Tazarotene - Drug Monograph

Introduction

Tazarotene is a third-generation topical retinoid prodrug specifically designed for dermatological applications. It belongs to the acetylenic class of retinoids and is classified as a retinoid receptor-selective agent. First approved by the FDA in 1997, tazarotene has established itself as a valuable therapeutic option for various dermatological conditions, particularly those involving keratinization disorders and photoaging.

Mechanism of Action

Tazarotene is a prodrug that undergoes rapid hydrolysis to its active metabolite, tazarotenic acid, upon application to the skin. Tazarotenic acid binds selectively to retinoic acid receptors (RARs), specifically RAR-β and RAR-γ, which are present in epithelial tissues. This binding modulates gene expression, resulting in:

• Normalization of keratinocyte differentiation
• Reduction of hyperproliferation in psoriatic plaques
• Inhibition of comedogenesis in acne vulgaris
• Modulation of inflammatory mediators
• Increased collagen production in photoaged skin
• Regulation of cellular apoptosis

The drug's receptor selectivity contributes to its therapeutic efficacy while potentially minimizing systemic retinoid toxicity.

Indications

• Plaque psoriasis (0.05% and 0.1% creams and gels)
• Acne vulgaris (0.05% and 0.1% gels)
• Facial photodamage (0.1% cream)

• Treatment of pityriasis rubra pilaris
• Management of Darier's disease
• Treatment of lamellar ichthyosis
• Improvement of striae distensae
• Management of plane warts

Dosage and Administration

• Plaque psoriasis: Apply thin film to affected areas once daily, preferably in evening
• Acne vulgaris: Apply thin film to entire affected area once daily, after cleansing
• Photodamage: Apply pea-sized amount to entire face once daily, in evening

• Geriatric patients: No dosage adjustment required
• Renal impairment: Use with caution; limited data available
• Hepatic impairment: Use with caution; limited data available
• Pediatric patients: Safety and efficacy not established for children under 12 years

• Apply to clean, dry skin
• Avoid application to eyes, mouth, angles of nose, and mucous membranes
• Use moisturizers to minimize irritation
• Initiate therapy with less frequent application (every other day) if irritation occurs

Pharmacokinetics

• Minimal systemic absorption following topical application
• Approximately 1-5% of applied dose reaches systemic circulation
• Absorption increased with application to broken or inflamed skin

• Tazarotenic acid highly bound to plasma proteins (>99%)
• Distributed to various tissues, with minimal accumulation

• Rapidly hydrolyzed to active metabolite tazarotenic acid
• Undergoes oxidation, conjugation, and further degradation
• Metabolized via cytochrome P450 system

• Primarily eliminated through hepatobiliary system
• Renal excretion accounts for <1% of eliminated dose
• Half-life of tazarotenic acid is approximately 18 hours

Contraindications

• Hypersensitivity to tazarotene or any component of the formulation
• Pregnancy (Category X) and women attempting to conceive
• Breastfeeding (due to potential secretion in breast milk)
• Use on eczematous skin or other acute inflammatory conditions

Warnings and Precautions

• Category X: Demonstrated fetal abnormalities in animal studies
• Women of childbearing potential must use effective contraception
• Pregnancy testing recommended before initiation

• Significant skin irritation may occur, especially during initial treatment
• Photosensitivity: Patients should use sunscreen and protective clothing
• Avoid application to sunburned skin
• Caution in patients with history of eczema or other skin conditions

• Potential for systemic absorption, especially with extensive application
• Monitor for signs of hypervitaminosis A in patients applying to large body surface areas

Drug Interactions

• Increased irritation with concomitant use of other topical medications (especially drying agents, abrasives, or alcohol-containing products)
• Avoid concurrent use with other topical retinoids

• Potential interaction with drugs metabolized by CYP450 system
• Theoretical increased risk of hepatotoxicity with other hepatotoxic drugs
• No clinically significant interactions with systemically administered drugs documented

Adverse Effects

• Application site reactions: erythema, pruritus, burning, irritation (20-30%)
• Dryness and scaling (10-20%)
• Skin pain and stinging (5-15%)
• Photosensitivity reactions (2-5%)

• Contact dermatitis
• Skin discoloration
• Skin inflammation
• Exacerbation of psoriasis

• Severe skin irritation requiring discontinuation
• Hypersensitivity reactions
• Signs of systemic retinoid toxicity (with extensive application)

Monitoring Parameters

• Skin response and tolerance at each follow-up visit
• Signs of excessive irritation or inflammation
• Therapeutic efficacy for indicated condition
• Pregnancy status in women of childbearing potential

• Generally not required for standard topical use
• Consider liver function tests if applying to >20% body surface area
• Pregnancy testing as indicated

• Report severe irritation, blistering, or crusting
• Monitor for signs of hypersensitivity
• Observe for changes in pigmentation

Patient Education

• Use exactly as prescribed; more frequent application increases irritation risk
• Apply thin layer to affected areas only
• Wash hands thoroughly after application
• Allow skin to dry completely before application

• Use broad-spectrum sunscreen daily (SPF 15 or higher)
• Avoid excessive sun exposure and artificial UV light
• Moisturize regularly to minimize dryness
• Avoid waxing treated areas due to increased skin fragility

• Discontinue use if severe irritation occurs
• Inform all healthcare providers about tazarotene use
• Women must use effective contraception during treatment
• Avoid use during pregnancy and breastfeeding

• Improvement may be seen within 2-4 weeks for acne
• Psoriasis improvement typically seen within 1-2 months
• Photodamage improvement may require 6-12 months of treatment
• Initial worsening of condition may occur before improvement

References

1. FDA prescribing information: Tazorac (tazarotene) cream and gel 2. Lebwohl M, et al. J Am Acad Dermatol. 1998;39(2 Pt 3):S123-S127 3. Weinstein GD, et al. J Am Acad Dermatol. 1997;37(1):85-92 4. Bershad S, et al. Arch Dermatol. 2002;138(4):481-489 5. Kang S, et al. J Am Acad Dermatol. 2005;52(2):268-274 6. Phillips TJ, et al. Arch Dermatol. 2002;138(5):606-613 7. Drug Facts and Comparisons. Wolters Kluwer Health, 2023 8. UpToDate: Tazarotene drug information, 2023 9. Clinical Pharmacology [database online]. Tampa, FL: Elsevier; 2023 10. American Academy of Dermatology guidelines for topical retinoid use, 2022