Tazarotene

Class: Skin and Mucous Membrane Agents, Miscellaneous
ATC Class: D05AX05
VA Class: DE752
Molecular Formula: C21H21NO2S
CAS Number: 118292-40-3
Brands: Tazorac, Avage

Introduction

Synthetic acetylenic retinoid.1 2 3 4 5 6 7 16 19

Uses for Tazarotene

Psoriasis

Treatment of stable plaque psoriasis with ≤20% body surface area involvement.1 3 4 16 19

Combination therapy with a mid-or high-potency topical corticosteroid more effective than either agent alone.21 22 23

0.1% cream or gel more effective in improving psoriasis manifestations;1 19 0.05% cream or gel associated with less local irritation.1 4 17 19

Slideshow: Psoriasis: Treatment Options to Manage Your Symptoms

Acne

Treatment of mild to moderate acne vulgaris.1 6 7 19

Efficacy in patients resistant to oral antibiotics or previously treated with other retinoids not established.1

Photoaging

Palliative therapy to improve dermatologic changes (e.g., fine wrinkling, mottled hypo- or hyperpigmentation, benign lentigines) associated with photodamage.27

Use as an adjunct to a comprehensive skin care plan and sun avoidance program.27 (See Administration under Dosage and Administration.)

Does not eliminate or prevent wrinkles, repair photodamaged skin, reverse photoaging, or restore youthful or younger dermal histologic pattern.27 No mitigating effects on severe manifestations of chronic sunlight exposure (e.g., coarse/deep wrinkling, tactile roughness, telangiectasia, skin laxity, keratinocytic atypia, melanocytic atypia, dermal elastosis) demonstrated.27

Safety and efficacy not established for use in nonwhite (e.g., Asian, Hispanic) patients or Fitzpatrick skin types V and VI.27

Tazarotene Dosage and Administration

General

  • Excessive use does not increase therapeutic effect and may produce marked inflammatory reactions (e.g., erythema, peeling, discomfort).1 19 27 (See Dermatologic Effects under Cautions.)

Administration

Topical Administration

Apply topically to the skin as a cream or gel.1 19 27

For dermatologic use only; avoid contact with mouth, eyes, and other mucous membranes.1 19 27

Wash hands after applying cream or gel (unless the hands are being treated for psoriasis).1 19 27

Occlusive dressings or wrappings should not be used.d e

A transient feeling of pruritus, burning, or stinging may occur after application.1 17 19

If irritation is excessive, temporarily discontinue therapy, reduce dosage strength (in patients with psoriasis), or decrease frequency of applications; reinitiate therapy or increase drug concentration or application frequency when patient is able to tolerate the drug.1 19 27 Closely monitor patient response and tolerance to changes in drug concentration or application frequency.19 27

Psoriasis

Apply a sufficient amount (2 mg/cm2) of cream or gel to cover affected area lightly.1 19

Apply cream or gel to dry skin.1 19 If required, apply moisturizer ≥1 hour prior to applying cream or gel; apply tazarotene only after ensuring that there is no more moisturizer on skin surface.1 19

Avoid application of cream or gel to unaffected skin; these areas may be more susceptible to irritation.1 17 19 (See Dermatologic Effects under Cautions.)

Acne

Gently wash and dry affected area(s) prior to application.1 19

Apply a sufficient amount of 0.1% cream or gel (2 mg/cm2) to cover all lesions with a thin film.1 19

Photoaging

Apply 0.1% cream topically to the face; use the minimum amount necessary to cover the face (including eyelids if desired) lightly; avoid eyes and mouth.27

Gently wash face with mild soap, pat and dry, and wait 20–30 minutes before applying tazarotene cream to face.27

Moisturizers may be applied to skin before or after application of tazarotene; however, allow first topical preparation to absorb into the skin and dry completely before applying the second preparation.27

Administer in conjunction with a comprehensive skin care plan and a sun avoidance program;27 apply a moisturizing sunscreen (≥15 SPF) every morning.27

Dosage

Pediatric Patients

Acne
Topical

Children >12 years of age: Apply a sufficient amount (2 mg/cm2) of 0.1% cream or gel once daily in the evening.1 19

Improvement usually is detectable within 4 weeks of initiating therapy.d

Adults

Psoriasis
Topical

Initially, apply 0.05% cream or gel (2 mg/cm2) once daily in the evening.1 19

If tolerated and clinically indicated, increase to 0.1% cream or gel once daily in the evening; if excessive skin irritation occurs, reduce concentration to 0.05%.19 a

Improvement in psoriasis plaques and scales usually is detectable within 1–4 weeks of initiating therapy; improvement in erythema may take longer.d

Acne
Topical

Apply a sufficient amount (2 mg/cm2) of 0.1% cream or gel once daily in the evening.1 19

Therapeutic effects may require >4 weeks of therapy.d e

Photoaging
Topical

Apply a pea-sized amount (5-mm or ¼-inch diameter) of the 0.1% cream to the face once daily at bedtime.f 27

Prescribing Limits

Efficacy of application less than once daily not established.a 19 27

Pediatric Patients

Acne
Topical

Children ≥12 years of age: In clinical studies, therapy did not exceed 12 weeks.1 3 4 5 8 19

Adults

Psoriasis
Topical

Safety and efficacy of therapy with 0.05% and 0.1% gel for >12 months not established.a

Safety of application to >20% of body surface area not established.1

Acne
Topical

Safety and efficacy of therapy with 0.1% cream or gel for >12 weeks not established.a b

Photoaging
Topical

Safety and efficacy of therapy with 0.1% cream for >52 weeks not established.27

Cautions for Tazarotene

Contraindications

  • Known or suspected pregnancy.1 19 27 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

  • Known hypersensitivity to tazarotene or any ingredient in the formulation.1 19 27

Warnings/Precautions

Warnings

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm;9 10 11 12 13 14 15 19 27 teratogenicity and embryotoxicity demonstrated in animals receiving topical and oral tazarotene.1 19 27

Systemic exposure depends on amount of body surface area treated.19 Level of exposure to produce teratogenic effects in humans unknown.19 27

Exclude pregnancy using a reliable blood pregnancy test with a sensitivity of ≥50 mIU/mL for human chorionic gonadotropin (HCG) within 2 weeks before initiating tazarotene; initiate therapy during next normal menstrual period.1 19 27

Use adequate forms of contraception during tazarotene therapy.1 19 27

If pregnancy occurs, immediately discontinue and apprise of potential fetal hazard.1 19 27

Sensitivity Reactions

Photosensitivity

Increased risk of sunburn.1

Cautious use recommended in patients subjected to considerable occupational sun exposure and those with inherent sensitivity to the sun; use of sunscreen products (≥SPF 15) and protective clothing over treated areas recommended when exposure cannot be avoided.1 19 27

Caution recommended with concomitant use of photosensitizing agents.1 19 27 (See Specific Drugs under Interactions.)

Use not recommended for patients with sunburn until full recovery occurs.1 19 27

Minimize exposure of treated area(s) to sunlight and avoid use of sunlamps.1 19 27

General Precautions

Use in Patients with Eczema

Possible severe irritation of eczematous skin.1 19 27 Use not recommended in patients with eczema.1 19 27

Dermatologic Effects

Possible severe erythema, pruritus, burning, or stinging.1 19 c If irritation is excessive, discontinue therapy temporarily until skin integrity restored, or reduce dosing to a concentration (in patients with psoriasis) or interval patient can tolerate; however, efficacy of reduced dosing frequencies (i.e., < once daily) not established.1 19 27 (See Dosage under Dosage and Administration.)

Avoid contact of the drug with mouth, eyes, and other mucous membranes.1 19 27 If ocular contact occurs, affected eye(s) should be flushed with copious amounts of cool water; consult clinician if ocular irritation persists.1 19 27

Environmental Stimuli

Possible increased skin irritation in patients exposed to environmental extremes (e.g., wind, cold).1 19 27

Lentigo maligna

Facial pigmented lesions should be assessed by a clinician before application of tazarotene therapy for photoaging.c Lentigo maligna should not be treated with tazarotene.c

Specific Populations

Pregnancy

Category X.1 19 27 (See Fetal/Neonatal Morbidity and Mortality and also Contraindications under Cautions.)

Lactation

Not known whether topical tazarotene distributed into human milk; caution advised if topical tazarotene used.1 19 27

Pediatric Use

Safety and efficacy not established for treatment of psoriasis in children <18 years of age, for treatment of acne in children <12 years of age, or for treatment of photoaging in children <17 years of age.a 19 27

Geriatric Use

Safety and/or efficacy for treatment of psoriasis and photoaging in those >65 years of age similar to that in younger adults; possibility exists of greater sensitivity to the drug in geriatric individuals.19 27

Safety and efficacy not evaluated for treatment of acne in patients >65 years of age.19

Common Adverse Effects

In patients with psoriasis: Pruritus, erythema, burning/stinging, worsening of psoriasis, irritation, skin pain.1 19 27

In patients with acne: Desquamation, burning/stinging, dry skin, erythema, pruritus.1 19 27

In patients treated for photoaging: Desquamation, erythema, burning, dry skin, skin irritation, pruritus.1 19 27

Interactions for Tazarotene

Specific Drugs

Drug

Interaction

Comments

Photosensitizing agents (e.g., fluoroquinolone anti-infectives, phenothiazines, sulfonamides, tetracyclines, thiazide diuretics)

Possible increased photosensitivity 1 19 27 (See Photosensitivity under Cautions.)

Use concomitantly with cautiona b c

Other Topical Preparations

Potential pharmacodynamic interaction (increased skin irritation).1 19 27 Avoid concomitant use of topical preparations with high concentrations of alcohol, menthol, spices, or lime (e.g., lotions, astringents, perfume);1 17 19 27 irritating cosmetics (e.g., toners, peeling [desquamating] agents); permanent wave solutions; electrolysis; hair depilatories; or other preparations or processes that might dry or irritate the skin.1 19 27 Allow time for effects of skin-drying preparations to subside before initiating tazarotene therapy.1 19 27

Tazarotene Pharmacokinetics

Absorption

Bioavailability

Minimally absorbed following topical application;a b c however, systemic exposure depends on the extent of body surface area treated.19 c

Distribution

Extent

Not known whether topical tazarotene distributed into human milk.1 19 27

Plasma Protein Binding

>99%.a b c

Elimination

Metabolism

Metabolized via esterase hydrolysis to active metabolite, tazarotenic acid.a b c Other metabolites (i.e., sulfoxides, sulfones, and other polar metabolites) have been identified.a b c

Elimination Route

Excreted principally in urine and feces.a b c

Half-life

Tazarotenic acid: approximately 18 hours.a b c

Stability

Storage

Topical

Cream

25°C (may be exposed to -5–30°C).b c

Gel

25°C (may be exposed to 15–30°C).a

Actions

  • Pharmacologic actions similar to other retinoids (e.g., vitamin A, tretinoin, isotretinoin); however, tazarotene shows selective affinity for specific nuclear retinoic acid receptor (RAR) proteins RARβ and RARγ and may modify gene expression.2 6 7 16 a b c

  • Exact mechanism(s) of action for treatment of psoriasis not determined.1 19 May affect expression of genes that modulate cell (e.g., epidermal) differentiation, proliferation, and inflammation,2 3 5 6 7 16 leading to normalization of keratinocyte differentiation and reduced cellular hyperproliferation and inflammation.16 19 a

  • Exact mechanism(s) of action for treatment of acne not fully understood.1 Appears to modulate follicular keratinization, cell proliferation, and inflammation resulting in inhibition of corneocyte accumulation and cohesion and decreased inflammatory and noninflammatory acne lesions.6 7 19 a

  • Exact mechanism(s) of action in the treatment of photoaging not determined.27 May increase the number of granular cell layers and increase the incidence of epidermal edema.27

Advice to Patients

  • Importance of clinicians instructing patients about proper use of the drug, including associated precautions.1 19 Provide copy of the manufacturer's patient instructions.a b c d e f

  • Importance of women informing clinician if they are or plan to become pregnant or plan to breast-feed.1 19 27 Necessity for clinicians to describe risk of birth defects and to advise women to avoid pregnancy by using adequate methods of contraception during therapy.1 19 27 (See Fetal/Neonatal Morbidity and Mortality under Warnings.)

  • Importance of avoiding excessive use of topical tazarotene.d e f

  • Importance of contacting clinician if dermatologic condition worsens with tazarotene therapy.1 19

  • Importance of avoiding use of shaving lotions, astringents, perfume, toners, peeling (desquamating) agents, permanent wave solutions, electrolysis, hair depilatories, or other preparations or processes that might irritate the skin.1 17 19 27

  • Importance of consulting clinician regarding specific instructions for routine skin care, use of cosmetics, moisturizers, and sunscreens.27 c

  • Importance of adhering to prescribed directions for use; avoid contact with eyes, mouth, or mucous membranes.1 19 27

  • Importance of informing patients that treated areas of the skin should not be bandaged or otherwise covered or wrapped so as to be occlusive unless directed by their clinician.d e

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and cosmetic products or procedures.a b c

  • Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Tazarotene

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Topical

Cream

0.05% w/w

Tazorac (with benzyl alcohol 1% w/w)

Allergan

0.1% w/w

Avage (with benzyl alcohol 1% w/w)

Allergan

Tazorac (with benzyl alcohol 1% w/w)

Allergan

Gel

0.05% w/w

Tazorac (with benzyl alcohol 1% w/w)

Allergan

0.1% w/w

Tazorac (with benzyl alcohol 1% w/w)

Allergan

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions May 1, 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Allergan. Tazorac (tazarotene) topical gel prescribing information. Irvine, CA; 1998 Dec

2. Chandraratna RAS. Tazarotene-first of a new generation of receptor-selective retinoids. Br J Dermatol. 1996; 135:18-25.

3. Marks R. Early clinical development of tazarotene. Br J Dermatol. 1996; 135(Suppl 49):26-31. [IDIS 374855] [PubMed 9035702]

4. Weinstein GD. Safety, efficacy and duration of therapeutic effect of tazarotene used in the treatment of plaque psoriasis. Br J Dermatol. 1996; 135(Suppl 49):32-6. [IDIS 374856] [PubMed 9035703]

5. Esgleyes-Ribot T, Chandraratna RA, Lew-Kaya DA et al. Response of psoriasis to a new topical retinoid, AGN 190168. J Am Acad Dermatol. 1994; 30:581-90. [IDIS 327735] [PubMed 7512583]

6. Thiboutot DM. Acne-an overview of clinical research findings. Dermatol Clin. 1997; 15:97-109. [PubMed 9001864]

7. Gibson JR. Rationale for the development of new topical treatments for acne vulgaris. Cutis. 1996; 57(Suppl 1):13-19. [PubMed 8654127]

8. Shalita AR, Chalker DK, Griffith RF et al. Double-blind study of AGN 19018, a new retinoid gel, in the topical treatment of acne vulgaris. J Invest Dermatol. 1993; 100:542.

9. Anon. Update on birth defects with isotretinoin. FDA Drug Bull. 1984; 14:15-6. [PubMed 6592122]

10. Roche Laboratories. Accutane (isotretinoin) capsule prescribing information. Nutley, NJ; 1990 May.

11. Benke PJ. The isotretinoin teratogen syndrome. JAMA. 1984; 251:3267-9. [IDIS 186330] [PubMed 6587131]

12. de la Cruz E, Sun S, Vangvanichyakorn K et al. Multiple congenital malformations associated with maternal isotretinoin therapy. Pediatrics. 1984; 74:428-30. [IDIS 189774] [PubMed 6591112]

13. Lammer EJ, Chen DT, Hoar RM et al. Retinoic acid embryopathy. N Engl J Med. 1985; 313:837-41. [IDIS 204599] [PubMed 3162101]

14. Rosa FW, Wilk AL, Kelsey FO. Teratogen update: vitamin A congeners. Teratology. 1986; 33:355-64. [PubMed 3461576]

15. Cohen M, Rubenstein A, Li JK et al. Thymic hypoplasia associated with isotretinoin embryopathy. Am J Dis Child. 1987; 141:263-6. [IDIS 226304] [PubMed 3492909]

16. Nagpal S, Thacher SM, Patel S et al. Negative regulation of two hyperproliferative keratinocyte differentiation markers by a retinoic acid receptor-specific retinoid: insight into the mechanism of retinoid action in psoriasis. Cell Growth Differ. 1996; 7:1783-91.

17. Allergan. Irvine, CA: Personal communication.

18. Weinstein GD. Tazarotene gel: efficacy and safety in plaque psoriasis. J Am Acad Dermatol. 1997; 37:S33-8.

19. Allergan. Tazorac (tazarotene) cream prescribing information. Irvine, CA; 2001 Oct.

20. Shalita AR,, Chalker DK, Griffith RF et al. Tazarotene gel is safe and effective in the treatment of acne vulgaris: a multicenter, double-blind, vehicle-controlled study. Cutis. 1999; 63:349-54. [PubMed 10388959]

21. Gollnick H, Menter A. Combination therapy with tazarotene plus a topical corticosteroid for the treatment of plaque psoriasis. Br J Dermatol. 1999; 140(suppl 54):18-23. [IDIS 427533] [PubMed 10731130]

22. Lebwohl M. Strategies to optimize efficacy, duration of remission, and safety in the treatment of plaque psoriasis by using tazarotene in combination with a corticosteroid. J Am Acad Dermatol. 2000; 43(2 Pt 3):S43-6.

23. Green L, Sadoff W. A clinical evaluation of tazarotene 0.1% gel, with and without a high- or mid-high-potency corticosteroid, in patients with stable plaque psoriasis. J Cutan Med Surg. 2002; 6:95-102. [PubMed 11992180]

24. Webster GF, Guenther L, Poulin YP et al. A multicenter, double-blind, randomized comparison study of the efficacy and tolerability of once-daily tazarotene 0.1% gel and adapalene 0.1% gel for the treatment of facial acne vulgaris. Cutis. 2002; 69(Suppl 2):4-11. [PubMed 12095066]

25. Webster GF, Berson D, Stein LF et al. Efficacy and tolerability of once-daily tazarotene 0.1% gel versus once-daily tretinoin 0.025% gel in the treatment of facial acne vulgaris: a randomized trial. Cutis. 2001; 67(Suppl 6):4-9. [PubMed 11499329]

26. Leyden JJ, Tanghetti EA, Miller B et al. Once-daily tazarotene 0.1% gel versus once-daily tretinoin 0.1% Microsponge gel for the treatment of facial acne vulgaris: a double-blind randomized trial. Cutis. 2002; 69(Suppl 2):12-9. [PubMed 12095064]

27. Allergan, Inc. Avage (tazarotene) cream, 0.1% prescribing information. Irvine, CA; 2002 Oct.

28. Kang S, Leyden JJ, Lowe NJ et al. Tazarotene cream for the treatment of facial photodamage: a multicenter, investigator-masked, randomized, vehicle-controlled, parallel comparison of 0.01%, 0.025%, 0.05%, and 0.1% tazarotene creams with 0.05% tretinoin emollient cream applied once daily for 24 weeks. Arch Dermatol. 2001; 137:1597-604. [IDIS 474505] [PubMed 11735710]

29. Phillips TJ, Gottlieb AB, Leyden JJ et al. Efficacy of 0.1% tazarotene cream for the treatment of photodamage: a 12-month multicenter, randomized trial. Arch Dermatol. 2002; 138:1486-93. [IDIS 489273] [PubMed 12437455]

a. Allergan. Tazorac (tazarotene) topical gel 0.5 and 0.1% prescribing information. Irvine, CA; 2004 Jan.

b. Allergan. Tazorac (tazarotene) cream prescribing information. Irvine, CA; 2004 May.

c. Allergan, Inc. Avage (tazarotene) cream, 0.1% prescribing information. Irvine, CA; May 2004.

d. Allergan Inc. Tazorac (tazarotene) topical gel, 0.5 and 0.1%, information for patients. Irvine, CA: 2004 Jan.

e. Allergan Inc. Tazorac (tazarotene) topical cream, 0.5 and 0.1%, information for patients. Irvine, CA: 2004 May.

f. Allergan Inc. Avage (tazarotene) cream, 0.1%, patient information. Irvine, CA: 2004 May.

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