Isotretinoin capsules (Roaccutane)

Generic Name

Isotretinoin

Brand Names

Roaccutane

Accutane (formerly US)

Claravis

Absorica

Sotret

Isotroin

Oratane

May be available in soft gel or hard capsule form

Available Strengths

10 mg

20 mg

30 mg

40 mg

Available as lipid-based or micronized formulations for improved absorption

Drug Class

Retinoid (oral)

Vitamin A derivative (13-cis-retinoic acid)

Keratolytic and sebo-suppressive agent

Mechanism of Action

Isotretinoin targets all major pathogenic factors of acne

– Decreases sebaceous gland size and sebum production

– Normalizes follicular keratinization, preventing comedone formation

– Inhibits growth of Cutibacterium acnes

– Exerts anti-inflammatory effects via neutrophil and cytokine modulation

Acts primarily through activation of retinoic acid receptors (RARs), modulating gene transcription for epidermal differentiation and sebaceous gland activity

Indications

Severe nodular or cystic acne unresponsive to conventional therapies

Acne conglobata

Acne with risk of scarring or psychological impact

Moderate acne unresponsive to oral antibiotics and topical agents (off-label)

Gram-negative folliculitis

Rosacea (refractory cases, off-label)

Hidradenitis suppurativa (off-label)

Seborrheic dermatitis (off-label, limited use)

Ichthyosis and other keratinization disorders

Off-label Uses

Scalp folliculitis

Lichen spinulosus

Neuroblastoma (adjunct therapy)

Skin cancers (chemoprevention in xeroderma pigmentosum)

Dosage and Administration

Standard Adult Dosing

Initial dose: 0.5 mg/kg/day in divided doses for 2–4 weeks

Increase to 1 mg/kg/day as tolerated

Duration: 15–20 weeks or until cumulative dose of 120–150 mg/kg is reached

Course may be repeated after ≥8 weeks if relapse occurs

Pediatric Use

Approved for patients ≥12 years with severe acne

Dosing based on weight

Same cumulative dose targets as adults

Administration Advice

Take with high-fat meal to enhance absorption

Micronized/lipid-based formulations (e.g., Absorica) may be taken without food

Swallow whole capsules; do not crush or chew

Pharmacokinetics

Absorption enhanced with dietary fat

Highly protein-bound (>99%)

Metabolized in the liver to active and inactive metabolites

Half-life: ~10–20 hours for isotretinoin

Eliminated primarily in feces and urine

Contraindications

Pregnancy (absolute)

Women planning pregnancy

Hypersensitivity to isotretinoin or retinoids

Severe hepatic impairment

Hypervitaminosis A

Concomitant use of tetracyclines (risk of pseudotumor cerebri)

Breastfeeding

Warnings and Precautions

Pregnancy (Category X)

Isotretinoin is a potent teratogen

Causes severe, life-threatening birth defects

Absolute contraindication in pregnancy

Requires strict adherence to Pregnancy Prevention Programs (e.g., iPLEDGE in the US)

Mandatory use of two forms of contraception

Pregnancy tests required before, during, and after treatment

Psychiatric Effects

Depression, mood changes, suicidal ideation, psychosis

Screen for history of mental health disorders

Monitor mood closely during treatment

Discontinue if severe psychiatric symptoms occur

Ocular Effects

Dry eyes, conjunctivitis, corneal opacities, visual disturbances

Decreased night vision (may be irreversible)

Avoid refractive eye surgery during and for 6 months after treatment

Skeletal Effects

Premature epiphyseal closure (rare, high dose, pediatric use)

Diffuse idiopathic skeletal hyperostosis

Arthralgia, myalgia

Lipid Abnormalities

Hypertriglyceridemia, hypercholesterolemia

Monitor fasting lipids before and during therapy

Hepatic Effects

Elevated transaminases (AST, ALT)

Baseline and periodic LFTs required

Dermatologic Reactions

Dry skin, cheilitis (nearly universal), peeling, rash, pruritus

Photosensitivity

Skin fragility: avoid waxing and dermabrasion during and for 6 months after therapy

Gastrointestinal

IBD (controversial association)

Pancreatitis (especially if triglycerides >800 mg/dL)

Other

Benign intracranial hypertension (pseudotumor cerebri)

May be increased with tetracyclines or corticosteroids

Bone demineralization with long-term or repeated use

Adverse Effects

Very Common (≥10%)

Dry lips (cheilitis)

Dry skin, nose, and eyes

Nosebleeds (epistaxis)

Conjunctivitis

Elevated lipids

Back pain, arthralgia

Headache

Photosensitivity

Common (1–10%)

Depression, irritability

Elevated liver enzymes

Hair thinning

Visual disturbances

Menstrual irregularities

Rare (<1%)

Psychosis

Suicidal ideation

Alopecia (permanent)

Pancreatitis

Hearing loss

Corneal opacity

Severe allergic reaction

IBD-like symptoms

Drug Interactions

Vitamin A supplements

Additive toxicity

Avoid concurrent use

Tetracyclines

Increased risk of intracranial hypertension

Contraindicated

Oral contraceptives

Isotretinoin may decrease effectiveness of low-dose contraceptives

Use two reliable forms of contraception

Ethinylestradiol + norgestimate or desogestrel combinations preferred

Corticosteroids

Additive risk of bone demineralization

Phenytoin

May exacerbate bone toxicity

Alcohol

Increased risk of liver toxicity and hypertriglyceridemia

Monitoring Parameters

Mandatory Baseline Tests

Pregnancy test (within 1 week before starting)

Liver function tests (AST, ALT)

Fasting lipid profile (triglycerides, cholesterol)

CBC (optional)

Monitoring Schedule

Pregnancy test: monthly

LFTs and lipids: monthly or every 4–6 weeks

Mood and psychiatric symptoms: throughout treatment

Vision changes: monitor and refer if persistent

Contraceptive Monitoring

Two negative pregnancy tests before starting

Continue contraception 1 month after discontinuation

Post-treatment Washout Period

Avoid pregnancy for 1 month after last dose

Avoid blood donation during and 1 month post-therapy

Pregnancy and Lactation

Pregnancy

Absolute contraindication

Causes severe fetal abnormalities

Requires enrollment in pregnancy prevention programs

Lactation

Excreted in breast milk

Not recommended during breastfeeding

Legal and Regulatory Status

Prescription-only, controlled dispensing

Subject to iPLEDGE in the US

Banned for over-the-counter sale

Listed in WHO Essential Medicines for severe acne

Special Counseling Points

Inform all patients of teratogenic risks

Provide iPLEDGE documentation and consent forms

Avoid alcohol, waxing, laser procedures

Use non-comedogenic moisturizers, lip balm, eye lubricants

Report symptoms of depression, abdominal pain, or visual changes immediately

Comparative Notes

Isotretinoin vs Oral Antibiotics

Isotretinoin is more effective and curative

Used when antibiotics fail or for severe nodular acne

Isotretinoin vs Topical Retinoids

Oral form used for severe cases

Topical retinoids better for mild-moderate acne

Isotretinoin vs Hormonal Therapies (e.g., oral contraceptives, spironolactone)

Hormonal agents preferred for women with androgenic acne or PCOS

Isotretinoin used when hormonal therapy fails or in males