Tretinoin

Retinoid, Topical retinoid, Antineoplastic (oral, APL)

Tretinoin (all-trans retinoic acid, ATRA)

Retin-A, Renova, Atralin, Avita, Tretin-X, Refissa, Altreno; Vesanoid (oral, APL)

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Titration strategies

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Effects

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Summary

Classes

Retinoid, Topical retinoid, Antineoplastic (oral, APL)

Pharmacy

Starting dose

Topical: pea-sized amount to dry face at bedtime, building from 2-3×/week to nightly as tolerated; oral APL: 45 mg/m²/d in divided doses

Preparations

Topical 0.01-0.1% creams, gels, micropsheres, lotions; oral 10 mg capsules (Vesanoid)

US FDA Max

Topical: nightly; oral APL: 45 mg/m²/d

Pharmacology

Routes

Topical, oral (APL only)

Onset

Topical: irritation within days; acne improvement 6-12 weeks; oral APL response within days

Duration

N/A

Half-life

~0.5-2 hours (oral)

Bioavailability

Topical: minimal systemic absorption with normal skin; oral: variable, induced metabolism with repeated dosing

Pregnancy

Oral tretinoin is teratogenic (Category D historically; APL exception treated under strict pregnancy avoidance); topical tretinoin in pregnancy has lower (but not zero) concern and is generally avoided.^{[citation needed]}

Legal status

Rx-only in US

Purported mechanism

Tretinoin is all-trans retinoic acid, the active metabolite of vitamin A; it binds nuclear retinoic acid receptors (RAR α/β/γ), regulating transcription of genes governing epithelial differentiation, proliferation, and inflammation.▲0▼ In acne, normalizes follicular keratinization and reduces comedone formation. In APL, the PML-RARα fusion oncoprotein responds to pharmacologic ATRA by resuming terminal granulocytic differentiation — one of the first successful examples of differentiation therapy in oncology, transforming APL from highly fatal to highly curable. Differentiation syndrome (capillary leak, hyperleukocytosis, dyspnea) is the major adverse effect of oral APL induction.