Overview
Isotretinoin is a retinoid medication primarily used for severe, recalcitrant nodular acne that has not responded to conventional therapy. It is a vitamin A derivative that reduces sebum production, normalizes keratinization, and has anti-inflammatory effects. Due to its teratogenic potential, it requires strict risk management programs.
Mechanism of Action
Isotretinoin is a retinoid that binds to nuclear retinoic acid receptors (RARs), modulating gene transcription. It reduces sebaceous gland size and sebum production (up to 90%), normalizes follicular keratinization, decreases Cutibacterium acnes colonization, and has anti-inflammatory properties through inhibition of chemotactic responses.
Indications
- Severe recalcitrant nodular acne unresponsive to conventional therapy
- Moderate acne with scarring or psychological distress
- Other dermatological conditions (off-label): rosacea, hidradenitis suppurativa, certain keratinization disorders
Dosage
Initial: 0.5-1 mg/kg/day in 2 divided doses. Maintenance: 0.5-2 mg/kg/day. Total cumulative dose: 120-150 mg/kg over 15-20 weeks. Maximum: 2 mg/kg/day. Should be taken with food to enhance absorption.
Black Box Warning
BOXED WARNING: Teratogenicity - causes severe birth defects. Requires pregnancy prevention program (iPLEDGE in US)
Contraindications
- Pregnancy, planning pregnancy, or breastfeeding
- Hypersensitivity to isotretinoin or parabens
- Concurrent tetracycline antibiotic use
- Severe hepatic impairment
- Hypervitaminosis A
- Patients with significantly elevated serum triglycerides
Side Effects
- Common: dry skin/lips/eyes/nose (cheilitis), epistaxis, conjunctivitis, arthralgias, myalgias, headache
- Serious: teratogenicity, depression/suicidal ideation, pseudotumor cerebri, pancreatitis, hepatitis, inflammatory bowel disease, severe skin reactions
- Laboratory abnormalities: elevated triglycerides, cholesterol, liver enzymes; decreased HDL
Interactions
- Tetracyclines: increased risk of pseudotumor cerebri
- Vitamin A supplements: additive toxicity
- Alcohol: may increase triglyceride levels
- Phenytoin: potential increased toxicity
- Corticosteroids: may increase intracranial pressure
- St. John's Wort: may reduce contraceptive effectiveness