Soritin

Approved Indications:

• Severe Psoriasis (including plaque, pustular, and erythrodermic types)
• Used in adult patients with severe, extensive, or disabling psoriasis unresponsive to other treatments.
• Often combined with phototherapy (PUVA or UVB) in resistant cases.
• Ichthyosis and Other Disorders of Keratinization
• Including congenital ichthyosis, pityriasis rubra pilaris, and Darier disease.

Important Off-label / Clinically Accepted Uses:

• Lichen planus (extensive, hypertrophic forms)
• Cutaneous lupus erythematosus
• Pityriasis rubra pilaris
• Chemoprevention of cutaneous squamous cell carcinoma in high-risk patients (e.g., organ transplant recipients)
• Palmoplantar keratoderma
• Severe acne (rarely used now, due to availability of isotretinoin)

Adults:

• Initial dose: 25–50 mg orally once daily with food or milk.
• Maintenance dose: 25–50 mg/day (adjusted based on response and tolerance).
• Duration varies; typically continued for several months with evaluation every 2–3 months.

Pediatrics:

• Not FDA-approved for pediatric use. However, off-label use has been reported in severe pediatric keratinization disorders.
• Dose typically adjusted to 0.5–1 mg/kg/day, under strict specialist supervision.

Elderly:

• Similar dosing as adults.
• Careful monitoring required due to increased sensitivity to mucocutaneous and hepatic side effects.

Renal Impairment:

• No formal dose adjustment guidelines; use with caution and monitor renal function.

Hepatic Impairment:

• Contraindicated in severe hepatic dysfunction.
• Use with caution in mild hepatic impairment with frequent liver function monitoring.

Administration Notes:

• Take with food or milk to enhance absorption.
• Do not consume alcohol during therapy and for 2 months after discontinuation (due to formation of etretinate, a long-acting and highly teratogenic metabolite).

Acitretin is a systemic retinoid (active metabolite of etretinate) that works by binding to nuclear retinoic acid receptors (RARs), particularly RAR-α, RAR-β, and RAR-γ. This binding regulates gene transcription involved in keratinocyte differentiation and proliferation. It normalizes epidermal cell growth, reduces hyperkeratinization, and suppresses inflammation. The therapeutic effects in psoriasis and keratinization disorders stem from its ability to reduce epidermal hyperplasia and restore normal skin architecture.

• Absorption: Oral bioavailability ~60% (enhanced with food or milk).
• Distribution: Highly lipophilic; extensively distributed in tissues. High plasma protein binding (>99%).
• Metabolism: Hepatic metabolism to inactive and active metabolites (including etretinate if combined with alcohol).
• Half-life:
• Acitretin: ~49 hours
• Etretinate (if formed): Up to 120 days
• Excretion: Primarily via feces (~60%) and urine (~40%).
• Note: Alcohol co-ingestion causes transesterification to etretinate, which has prolonged retention in adipose tissue and significantly extends teratogenic risk.

• Pregnancy Category: X
• Absolutely contraindicated in pregnancy due to severe teratogenicity.
• Must avoid pregnancy during treatment and for at least 3 years after discontinuation.
• Effective contraception (preferably two methods) is required during and for 3 years after use.
• Lactation:
• Contraindicated during breastfeeding. Acitretin is excreted in breast milk and may cause toxicity in infants.
• Caution: Acitretin should never be used in women of childbearing potential who are unwilling or unable to comply with strict pregnancy prevention programs.

• Primary Class: Retinoid
• Subclass: Second-generation synthetic aromatic retinoid (systemic)

• Pregnancy or likelihood of becoming pregnant
• Breastfeeding
• Severe hepatic or renal impairment
• Chronic abnormally elevated lipid levels
• Known hypersensitivity to acitretin or other retinoids
• Concurrent use of methotrexate or tetracyclines (risk of pseudotumor cerebri)

• Teratogenicity: Major boxed warning; women must use contraception for 3 years post-treatment.
• Hepatotoxicity: Monitor LFTs regularly. Discontinue if significant elevation occurs.
• Hyperlipidemia: Common; monitor serum triglycerides and cholesterol.
• Skeletal Toxicity: Long-term use may cause bone demineralization or hyperostosis.
• Mucocutaneous Effects: Dry skin, cheilitis, epistaxis, and conjunctivitis are common.
• CNS Effects: Risk of pseudotumor cerebri when combined with tetracyclines.
• Photosensitivity: Avoid excessive sun exposure and use sun protection.
• Psychiatric: Rare mood changes or depression may occur.

Common (≥10%)

• Skin and mucous membranes: Dry skin, peeling, scaling, pruritus, cheilitis
• Ocular: Dry eyes, conjunctivitis, decreased night vision
• Nail changes: Fragility, paronychia
• Lipid metabolism: Hypertriglyceridemia, hypercholesterolemia

Less Common

• Arthralgia, myalgia
• Elevated liver enzymes
• Hair thinning or loss
• Gastrointestinal upset

Serious/Rare

• Hepatitis, pancreatitis
• Skeletal hyperostosis, premature epiphyseal closure in children
• Depression, suicidal ideation
• Pseudotumor cerebri (especially with tetracyclines)

Onset: Most mucocutaneous symptoms begin within 1–2 weeks of initiation.
Dose-dependence: Many adverse effects are dose-related and may improve with dose reduction.

• Alcohol: Forms etretinate (prolonged teratogenicity).
• Tetracyclines: Risk of increased intracranial pressure.
• Methotrexate: Additive hepatotoxicity; contraindicated combination.
• Vitamin A / Other Retinoids: Increased toxicity risk; avoid concurrent use.
• Phenytoin: Possible altered metabolism.
• Hormonal contraceptives: No significant interaction, but hormonal methods must be used reliably.
• Enzymes involved: Primarily metabolized hepatically; CYP enzymes not significantly induced or inhibited.

• FDA & EMA: Reinforced the 3-year post-discontinuation contraception requirement in women.
• NICE (UK): Recognizes acitretin for use in severe chronic plaque psoriasis, especially where other treatments have failed.
• Updated monitoring guidelines: Recommend frequent lipid and liver function testing, especially in the first 2 months.
• New safety labeling: Stronger warnings added about psychiatric effects and teratogenicity.

• Store at 20°C to 25°C (68°F to 77°F).
• Protect from light and moisture.
• Keep in original packaging.
• Do not refrigerate or freeze.
• Keep out of reach of children.
• Follow handling precautions due to teratogenicity risk — wear gloves if crushed capsules are handled.