Tretinoin

• Acne Vulgaris:
  Treatment of mild to moderate acne, particularly comedonal acne and inflammatory lesions.
• Photodamaged Skin:
  Used to reduce fine wrinkles, mottled hyperpigmentation, and tactile roughness associated with chronic sun damage.
• Acute Promyelocytic Leukemia (APL):
  Indicated in combination therapy for induction and maintenance of remission in APL patients positive for the t(15;17) translocation.
• Off-label Uses:
• Keratosis pilaris
• Other disorders of keratinization
• Some skin cancers or precancerous lesions in topical formulations

• Topical Formulations:
• Acne: Apply a thin layer once daily in the evening on affected areas; typical concentrations range from 0.01% to 0.1%.
• Photodamage: Apply once daily, typically at concentrations of 0.025% to 0.1%.
• Oral Formulations (for APL):
• Adults and children: 45 mg/m²/day in two divided doses until remission, usually 90 days or as directed by hematologist.
• Special Populations:
• Pediatrics: Use topical tretinoin with caution; oral therapy only under specialist care for APL.
• Elderly: No specific dose adjustments; monitor skin tolerance.
• Hepatic/Renal Impairment: Use oral tretinoin cautiously; topical use generally safe.
• Administration Notes:
• For topical use, wash the skin gently before application; avoid contact with eyes, lips, and mucous membranes.
• For oral use, administer with food to reduce gastrointestinal upset.

Tretinoin, a retinoid and active metabolite of vitamin A, modulates gene expression by binding to nuclear retinoic acid receptors (RARs) in skin cells and leukemic promyelocytes. In skin, tretinoin normalizes desquamation by promoting epidermal cell turnover, reducing follicular occlusion, and exerting anti-inflammatory effects, leading to improvement in acne and photodamaged skin. In APL, tretinoin induces differentiation of abnormal promyelocytes into mature granulocytes, thereby restoring normal hematopoiesis and inducing remission.

• Absorption:
• Topical: Minimal systemic absorption; varies by formulation and skin condition.
• Oral: Rapid absorption with peak plasma concentrations reached in 1–2 hours.
• Distribution: Highly protein-bound (>95%) in plasma.
• Metabolism: Extensive hepatic metabolism primarily via cytochrome P450 enzymes into less active metabolites.
• Half-life: Approximately 0.5–2 hours after oral administration.
• Excretion: Mainly via urine as metabolites; small amounts in feces.

• Pregnancy: Category C for topical use and Category D for oral use (APL treatment). Oral tretinoin is teratogenic and contraindicated during pregnancy. Topical use should be avoided during pregnancy unless benefits outweigh risks.
• Lactation: Unknown if excreted in human milk; breastfeeding is generally not recommended during oral tretinoin therapy. Caution advised for topical use.

• Retinoid
• Vitamin A derivative
• Antineoplastic agent (oral formulation for APL)

• Hypersensitivity to tretinoin or any component of the formulation.
• Pregnancy (oral use contraindicated; topical use with caution).
• Use with concomitant photosensitizing agents or products causing skin irritation (topical).
• Severe hepatic impairment (oral).

• Topical Use:
• May cause skin irritation, erythema, peeling, dryness, and photosensitivity. Use sunscreen and avoid excessive sun exposure.
• Avoid application to broken or eczematous skin.
• Oral Use:
• Monitor for differentiation syndrome, a potentially life-threatening complication in APL patients.
• Hepatotoxicity, hyperlipidemia, and leukocytosis may occur; monitor liver function tests and blood counts.
• General:
• Avoid use with other topical acne treatments unless directed.
• Use cautiously in patients with pre-existing skin disorders.

• Topical:
• Common: Erythema, dryness, peeling, burning sensation, pruritus.
• Rare: Photosensitivity reactions, contact dermatitis.
• Oral:
• Common: Headache, fever, weakness, dry skin, hyperlipidemia.
• Serious: Differentiation syndrome, hepatotoxicity, leukocytosis, pseudotumor cerebri (rare).

• Increased skin irritation with concurrent use of other topical agents such as benzoyl peroxide, salicylic acid, or corticosteroids.
• Oral tretinoin metabolism may be affected by CYP3A4 inhibitors or inducers, altering plasma levels and toxicity risk.
• Avoid concurrent use with tetracyclines due to risk of pseudotumor cerebri.

• Updated guidelines emphasize sun protection during topical tretinoin therapy to minimize photosensitivity.
• Oral tretinoin remains a cornerstone in APL management with improved survival outcomes.
• Newer formulations with improved tolerability profiles are available for topical use.
• Monitoring for differentiation syndrome and lipid abnormalities is standard during oral therapy.

• Store at 20°C to 25°C (68°F to 77°F), protected from light and moisture.
• Keep topical formulations tightly closed and away from heat.
• Oral capsules should be stored in original packaging to protect from light.
• Avoid freezing.