Professional Information
Tazarotene (Topical)
VA CLASSIFICATION
Primary: DE802
Secondary: DE752
Commonly used brand name(s): Tazorac.
Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).
Category:
Antiacne agent (topical)—
antipsoriatic (topical)—
Indications
Accepted
Acne vulgaris (treatment)—Tazarotene, as the 0.1% gel, is indicated in the treatment of mild to moderate facial acne vulgaris. It is not known if tazarotene is effective in treatment of acne vulgaris resistant to antibiotics or for acne treated previously with other retinoid medications {01}.
—One study of patients treated with tazarotene or with a vehicle gel for 12 weeks showed that 68% of patients treated with tazarotene gel and 40% of patients using the vehicle gel had more than a 50% reduction in their total number of inflammatory and noninflammatory acne lesions. Another study showed that 48% of patients treated with tazarotene gel and 29% of patients using the vehicle gel had more than a 50% reduction in their total number of inflammatory and noninflammatory acne lesions. {01}
Psoriasis (treatment)—Tazarotene, as the 0.05% and 0.1% gel, is indicated for the treatment of stable plaque psoriasis involving up to 20% of the body surface area {01}.
—In two studies of patients treated with 0.05% or 0.1% tazarotene gel or with the vehicle gel for 12 weeks, the 0.1% gel was more effective than the 0.05% gel or vehicle gel in the overall improvement of psoriasis. In these studies, 42% and 52% of patients treated with 0.05% tazarotene gel and 52% and 65% of patients treated with 0.1% tazarotene gel showed more than a 50% global improvement from baseline of psoriasis when evaluated for plaque elevation, scaling, and erythema. In the same study, a 50% global improvement over baseline was seen in 23% and 33% of patients treated with the vehicle gel. {01}
Pharmacology/Pharmacokinetics
Physicochemical characteristics:
Chemical group—
Tazarotene is a prodrug that is converted to an acetylenic retinoid, tazarotenic acid {01}.
Molecular weight—
351.47 {02}
Mechanism of action/Effect:
Although tazarotene binds to all three members of the retinoic acid receptor family (alpha, beta, and gamma receptors), it binds selectively to beta and gamma receptors and probably modifies gene expression {01}.
Antiacne agent—The mechanism of action of tazarotene in the treatment of acne vulgaris is not known, but studies suggest that it inhibits corneocyte accumulation in rhino mouse skin and cross-linked envelope formation in human keratocyte cultures {01}.
Antipsoriatic—The mechanism of action of tazarotene in the treatment of psoriasis is not known. Skin studies done with tazarotene in animals and human cell cultures suggest that it has anti-inflammatory and antiproliferative actions in the skin through gene expression. Tazarotene, by directly reducing the keratinocyte's rate of proliferation, helps to normalize cell differentiation and inhibits the formation of a cornified envelope. Also, tazarotene may modify gene transcription or bind to transcription factors to reduce the erythema common in psoriasis {01}.
Absorption:
Minimal systemic absorption of tazarotene occurs because of its rapid metabolism in the skin to the active metabolite, tazarotenic acid, which can be systemically absorbed and further metabolized. The use of a nonradiolabeled dose in one study comparing 0.05% to 0.1% tazarotene showed its area under the plasma concentration–time curve (AUC) as 40% higher for 0.1% gel compared to 0.05% gel. {01}
The percentage of tazarotenic acid absorbed from a dose of 0.1% tazarotene (2 mg per square centimeter [2 mg/cm 2]) and left on the skin for 10 to 12 hours without occlusion is as follows—
• Once a day for 7 days to normal skin (involving 20% of body surface area): 0.91% ± 0.67% tazarotenic acid {01}.
• Once a day for 14 days to psoriatic skin (measurement was extrapolated to 20% of involved area from data using 8 to 18% of body surface area): 14.8% tazarotenic acid {01}.
Distribution:
An in vitro percutaneous absorption study indicated that 4 to 5% of the applied dose remained in the stratum corneum and 2 to 4% remained in the viable epidermis-dermis layer 24 hours after topical application {01}. Tazarotenic acid is hydrophilic and is quickly metabolized systemically, causing no apparent accumulation within body tissues {01}.
Protein binding:
Tazarotenic acid is highly bound to plasma proteins (> 99%) {01}.
Biotransformation:
The prodrug tazarotene undergoes esterase hydrolysis in skin to form its active metabolite, tazarotenic acid. Tazarotenic acid is further metabolized in skin and, after systemic absorption, hepatically metabolized to sulfoxides, sulfones, and other polar products for elimination {01}.
Half-life:
Approximately 18 hours for tazarotenic acid in both normal and psoriatic patients {01}.
Time to peak concentration:
For 0.1% tazarotene:
Dose of 2 mg/cm 2 once a day for 7 days to normal skin (involving 20% of body surface area): 9 hours for tazarotenic acid {01}.
Dose of 2 mg/cm 2 once a day for 14 days to psoriatic skin (measurement was extrapolated to 20% of involved area from data using 8 to 18% of body surface area): 6 hours for tazarotenic acid {01}.
Peak serum concentration:
For 0.1% tazarotene:
Dose of 2 mg/cm 2 once a day for 7 days to normal skin (involving 20% of body surface area): 0.72 ± 5.8 nanogram per mL of tazarotenic acid {01}.
Dose of 2 mg/cm 2 once a day for 14 days to psoriatic skin (measurement was extrapolated to 20% of involved area from data using 8 to 18% of body surface area): 18.9 ± 10.6 nanogram per mL of tazarotenic acid {01}.
Elimination:
Tazarotenic acid—Systemically absorbed dose is eliminated by fecal and renal pathways {01}.
Precautions to Consider
Cross-sensitivity and/or related problems
Patients sensitive to vitamin A or retinoid derivatives, such as acitretin, etretinate, isotretinoin, or tretinoin may be sensitive to this medication {01}.
Carcinogenicity
An 88-week topical application study in mice showed that doses of 0.05, 0.125, 0.25, and 1 mg per kg of body weight (mg/kg) a day produced no carcinogenic effect; a dosage reduction from 1 mg to 0.5 mg/kg a day for male mice after 41 weeks occurred due to severe dermal irritation {01}{03}.
Tumorigenicity
Hairless mice administered topical tazarotene at 0.001%, 0.005%, and 0.01% and exposed to intercurrent ultraviolet radiation for up to 40 weeks developed the expected tumors faster; the clinical relevance to humans is not known {01}{03}.
Mutagenicity
Tazarotene was not found to be mutagenic in a series of tests or assays, including the Ames test, CHO/HPRT mammalian cell forward gene mutation assay, human lymphocyte assay, and the mouse micronucleus test {01}.{03}
Pregnancy/Reproduction
Pregnancy—
Although adequate and well-controlled studies in humans have not been done, tazarotene is not recommended for use during pregnancy because retinoids may cause fetal harm. Apparently healthy babies have been delivered by mothers who were exposed inadvertently to topical tazarotene during early pregnancy; however, tazarotene treatment should be discontinued and the patient advised about potential risks to the fetus if pregnancy occurs. Teratogenic systemic concentrations of the medication may be produced in humans when tazarotene is applied to 20% of body surface area. This may be a concern in treating psoriasis; systemic absorption from treatment of facial acne vulgaris would be less because of the limited area of application. {01}
It is recommended that a pregnancy test, having a sensitivity of 50 milli-International Units (mIU) per mL for human chorionic gonadotropin, be obtained within 2 weeks prior to initiation of treatment with topical tazarotene, and that tazarotene treatment begin during a normal menstrual period. Women of childbearing age also should be counseled about potential risks to the fetus and about available contraceptive options that may be used during tazarotene therapy. {01}{03}
Studies of rats showed lower than expected body weights and reduced skeletal ossification in fetuses when 0.05% tazarotene was used topically during gestation (Days 6 through 17) at a dose of 0.25 mg/kg per day (corresponding to 1.5 mg/m 2 per day). Rabbits that were given topical tazarotene at doses of 0.25 mg/kg per day (corresponding to 2.75 mg/m 2 total body surface area per day) during gestation (Days 6 through 18) showed single incidences of known retinoid malformations, including spina bifida, hydrocephaly, and heart anomalies. {01}
In studies of animals given tazarotene orally, developmental delays were seen in rabbits, and teratogenic effects and postimplantation fetal losses were seen in rats and rabbits at doses that produced serum concentrations between 0.7 and 13 times those produced in humans using topical tazarotene over 20% of the total body surface area. {01}
FDA Pregnancy Category X {01}{03}.
Breast-feeding
It is not known if tazarotene is distributed into breast milk in humans; however, animal studies show that single topical doses of radiolabeled tazarotene are detected in maternal milk {01}. Risk-benefit should be carefully considered {01}.
{03}
Pediatrics
No information is available on the relationship of age to the effects of tazarotene gel in pediatric patients up to 12 years of age. Safety and efficacy have not been established {01}.
No information is available on the relationship of age to the effects of tazarotene cream in pediatric patients up to 18 years of age. Safety and efficacy have not been established {03}.
Geriatrics
Appropriate studies have not been performed in the geriatric population. However, no specific geriatrics problems have been documented to date.{03}
Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):
Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.
Acne products, topical, or topical products containing a peeling agent, such as
Antibiotics, topical, such as clindamycin and erythromycin
Benzoyl peroxide
Resorcinol
Salicylic acid
Sulfur or
Alcohol-containing products, topical, such as
After-shave lotions
Astringents
Cosmetics or soaps with a strong drying effect
Shaving creams or lotions or
Hair products, skin-irritating, such as hair permanents or hair removal products or
Products containing lime or spices, topical or
Soaps or cleansers, abrasive (concurrent use with tazarotene may cause a cumulative irritant or drying effect, especially with the application of peeling, desquamating, or abrasive agents, resulting in excessive irritation of the skin. If irritation results, the strength or dose of tazarotene may need to be reduced or temporarily discontinued until the skin is less sensitive {01})
Photosensitizing medications, such as
Fluoroquinolones
Phenothiazines
Sulfonamides
Tetracyclines
Thiazide diuretics (although tazarotene did not induce contact sensitization, phototoxicity, or photoallergy in human dermal safety studies in patients using tazarotene in the treatment of acne vulgaris {01}, concurrent use with these medications may increase the risk of developing photosensitivity, partly due to tazarotene-induced dryness, peeling, and scaling. These effects are more likely to occur during treatment of psoriasis and may occur anytime during treatment. If skin becomes sunburned or irritated, the strength or dose of tazarotene may need to be reduced or temporarily discontinued until the skin is less sensitive {01})
Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).
Risk-benefit should be considered when the following medical problems exist
» Eczema (tazarotene may cause skin irritation and may worsen this condition {01})
Sensitivity to tazarotene, oral vitamin A{01} , or retinoid derivatives, such as acitretin, etretinate, isotretinoin, or tretinoin
Side/Adverse Effects
Note: A retinoid reaction (erythema, peeling of skin, and stinging or burning sensation of skin) usually occurs with normal use of tazarotene and may be mild. If the retinoid reaction is severe, tazarotene should be discontinued for 1 to 3 days until the symptoms subside and the skin recovers. Symptoms may be less severe for the weaker strength of tazarotene. {01}
The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:
Those indicating need for medical attention
Incidence more frequent
Burning or stinging sensation of the skin, severe {01}
desquamation, severe (severe peeling of skin; severe dryness of skin){01}
erythema, severe (severe redness of skin){01}
fissuring of skin (deep grooves or lines in skin){01}
localized edema (pain or swelling of treated skin){01}
pruritus, severe (severe itching of skin){01}
skin discoloration (change in color of treated skin){01}
For patients with psoriasis only
Irritant contact dermatitis (skin rash)—incidence of 1 to 10%{01}
Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent—can indicate therapeutic effect
Burning or stinging sensation of the skin, mild —on application{01}
desquamation, mild (mild peeling of skin; mild dryness of skin){01}
erythema, mild (mild redness of skin){01}
pruritus, mild (mild itching of skin){01}
Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Tazarotene (Topical) .
In providing consultation, consider emphasizing the following selected information (» = major clinical significance):
Before using this medication
» Conditions affecting use, especially:
Sensitivity to tazarotene, oral vitamin A, or retinoid derivatives
Tumorigenicity—
The development rate of expected skin tumors induced by ultraviolet light in mice treated with topical tazarotene was faster than in light-exposed mice not treated with tazarotene; clinical relevance to humans is not known
Pregnancy—Not recommended for use during pregnancy; initiation of treatment is recommended during menses after a pregnancy test, and contraception should be considered during treatment
Breast-feeding—Although it is not known if medication is distributed into breast milk, use is not recommended while breast-feeding
Other medical problems, especially eczema
Proper use of this medication
» Importance of not using more medication than the amount prescribed
Reading patient directions carefully before use
Proper administration
For treatment of acne vulgaris
Before applying tazarotene, washing skin with mild or nonallergenic soap or cleanser and warm water; gently patting dry; waiting at least 20 to 30 minutes before applying medication
For treatment of acne vulgaris or psoriasis
» Avoiding contact with the eyes, mouth, and nose; spreading away from these areas when applying medication
» Not applying medication to windburned or sunburned skin or to open wounds
» Waiting for 20 to 30 minutes to allow complete drying of skin if recently washed; applying to wet skin can cause skin irritation
Applying very sparingly to affected areas only and rubbing in gently but well; washing medication off areas not intended to be treated
Washing hands immediately after administration
» Proper dosing
Missed dose: Applying next dose at regularly scheduled time; not doubling doses
» Proper storage
Precautions while using this medication
» Discontinuing medication and contacting physician if pregnancy is suspected
For treatment of acne vulgaris—Condition may appear to worsen during the first 3 weeks of therapy; checking with health care professional if acne does not improve within 8 to 12 weeks
For treatment of psoriasis—Condition may worsen at any time during treatment; checking with health care professional if this occurs
Not covering treated area with a bandage
Either checking with health care professional before using or avoiding use of other topical acne or skin products containing a peeling agent (e.g., benzoyl peroxide, resorcinol, salicylic acid, or sulfur), irritating hair products (permanents or hair removal products), sun-sensitizing skin products (including products containing limes or spices), alcohol-containing skin products, or drying or abrasive skin products (some cosmetics or soaps or skin cleansers)
Avoiding use of vitamin A supplements while using tazarotene, unless otherwise directed by health care professional
Minimizing exposure of treated areas to sunlight, wind, and cold temperatures to lessen the possibility of sunburn, dryness, or irritation. Also, avoiding use of artificial sunlight (sunlamps).
Using sunscreen preparations (minimum sun protection factor [SPF] of 15) or wearing protective clothing over treated areas when skin exposure cannot be avoided
Side/adverse effects
Signs of potential side effects, especially burning or stinging sensation of the skin (severe), desquamation (severe), erythema (severe), fissuring of skin, irritant contact dermatitis—for treatment of psoriasis only, localized edema, pruritus (severe), or skin discoloration
Skin usually becomes irritated with normal use and administration; checking with doctor at any time skin becomes too dry or irritated
General Dosing Information
Use of adequate birth control in women of reproductive age who are using tazarotene should be discussed, especially during treatment of psoriasis involving 20% of total body surface area {01}.
If tazarotene causes too much skin irritation or peeling, it should not be applied until the skin is healed or less irritated. Tazarotene should not be applied to mucous membranes; administration near the eyes, lips, or nose should be avoided. {01}{03}
Patients should be counseled on the importance of protecting the skin from the sun, wind, cold temperatures, and excessive dryness by using sunscreens of at least SPF 15, moisturizers, and protective clothing. Artificial sunlight, such as sunlamps, should be avoided. {01}{03}
Topical products or medications should not be applied simultaneously with tazarotene; occlusive bandages should not be applied to treated areas {01}.
Using the fingertips when washing the skin helps clean the skin and remove resulting scales and peeling of skin; harsh scrubbing of skin with sponges or washcloths should be avoided {01}.
Tazarotene should be applied to dry skin (20 to 30 minutes should be allowed after washing) to reduce possible skin irritation that worsens or occurs more often if tazarotene is applied any earlier to nondry skin {01}.
If emollients are used, they should be applied at least one hour before application of tazarotene.{03}
For the treatment of acne
The areas to be treated for acne should be cleansed thoroughly before the medication is applied {01}.
Within the first few weeks, acne can worsen because of exacerbation of deep, previously unseen lesions {01}.
Therapeutic results with use of tazarotene may be noticeable after 4 weeks of therapy; clinical investigations beyond 12 weeks have not been done {01}.
For the treatment of psoriasis
Therapeutic results on psoriatic lesions and scales may be noticeable after 1 to 4 weeks of therapy, but improvement of the skin redness may take longer. Clinical investigations beyond 1 year have not been done {01}.
During a 1-year study, psoriasis worsened for some patients throughout the treatment period; worsening of the condition should be reported to physician {01}.
The patient should apply tazarotene carefully only to affected skin to minimize the amount of skin irritation {01}.
The safety of using tazarotene over more than 20% of total body surface area has not been established, and systemic absorption would be expected {01}.
The efficacy of less than once daily use of tazarotene cream has not been established.{03}
Topical Dosage Forms
TAZAROTENE CREAM
Usual adult dose
Psoriatic lesions
Topical, apply to dry, affected areas of the skin once a day in the evening. Use enough to cover lesions (2 mg/cm 2) with a thin film.
{03}
Usual pediatric dose
Safety and efficacy have not been established.
{03}
Strength(s) usually available
U.S.—
0.05% (Rx) [Tazorac (carbomer 934P) ( carbomer 1342) (edetate disodium) (medium chain triglycerides) (mineral oil) (purified water) ( sodium thiosulfate) (sorbitan monooleate) (sodium hydroxide)]{03}
0.1 % (Rx) [Tazorac (carbomer 934P) ( carbomer 1342) (edetate disodium) (medium chain triglycerides) (mineral oil) (purified water) ( sodium thiosulfate) (sorbitan monooleate) (sodium hydroxide)]{03}
Packaging and storage:
Store at 25 °C (77 °F), excursions permitted from –5 to 30 °C (23 to 86 °F).{03}
Auxiliary labeling:
• For external use only.{03}Avoid contact with eyes, eyelids and mouth. If contact with eyes occurs rinse thoroughly with water.{03}
• Avoid prolonged or excessive exposure to direct and/or artificial sunlight while using this medication.{03}
Note: Include patient instructions when dispensing{03}.
TAZAROTENE GEL
Usual adult dose
Acne vulgaris
Topical, (as the 0.1% gel) to clean, dry affected areas of facial skin, once a day, usually in the evening or at bedtime {01}.
Psoriasis
Topical, (as the 0.05 or 0.1% gel) to affected areas of skin, once a day at bedtime. Treated area should not exceed 20% of total body surface area {01}.
Usual pediatric dose
Safety and efficacy have not been established {01}.
Strength(s) usually available
U.S.—
0.05% (Rx) [Tazorac (ascorbic acid) (benzoyl alcohol 1% w/w) (butylated hydroxyanisole) (butylated hydroxytoluene) (carbomer 934P) (edetate disodium) (hexylene glycol) (poloxamer 407) (polyethylene glycol 400) (polysorbate 40) (purified water) ( tromethamine){01}]
0.1% (Rx) [Tazorac (ascorbic acid) (benzoyl alcohol 1% w/w) (butylated hydroxyanisole) (butylated hydroxytoluene) (carbomer 934P) (edetate disodium) (hexylene glycol) (poloxamer 407) (polyethylene glycol 400) (polysorbate 40) (purified water) ( tromethamine){01}]
Packaging and storage:
Store below 25 °C (77 °F), preferably between 15 and 30 °C (59 and 86 °F), in a tight container {01}.
Auxiliary labeling:
• For external use only.
• Avoid prolonged or excessive exposure to direct and/or artificial sunlight while using this medication.
Note: Include patient instructions when dispensing {01}.
Developed: 11/14/1997
Revised: 03/05/2001
References
- Tazorac Gel package insert (Allergan Herbert—US), Rev 6/97, Rec 6/97.
- Canada JR, editor. USP dictionary of USAN and international drug names 1998. Rockville, MD: The United States Pharmacopeial Convention, Inc; 1997. p. 374.
- Product Information: Tazorac® Cream, tazarotene. Allergan, Irvine, CA (PI issued 09/2000) PI Reviewed 02/2001.
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