Mechanism of action
- Tazarotenic acid also binds to RAR-γ and RAR-β , but not to RXR.
- By binding to the various RAR, tazarotenic acid modulates the expression of retinoid-responsive genes, including those that regulate cell proliferation, cell differentiation, and inflammation.
- Blocks induction of ornithine decarboxylase activity with decreased cell proliferation and hyperplasia.
- Suppresses MRP8 (a marker of inflammation in psoriasis), involucrin, keratinocytes glutaminase, elafn, keratin 6 &16.
- suppression of activation of the activator protein 1, which results in reduced expression of several matrix metalloproteinases from keratinocytes.
- Decreases expression of Toll-like receptor (TLR) 2 .
- Inhibits cornifed envelope formation and corneocyte accumulation in Rhino mouse skin.
- Inhibits cross-linked cornifed envelope formation.
- Downregulates expression of the epidermal growth factor receptor.
Indications
- Acne vulgaris.
- Psoriasis, <20% of body surface area.
- Photoaging .
- Acanthosis nigricans.
- Confluent and reticulated papillomatosis.
- Cutaneous t-cell lymphoma, patch/plaque.
- Darier’s disease.
- Elastosis perforans serpiginosa.
- Follicular dyskeratosis.
- Ichthyoses, congenital.
- Keratoderma blenorrhagicum.
- Keratosis pilaris.
- Lichen planus, oral.
- lupus, discoid.
- Spiny keratoderma.
- Warty dyskeratoma.
- Viral-associated trichodysplasia .
- Warts.
- Erythrokeratodermia variabilis (mild).
Dosage
- A pea-sized amount may be applied to the affected area once daily at night.
Monitoring
- Pregnancy testing : for females of reproductive potential within 2 weeks prior to initiating therapy.
Side effects
- Irritation .
- Erythema .
- Desquamation .
- Pruritus .
- Burning.
- Worsening of psoriasis.
- Photosensitivity.
- Dry skin.
- Fissuring, bleeding.
- Teratogenic precautions.
Contraindications
- Hypersensitivity to drug/class.
- Pregnancy.
- Unstable plaque psoriasis in a phase of progression.
- Erythrodermic psoriasis.
Interactions
- Dermatologic medications and cosmetics that have a strong drying effect should be avoided.
- Increased photosensitivity: photosensitizers ( thiazides, tetracyclines, fluoroquinolones, phenothiazines, sulfonamides).
Pregnancy &Lactation
- Pregnancy categoy X : Not to be used in pregnant women.
- Topical tazarotene has not been studied during breastfeeding.
- Tazarotene is not contraindicated during breastfeeding and if tazarotene is required by the mother, it is not a reason to discontinue breastfeeding.
- Some experts feel it should not be used on greater than 20% of the body surface area because of possible absorption.
- If tazarotene is used, ensure that the infant’s skin does not come into direct contact with the areas of maternal skin that have been treated and the infant does not ingest the product from the mother’s skin.
Precautions
- Obtain a pregnancy test in females of reproductive potential within 2 weeks prior to initiating treatment.
- Advise females of reproductive potential to use effective contraception.
- Avoid use on eczematous skin, as such use may cause severe irritation.
- Local tolerability reactions and hypersensitivity adverse reactions have been observed with topical tazarotene, including blistering, skin desquamation, and urticaria; if adverse reactions occur, discontinue medication until integrity of skin is restored,or reduce dosing to an interval the patient can tolerate.
- Ask patients if they are using other drugs that could potentially increase sunlight sensitivity.
- Use of sunscreens (minimum strength of SPF 15) & protective clothing recommended during use.
- Not for use in lentigo maligna.
Drug Info
- Tazarotene is a prodrug that is rapidly hydrolyzed in tissues to the active metabolite termed tazarotenic acid.
- Tazarotenic acid has a high affnity to the RAR-γ nuclear receptor that is the predominant receptor present in the epidermis.
- Tazarotene foam 0.1% was FDA-approved in 2012 for the treatment of acne vulgaris in patients 12 years old and over.