TAZORAC
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TAZORAC (TAZORAC).
Tazarotene is a retinoid prodrug that is converted to its active metabolite, tazarotenic acid, which binds to retinoic acid receptors (RAR-β, RAR-γ) with high affinity, modulating gene expression involved in cell proliferation, differentiation, and inflammation.
| Metabolism | Tazarotene is rapidly metabolized via ester hydrolysis to its active metabolite, tazarotenic acid. Further metabolism includes oxidation and conjugation. The metabolic pathways involve esterases and cytochrome P450 (CYP) enzymes, primarily CYP2C8, with minor contributions from CYP3A4 and CYP2C9. |
| Excretion | Primarily fecal: approximately 60-70% eliminated in feces (as metabolites), renal excretion accounts for <10% as unchanged drug and metabolites, with <1% as unchanged tazarotenic acid. |
| Half-life | Terminal elimination half-life of tazarotenic acid is approximately 18 hours (range 7-30 hours) after topical application, allowing once-daily dosing; systemic exposure is low due to extensive protein binding and slow clearance. |
| Protein binding | Highly protein-bound (>99%), primarily to albumin and also to alpha-1-acid glycoprotein. |
| Volume of Distribution | Volume of distribution for tazarotenic acid is approximately 1.5 L/kg (range 0.5-3.0 L/kg), indicating distribution into total body water and extensive tissue binding, particularly in skin. |
| Bioavailability | Bioavailability after topical application: 1-5% of the applied dose is absorbed systemically (based on urinary and fecal recovery of radiolabeled drug), with minimal systemic exposure; oral bioavailability has been studied but is not clinically relevant as the drug is used topically. |
| Onset of Action | Onset of clinical effect is within 1 to 2 weeks after topical application for plaque psoriasis; for acne vulgaris, improvement may be seen within 4 weeks. |
| Duration of Action | Duration of action lasts for the dosing interval (24 hours), with sustained improvement over weeks to months of continued therapy; residual effects may persist for several days after discontinuation due to drug retention in skin. |
| Molecular Weight | 351.46 |
Apply a pea-sized amount to affected areas once daily in the evening. Tazorac is available as a 0.05% or 0.1% gel or cream. For plaque psoriasis, the 0.1% gel is typically used. For acne, the 0.1% cream or gel is started, then decreased to 0.05% if irritation occurs.
| Dosage form | CREAM |
| Renal impairment | No specific dose adjustment recommended for renal impairment. Use with caution in severe renal disease due to lack of data. |
| Liver impairment | No specific dose adjustment recommended for hepatic impairment. Use with caution in severe hepatic disease due to lack of data. |
| Pediatric use | Not recommended for use in children <12 years of age for acne; safety and efficacy not established. For psoriasis, use in adolescents ≥12 years: apply 0.05% or 0.1% gel once daily; initiate with lower concentration if irritation is a concern. |
| Geriatric use | No specific dose adjustment; use age-appropriate formulation. Elderly may have increased risk of skin irritation; consider using lower concentration (0.05%) and monitor skin tolerance. |
| 1st trimester | Contraindicated. Tazarotene is teratogenic in animal studies. The product is classified as pregnancy category X by the FDA. Avoid use in women of childbearing potential unless contraception is used. |
| 2nd trimester | Contraindicated. No safe dose established; pregnancy category X. |
| 3rd trimester | Contraindicated. Avoid use due to potential risk of fetal harm. |
Clinical note
Comprehensive clinical and safety monograph for TAZORAC (TAZORAC).
| Placental transfer | Tazarotene and its active metabolite tazarotenic acid are lipophilic and may cross the placenta. Animal studies demonstrate fetal malformations after topical application, indicating systemic absorption and placental transfer. |
| Breastfeeding | It is not known if tazarotene is excreted in human milk. Due to the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. |
■ FDA Black Box Warning
Tazarotene is contraindicated in women who are or may become pregnant. Women of childbearing potential must have a negative pregnancy test within 2 weeks prior to starting therapy and use effective contraception. If pregnancy occurs, treatment should be discontinued immediately.
| Serious Effects |
PregnancyWomen of childbearing potential not using adequate contraceptionHypersensitivity to tazarotene or any component of the formulationEczematous skin
| Precautions | Avoid excessive exposure to UV light (sunlight, tanning lamps). Use with caution in patients with eczema or sunburned skin. Photosensitivity reactions may occur. Avoid contact with eyes, mouth, and mucous membranes. May cause skin irritation (e.g., redness, peeling, burning). Not recommended for use on intertriginous areas or with occlusive dressings. |
| Food/Dietary | No known food interactions. Tazarotene is applied topically and has negligible systemic absorption, so dietary restrictions are not required. |
Loading safety data…
| Lactation Rating | L4 (Possibly Hazardous) |
| Teratogenic Risk | Pregnancy Category X. First trimester: High risk of major fetal malformations including CNS, cardiovascular, and craniofacial defects. Second/third trimester: Continued teratogenicity; associated with increased risk of spontaneous abortion and preterm birth. |
| Fetal Monitoring | Pregnancy test before initiation, monthly during therapy, and 1 month after discontinuation. Use effective contraception during treatment and for 1 month after last dose. |
| Fertility Effects | No definitive human data; animal studies show no impairment of fertility at clinically relevant doses. |
| Clinical Pearls | TAZORAC (tazarotene) is a topical retinoid indicated for plaque psoriasis and acne vulgaris. Avoid application to eczematous or sunburned skin. Use with caution in patients with a history of hypersensitivity to retinoids. Combine with moisturizers to mitigate irritation. Advise strict photoprotection due to photosensitizing effects. Contraindicated in pregnancy (Category X); ensure negative pregnancy test before initiation in women of childbearing age. |
| Patient Advice | Apply a thin layer only to affected areas, avoiding eyes, mouth, and mucous membranes. · Wash hands immediately after application to prevent inadvertent transfer. · Use sunscreen daily and limit sun exposure; avoid tanning beds. · May cause redness, peeling, burning, or itching; these usually decrease with continued use. · Do not use if pregnant, planning to become pregnant, or breastfeeding. · Inform healthcare provider of all medications, especially other topical agents or photosensitizing drugs. · For acne, improvement may not be seen for 4–12 weeks; for psoriasis, improvement may take 2–12 weeks. |