see Warnings and Precautions (5.2)].Wash hands thoroughly after application.

2.1 Psoriasis

It is recommended that treatment starts with TAZORAC Gel, 0.05%, with strength increased to 0.1% if tolerated and medically indicated. Apply a thin film (2 mg/cm2) of TAZORAC Gel once per day, in the evening, to cover only the psoriatic lesions on no more than 20% of body surface area. If a bath or shower is taken prior to application, the skin should be dry before applying the gel. If emollients are used, they should be applied at least an hour before application of TAZORAC Gel. Because unaffected skin may be more susceptible to irritation, application of tazarotene to these areas should be carefully avoided. TAZORAC Gel was investigated for up to 12 months during clinical trials for psoriasis.

2.2 Acne

Cleanse the face gently. After the skin is dry, apply a thin layer (2 mg/cm2) of TAZORAC Gel 0.1% once per day, in the evening, to the skin where acne lesions appear. Use enough to cover the entire affected area. TAZORAC Gel was investigated for up to 12 weeks during clinical trials for acne.Use effective sunscreens and wear protective clothing while using TAZORAC Gel [see Warnings and Precautions (5.3)].

3  Dosage Forms And Strengths

Gel, 0.05% and 0.1%, in 30 g and 100 g tubes. Each gram of TAZORAC Gel, 0.05% and 0.1% contains 0.5 mg and 1 mg of tazarotene, respectively in a translucent, aqueous gel.

4  Contraindications

  • TAZORAC Gel is contraindicated in: Pregnancy. Retinoids may cause fetal harm when administered to a pregnant female [see Warnings and Precautions (5.1), Use in Specific Populations (8.1, 8.3)].Individuals who have known hypersensitivity to any of its components [see Warnings and Precautions (5.2)].

5.1 Embryofetal Toxicity

Based on data from animal reproduction studies, retinoid pharmacology and the potential for systemic absorption, TAZORAC Gel may cause fetal harm when administered to a pregnant female and is contraindicated during pregnancy. Tazarotene elicits malformations and developmental effects associated with retinoids after topical and oral administration to pregnant rats and rabbits during organogenesis.Systemic exposure to tazarotenic acid is dependent upon the extent of the body surface area treated. In patients treated topically over sufficient body surface area, exposure could be in the same order of magnitude as in orally treated animals.Although there may be less systemic exposure in the treatment of acne of the face alone due to less surface area for application, tazarotene is a teratogenic substance and causes fetal malformations in animals, and it is not known what level of exposure is required for teratogenicity in humans [see Clinical Pharmacology (12.3)].There were thirteen reported pregnancies in subjects who participated in the clinical trials for topical tazarotene. Nine of the subjects had been treated with topical tazarotene, and the other four had been treated with vehicle. One of the subjects who was treated with tazarotene cream  elected to terminate the pregnancy for non-medical reasons unrelated to treatment. The other eight pregnant women who were inadvertently exposed to topical tazarotene during the clinical trials subsequently delivered apparently healthy babies. As the exact timing and extent of exposure in relation to the gestation times are not certain, the significance of these findings is unknown.Females of Child-bearing PotentialFemales of child-bearing potential should be warned of the potential risk and use adequate birth-control measures when TAZORAC Gel is used. The possibility that a female of child-bearing potential is pregnant at the time of institution of therapy should be considered. A negative result for pregnancy test should be obtained within 2 weeks prior to TAZORAC Gel therapy. TAZORAC Gel therapy should begin during a normal menstrual period [see Use in Specific Populations (8.1)].

5.2 Local Irritation And Hypersensitivity Reactions

Application of TAZORAC Gel may cause excessive irritation in the skin of certain sensitive individuals. Local reactions (including blistering and skin desquamation, pruritus, burning, erythema) and hypersensitivity adverse reactions (including urticaria) have been observed with topical tazarotene. If these adverse reactions occur, consider discontinuing the medication or reducing the dosing frequency, as appropriate, until the integrity of the skin is restored.  Alternatively, patients with psoriasis who are being treated with the 0.1% concentration can be switched to the lower concentration. Frequency of application should be closely monitored by careful observation of the clinical therapeutic response and skin tolerance.  Therapy can be resumed, or the drug concentration or frequency of application can be increased as the patient becomes able to tolerate treatment.Concomitant topical medications and cosmetics that have a strong drying effect should be avoided. It is also advisable to "rest" a patient's skin until the effects of such preparations subside before treatment with TAZORAC Gel is initiated.TAZORAC Gel, should not be used on eczematous skin, as it may cause severe irritation.Weather extremes, such as wind or cold, may be more irritating to patients using TAZORAC Gel.

5.3 Photosensitivity And Risk For Sunburn

Because of heightened burning susceptibility, exposure to sunlight (including sunlamps) should be avoided unless deemed medically necessary, and in such cases, exposure should be minimized during the use of TAZORAC Gel. Patients must be warned to use sunscreens and protective clothing when using TAZORAC Gel. Patients with sunburn should be advised not to use TAZORAC Gel until fully recovered. Patients who may have considerable sun exposure due to their occupation and those patients with inherent sensitivity to sunlight should exercise particular caution when using TAZORAC Gel.TAZORAC Gel should be administered with caution if the patient is also taking drugs known to be photosensitizers (e.g., thiazides, tetracyclines, fluoroquinolones, phenothiazines, sulfonamides) because of the increased possibility of augmented photosensitivity.

6  Adverse Reactions

The following serious adverse reactions are discussed in more detail in other sections of the labeling:•
     
Embryofetal toxicity [see Warnings and Precautions (5.1)]•
     
Photosensitivity and Risk of Sunburn [see Warnings and Precautions (5.3)]

6.1 Clinical Trials Experience

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.Psoriasis A total of 439 subjects 14 to 87 years of age were treated with TAZORAC Gel, 0.05% and 0.1% in two controlled clinical trials. The most frequent adverse events reported with TAZORAC Gel, 0.05% and 0.1% occurring in 10 to 30% of subjects, in descending order, included pruritus, burning/stinging, erythema, worsening of psoriasis, irritation, and skin pain. Reactions occurring in 1 to 10% of subjects included rash, desquamation, irritant contact dermatitis, skin inflammation, fissuring, bleeding, and dry skin. Increases in “psoriasis worsening” and “sun-induced erythema” were noted in some subjects over the 4th to 12th months of treatment as compared to the first three months of a 1 year study. In general, the incidence of adverse events with TAZORAC Gel 0.05% was 2 to 5% lower than that seen with TAZORAC Gel 0.1%.Acne A total of 596 subjects 12 to 44 years of age were treated with TAZORAC Gel, 0.05% and 0.1% in two controlled clinical trials. The most frequent adverse events reported during clinical trials with TAZORAC Gel, 0.1% in the treatment of acne occurring in 10 to 30% of subjects, in descending order, included desquamation, burning/stinging, dry skin, erythema and pruritus. Reactions occurring in 1 to 10% of subjects included irritation, skin pain, fissuring, localized edema and skin discoloration.

6.2 Postmarketing Experience

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. The following adverse reactions have been identified during postapproval use of tazarotene.Skin and subcutaneous tissue disorders: blister, dermatitis, urticaria, skin exfoliation, skin discoloration (including skin hyperpigmentation or skin hypopigmentation), swelling at or near application sites, and pain.

7  Drug Interactions

No formal drug-drug interaction studies were conducted with TAZORAC Gel.In a trial of 27 healthy female subjects between the ages of 20–55 years receiving a combination oral contraceptive tablet containing 1 mg norethindrone and 35 mcg ethinyl estradiol, concomitant use of tazarotene administered as 1.1 mg orally (mean ± SD Cmax and AUC0-24 of tazarotenic acid were 28.9 ± 9.4 ng/mL and 120.6 ± 28.5 ng•hr/mL, respectively) did not affect the pharmacokinetics of norethindrone and ethinyl estradiol over a complete cycle.The impact of tazarotene on the pharmacokinetics of progestin only oral contraceptives (i.e., minipills) has not been evaluated.

8.1 Pregnancy

Risk SummaryBased on data from animal reproduction studies, retinoid pharmacology, and the potential for systemic absorption, TAZORAC Gel may cause fetal harm when administered to a pregnant female and is contraindicated during pregnancy. Safety in pregnant females has not been established. The potential risk to the fetus outweighs the potential benefit to the mother from TAZORAC Gel during pregnancy; therefore, TAZORAC Gel should be discontinued as soon as pregnancy is recognized [see Contraindications (4), Warnings and Precautions (5.1), Clinical Pharmacology (12.3)]. Limited case reports of pregnancy in females enrolled in clinical trials for TAZORAC Gel have not established a clear association with tazarotene and major birth defects or miscarriage risk. Because the exact timing and extent of exposure in relation to the gestational age are not certain, the significance of these findings is unknown.In animal reproduction studies with pregnant rats, tazarotene dosed topically during organogenesis at 0.5 times the maximum systemic exposure in subjects treated with the maximum recommended human dose (MRHD) of tazarotene gel, 0.1% resulted in reduced fetal body weights and reduced skeletal ossification. In animal reproduction studies with pregnant rabbits dosed topically with tazarotene gel at 7 times the maximum systemic exposure in subjects treated with the MRHD of tazarotene gel, 0.1%, there were single incidences of known retinoid malformations, including spina bifida, hydrocephaly, and heart anomalies.In animal reproduction studies with pregnant rats and rabbits, tazarotene dosed orally during organogenesis at 0.5 and 13 times, respectively, the maximum systemic exposure in subjects treated with the MRHD of tazarotene gel, 0.1% resulted in malformations, fetal toxicity, developmental delays, and/or behavioral delays. In pregnant rats, tazarotene dosed orally prior to mating through early gestation resulted in decreased litter size, decreased numbers of live fetuses, decreased fetal body weights, and increased malformations at doses approximately 2 times higher than the maximum systemic exposure in subjects treated with the MRHD of tazarotene gel, 0.1% [see Data].The background risk of major birth defects and miscarriage for the indicated population is unknown. Adverse outcomes in pregnancy occur regardless of the health of the mother or the use of medications. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.DataAnimal DataIn rats, a tazarotene gel, 0.05% formulation dosed topically during gestation days 6 through 17 at 0.25 mg/kg/day, which represented 0.5 times the maximum systemic exposure in subjects treated with the MRHD of tazarotene gel, 0.1% (i.e., 2 mg/cm2 over a 20% body surface area), resulted in reduced fetal body weights and reduced skeletal ossification. Rabbits dosed topically with 0.25 mg/kg/day tazarotene gel, which represented 7 times the maximum systemic exposure in subjects treated with the MRHD of tazarotene gel, 0.1%, during gestation days 6 through 18 were noted with single incidences of known retinoid malformations, including spina bifida, hydrocephaly, and heart anomalies.When tazarotene was given orally to animals, developmental delays were seen in rats, and malformations and post-implantation loss were observed in rats and rabbits at doses producing 0.5 and 13 times, respectively, the maximum systemic exposure in subjects treated with the MRHD of tazarotene gel, 0.1%.In female rats orally administered 2 mg/kg/day of tazarotene from 15 days before mating through gestation day 7, which represented 2 times the maximum systemic exposure in subjects treated with the MRHD of tazarotene gel, 0.1%, classic developmental effects of retinoids were observed including decreased number of implantation sites, decreased litter size, decreased numbers of live fetuses, and decreased fetal body weights. A low incidence of retinoid-related malformations was observed at that dose. In a pre- and postnatal development toxicity study, topical administration of tazarotene gel (0.125 mg/kg/day) to pregnant female rats from gestation day 16 through lactation day 20 reduced pup survival, but did not affect the reproductive capacity of the offspring. Based on data from another study, the maximum systemic exposure in the rat would be 0.3 times the maximum systemic exposure in subjects treated with the MRHD of tazarotene gel, 0.1%.

8.2 Lactation

Risk SummaryThere is no information regarding the presence of tazarotene in human milk, the effects on the breastfed infant, or the effects on milk production. After single topical doses of 14C-tazarotene gel to the skin of lactating rats, radioactivity was detected in rat milk. The lack of clinical data during lactation precludes a clear determination of the risk of TAZORAC Gel to an infant during lactation; therefore, the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for TAZORAC Gel and any potential adverse effects on the breastfed child from TAZORAC Gel or from the underlying maternal condition.

8.3 Females And Males Of Reproductive Potential

Pregnancy TestingPregnancy testing is recommended for females of reproductive potential within 2 weeks prior to initiating TAZORAC Gel therapy which should begin during a menstrual period.ContraceptionFemalesBased on animal studies, TAZORAC Gel may cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)]. Advise females of reproductive potential to use effective contraception during treatment with TAZORAC Gel.

8.4 Pediatric Use

The safety and efficacy of TAZORAC Gel have not been established in pediatric patients with psoriasis or acne under the age of 12 years.

8.5 Geriatric Use

Of the total number of subjects in clinical trials of TAZORAC Gel for plaque psoriasis, 163 were over the age of 65. Subjects over 65 years of age experienced more adverse events and lower treatment success rates after 12 weeks of use of TAZORAC Gel compared with those 65 years of age and younger. Currently there is no other clinical experience on the differences in responses between the elderly and younger subjects, but greater sensitivity of some older individuals cannot be ruled out. Tazarotene gel for the treatment of acne has not been clinically evaluated in persons over the age of 65.

10  Overdosage

Excessive topical use of TAZORAC Gel, 0.05% and 0.1% may lead to marked redness, peeling, or discomfort [see Warnings and Precautions (5.2)].TAZORAC Gel 0.05% and 0.1% are not for oral use. Oral ingestion of the drug may lead to the same adverse effects as those associated with excessive oral intake of Vitamin A (hypervitaminosis A) or other retinoids. If oral ingestion occurs, the patient should be monitored, and appropriate supportive measures should be administered as necessary.

11  Description

TAZORAC (tazarotene) Gel, 0.05% and 0.1% is for topical use and contains the active ingredient, tazarotene. Each gram of TAZORAC Gel, 0.05% and 0.1% contains 0.5 and 1 mg of tazarotene, respectively in a translucent, aqueous gel. Tazarotene is a member of the acetylenic class of retinoids. Chemically, tazarotene is ethyl 6-[(4,4-dimethylthiochroman-6-yl)ethynyl]nicotinate. The compound has an empirical formula of C21H21NO2S and molecular weight of 351.46. The structural formula is shown below:TAZORAC Gel contains the following inactive ingredients:benzyl alcohol 1%;ascorbic acid; butylated hydroxyanisole; butylated hydroxytoluene; carbomer homopolymer type B; edetate disodium; hexylene glycol; poloxamer 407; polyethylene glycol 400; polysorbate 40; purified water; and tromethamine.

12.1 Mechanism Of Action

Tazarotene is a retinoid prodrug which is converted to its active form, the carboxylic acid of tazarotene, by deesterification. Tazarotenic acid binds to all three members of the retinoic acid receptor (RAR) family: RARα, RARβ, and RARγ, but shows relative selectivity for RARβ, and RARγ and may modify gene expression. The clinical significance of these findings for the treatment of plaque psoriasis and facial acne vulgaris is unknown.

12.2 Pharmacodynamics

The pharmacodynamics of TAZORAC Gel in the treatment of plaque psoriasis and facial acne vulgaris are unknown.

12.3 Pharmacokinetics

Following topical application, tazarotene undergoes esterase hydrolysis to form its active metabolite, tazarotenic acid. Little parent compound could be detected in the plasma. Tazarotenic acid was highly bound to plasma proteins (greater than 99%). Tazarotene and tazarotenic acid were metabolized to sulfoxides, sulfones and other polar metabolites which were eliminated through urinary and fecal pathways. The half-life of tazarotenic acid was approximately 18 hours, following topical application of tazarotene to normal, acne or psoriatic skin.The human in vivo studies described below were conducted with tazarotene gel applied topically at approximately 2 mg/cm2 and left on the skin for 10 to 12 hours. Both the peak plasma concentration (Cmax) and area under the plasma concentration time curve (AUC) refer to the active metabolite only.Two single, topical dose studies were conducted using 14C-tazarotene gel. Systemic absorption, as determined from radioactivity in the excreta, was less than 1% of the applied dose (without occlusion) in six subjects with psoriasis and approximately 5% of the applied dose (under occlusion) in six healthy subjects. One non-radiolabeled single-dose study comparing the 0.05% gel to the 0.1% gel in healthy subjects indicated that the Cmax and AUC were 40% higher for the 0.1% gel.After 7 days of topical dosing with measured doses of tazarotene 0.1% gel on 20% of the total body surface without occlusion in 24 healthy subjects, the Cmax for tazarotenic acid was 0.72 ± 0.58 ng/mL (mean ± SD) occurring 9 hours after the last dose, and the AUC0-24hr for tazarotenic acid was 10.1 ± 7.2 ng·hr/mL. Systemic absorption was 0.91 ± 0.67% of the applied dose.In a 14-day study in five subjects with psoriasis, measured doses of tazarotene 0.1% gel were applied daily by nursing staff to involved skin without occlusion (8 to 18% of total body surface area; mean ± SD: 13 ± 5%). The Cmax for tazarotenic acid was 12.0 ± 7.6 ng/mL occurring 6 hours after the final dose, and the AUC0-24hr for tazarotenic acid was 105 ± 55 ng·hr/mL. Systemic absorption was 14.8 ± 7.6% of the applied dose. Extrapolation of these results to represent dosing on 20% of total body surface yielded estimates for tazarotenic acid with Cmax of 18.9 ± 10.6 ng/mL and AUC0-24hr of 172 ± 88 ng·hr/mL.An in vitro percutaneous absorption study, using radiolabeled drug and freshly excised human skin or human cadaver skin, indicated that approximately 4 to 5% of the applied dose was in the stratum corneum (tazarotene: tazarotenic acid = 5:1) and 2 to 4% was in the viable epidermis-dermis layer (tazarotene: tazarotenic acid = 2:1) 24 hours after topical application of the gel.

13.1 Carcinogenesis, Mutagenesis, Impairment Of Fertility

A long-term study of tazarotene following oral administration of 0.025, 0.050, and 0.125 mg/kg/day to rats showed no indications of increased carcinogenic risks. Based on pharmacokinetic data from a shorter-term study in rats, the highest dose of 0.125 mg/kg/day was anticipated to give systemic exposure in the rat 0.3 times that seen in subjects treated with the MRHD of tazarotene gel, 0.1%.A long-term study with topical administration of up to 0.1% tazarotene in a gel formulation in mice terminated at 88 weeks showed that dose levels of 0.05, 0.125, 0.25, and 1 mg/kg/day (reduced to 0.5 mg/kg/day for males after 41 weeks due to severe dermal irritation) revealed no apparent carcinogenic effects when compared to vehicle control animals. Systemic exposure at the highest dose was 2 times that seen in subjects treated with the MRHD of tazarotene gel, 0.1%.Tazarotene was non-mutagenic in the Ames assay and did not produce structural chromosomal aberrations in a human lymphocyte assay. Tazarotene was non-mutagenic in the CHO/HGPRT mammalian cell forward gene mutation assay and was non-clastogenic in the in vivo mouse micronucleus test.No impairment of fertility occurred in rats when male animals were treated for 70 days prior to mating and female animals were treated for 14 days prior to mating and continuing through gestation and lactation with topical doses of tazarotene gel up to 0.125 mg/kg/day. Based on data from another study, the systemic drug exposure in the rat at the highest dose was 0.3 times that observed in subjects treated with the MRHD of tazarotene gel, 0.1%.    No impairment of mating performance or fertility was observed in male rats treated for 70 days prior to mating with oral doses of up to 1 mg/kg/day tazarotene, which produced systemic exposure that was approximately equivalent to that observed in subjects treated with the MRHD of tazarotene gel, 0.1%. No impairment of mating performance or fertility was observed in female rats treated for 15 days prior to mating and continuing through gestation day 7 with oral doses of tazarotene up to 2 mg/kg/day. However, there was a significant decrease in the number of estrous stages and an increase in developmental effects at that dose, which produced systemic exposure 2 times that observed in subjects treated with the MRHD of tazarotene gel, 0.1% [see Use in Specific Populations (8.1)].

14  Clinical Studies

Psoriasis: In two large vehicle-controlled clinical trials, TAZORAC Gel, 0.05% and 0.1% applied once daily for 12 weeks was significantly more effective than vehicle in reducing the severity of the clinical signs of plaque psoriasis covering up to 20% of body surface area. In one of the studies, subjects were followed up for an additional 12 weeks following cessation of therapy with TAZORAC Gel. Mean baseline scores and changes from baseline (reductions) after treatment in these two trials are shown in Table 1.Table 1. Plaque Elevation, Scaling, and Erythema in Two Controlled Clinical Trials for PsoriasisTAZORAC® 0.05% GelTAZORAC® 0.1% GelVehicle GelTrunk/Arm/LegLesionsKnee/ElbowLesionsTrunk/Arm/LegLesionsKnee/ElbowLesionsTrunk/Arm/LegLesionsKnee/ElbowLesionsN=108N=111N=108N=111N=108N=112N=108N=112N=108N=113N=108N=113PlaqueElevationB*C-12*C-24*2.5-1.4-1.22.6-1.32.6-1.3-1.12.6-1.12.5-1.4-1.12.6-1.42.6-1.5-1.02.6-1.32.4-0.8-0.92.6-0.72.6-0.7-0.72.6-0.6ScalingB*C-12*C-24*2.4-1.1-0.92.5-1.12.5-1.1-0.82.6-0.92.4-1.3-1.02.6-1.32.5-1.2-0.82.7-1.22.4-0.7-0.82.6-0.72.5-0.6-0.72.7-0.6ErythemaB*C-12*C-24*2.4-1.0-1.12.7-0.82.2-0.9-0.72.5-0.82.4-1.0-0.92.8-1.12.3-1.0-0.82.5-0.82.3-0.6-0.72.7-0.52.2-0.5-0.62.5-0.5Plaque elevation, scaling, and erythema scored on a 0-4 scale with 0=none, 1=mild, 2=moderate, 3=severe and 4=very severe.B*=Mean Baseline Severity: C-12*=Mean Change from Baseline at end of 12 weeks of therapy:C-24*=Mean Change from Baseline at week 24 (12 weeks after the end of therapy).Global improvement over baseline at the end of 12 weeks of treatment in these two trials is shown in Table 2.Table 2. Global Improvement over Baseline after Twelve Weeks of Treatment in Two Controlled Clinical Trials for PsoriasisTAZORAC® 0.05% GelTAZORAC® 0.1% GelVehicle GelN=81N=93N=79N=69N=84N=91100% improvement2 (2%)1 (1%)001 (1%)075% improvement23 (28%)17 (18%)30 (38%)17 (25%)10 (12%)9 (10%)50% improvement42 (52%)39 (42%)51 (65%)36 (52%)28 (33%)21 (23%)1-49% improvement21 (26%)32 (34%)18 (23%)23 (33%)27 (32%)32 (35%)No change or worse18 (22%)22 (24%)10 (13%)10 (14%)29 (35%)38 (42%)The 0.1% gel was more effective than the 0.05% gel, but the 0.05% gel was associated with less local irritation than the 0.1% gel [see Adverse Reactions (6.1)].Acne: In two large vehicle-controlled trials, TAZORAC Gel, 0.1% applied once daily was significantly more effective than vehicle in the treatment of facial acne vulgaris of mild to moderate severity. Percent reductions in lesion counts after treatment for 12 weeks in these two trials are shown in Table 3.Table 3. Reduction in Lesion Counts after Twelve Weeks of Treatment in Two Controlled Clinical Trials for AcneTAZORAC® 0.1% GelVehicle GelN=150N=149N=148N=149Noninflammatory lesions55%43%35%27%Inflammatory lesions42%47%30%28%Total lesions52%45%33%27%Global improvement over baseline at the end of 12 weeks of treatment in these two trials is shown in Table 4.Table 4. Global Improvement over Baseline after Twelve Weeks of Treatment in Two Controlled Clinical Trials for AcneTAZORAC® 0.1% GelVehicle GelN=105N=117N=117N=110100% improvement1 (1%)00075% improvement40 (38%)21 (18%)23 (20%)11 (10%)50% improvement71 (68%)56 (48%)47 (40%)32 (29%)1-49% improvement23 (22%)49 (42%)48 (41%)46 (42%)No change or worse11 (10%)12 (10%)22 (19%)32 (29%)

16 How Supplied/Storage And Handling

TAZORAC (tazarotene) Gel is a translucent, aqueous gel, available in concentrations of 0.05% and 0.1%. It is available in a collapsible aluminum tube with a tamper-evident aluminum membrane over the opening and a white propylene screw cap, in 30 g and 100 g sizes.TAZORAC Gel 0.05% 
     
30 g
     
NDC 0023-8335-03TAZORAC Gel 0.05%
     
100 g
     
NDC 0023-8335-10 TAZORAC Gel 0.1%
     
30 g
     
NDC 0023-0042-03 TAZORAC Gel 0.1%
     
100 g
     
NDC 0023-0042-10Storage: Store at 20ºC to 25ºC (68ºF to 77ºF). Excursions permitted from 15ºC to 30ºC (59ºF to 86ºF).

17  Patient Counseling Information

Advise the patient to read the FDA-approved patient labeling (Patient Information).Embryofetal ToxicityInform females of reproductive potential of the potential risk to a fetus. Advise these patients to use effective contraception during treatment with TAZORAC Gel. Advise patients to inform their healthcare provider of a known or suspected pregnancy [see Warnings and Precautions (5.1) and Use in Specific Populations (8.1, 8.3)].Photosensitivity and Risk of SunburnAdvise patients to avoid excessive sun exposure and to use of sunscreens and protective measures (hat, visor). Advise patients to avoid using TAZORAC Gel if also taking other medicines may increase sensitivity to sunlight. Important Administration InstructionsAdvise the patient of the following: 1. For the patient with psoriasis, apply TAZORAC Gel only to psoriasis skin lesions, avoiding uninvolved skin.2. If undue irritation (redness, peeling, or discomfort) occurs, reduce frequency of application or temporarily interrupt treatment. Treatment may be resumed once irritation subsides [see Dosage and Adminstration (2.1)].3. Moisturizers may be used as frequently as desired. 4. Patients with psoriasis may use a cream or lotion to soften or moisten skin at least 1 hour before applying TAZORAC Gel.5. Avoid contact with the eyes. If TAZORAC Gel gets in or near eyes, rinse thoroughly with water. Seek medical attention if eye irritation continues.6. TAZORAC Gel is for topical use only. Do not apply to eyes, mouth, or other mucous membrane. Not for ophthalmic, oral, or intravaginal use.7. Wash hands thoroughly after applying TAZORAC Gel.Revised: 04/2018Distributed by: Allergan USA, Inc.Madison, NJ 07940© 2018 Allergan. All rights reserved.All trademarks are the property of their respective owners.71722US17Pharmacist: Please cut or tear at dotted line and provide this patient package insert to your customer.

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