What is the recommended treatment protocol for Acitretin (Soriatane) in patients with severe psoriasis?

Acitretin Treatment Protocol for Severe Psoriasis

Start acitretin at 25-30 mg once daily with food or milk for 2-4 weeks, then titrate to a maintenance dose of 25-50 mg daily based on clinical response and tolerability, with optimal therapeutic results typically achieved after 6-8 weeks and peak response requiring 3-6 months. 1

Dosing Strategy

Initial Dosing

• Begin with 25-30 mg once daily taken with meals or milk to allow gradual onset of tolerance to side effects 1
• Continue this initial dose for 2-4 weeks before considering dose adjustment 1
• Gradual dose escalation is the most effective approach and minimizes adverse effects 1

Maintenance Dosing

• Target maintenance dose: 25-50 mg daily for 6-8 weeks to achieve optimal therapeutic results 1
• The effective dose range is 10-50 mg daily, with some patients requiring up to 75 mg daily maximum 1
• Balance efficacy against individual patient tolerability—this is the major element in acitretin dosing 1
• Evidence suggests 35 mg daily may be the optimal dose, achieving 76% PASI reduction with better tolerability than 50 mg daily 2

Response Timeline

• Satisfactory therapeutic results may appear within 2-4 weeks at initial dosing 1
• Response is gradual and typically requires 3-6 months to reach peak effect 1
• Therapy can be discontinued once lesions have improved sufficiently; relapses should be treated with the same protocol 1

Specific Psoriasis Variants

Severe Variants (Pustular, Erythrodermic, Palmoplantar)

• Acitretin is particularly effective for pustular psoriasis, with 84% of patients showing improvement 1
• Response in pustular psoriasis (both generalized and palmoplantar) can be quite rapid and remarkable 1
• Effective for hyperkeratotic (plaque-type) palmoplantar psoriasis as monotherapy or combination therapy 1

Pediatric Dosing

• For children with severe pustular psoriasis: 0.1-1 mg/kg/day, with response typically seen within 3 weeks 3
• Avoid in female adolescents approaching childbearing potential due to 3-year teratogenic risk 3, 4

Combination Therapy Protocols

With Phototherapy (Preferred Strategy)

• Begin with 2 weeks of acitretin monotherapy, then add UVB phototherapy 1
• Reduce initial UVB dose by 30-50% for the first week due to increased susceptibility to UVB-induced erythema, then gradually increase as tolerated 1
• Acitretin 25 mg daily plus phototherapy equals the efficacy of acitretin 35 mg daily monotherapy 1
• Combination therapy with acitretin 50 mg daily plus BB-UVB achieved 74% improvement vs. 42% with acitretin alone and 35% with BB-UVB alone 1

With PUVA

• Add acitretin to failing PUVA regimens while simultaneously reducing UVA dose 1
• Combination reduces photochemotherapy sessions needed and cumulative UVA dosage 1
• Critical advantage: acitretin combined with PUVA decreases cutaneous squamous cell carcinoma incidence compared to PUVA alone 1

Mandatory Monitoring Protocol

Baseline Requirements

• Comprehensive history and physical examination 1
• Lipid profile (fasting cholesterol and triglycerides) 1
• Complete blood count (CBC) 1
• Liver function tests (LFTs) 1
• Renal function tests 1
• Pregnancy test in all women of childbearing potential 1

Ongoing Monitoring Schedule

• Fasting lipids: every 2-4 weeks for first 2 months, then every 3 months 1
• LFTs: monthly for first 3 months, then every 3 months 1
• CBC and renal function: every 3 months 1
• Blood sugar levels in diabetic patients at similar intervals, with more frequent capillary glucose checks during first few weeks 1

Action Thresholds for Lipid Abnormalities

• Triglycerides >5 mmol/L: Refer to lipidologist and investigate other causes (alcohol, SLE, diabetes, hypothyroidism, renal/hepatic problems, hormonal dysfunction) 1
• Triglycerides approaching or >10 mmol/L: Discontinue acitretin immediately and urgently refer to lipidologist due to acute pancreatitis risk 1
• For persistently elevated lipids with good therapeutic response: introduce dietary measures before considering lipid-lowering drugs 1

Skeletal Monitoring

• Routine radiological investigation is NOT recommended due to radiation exposure risk, unpredictable ossification sites, and high false-positive rate in normal individuals 1
• Obtain targeted X-rays only if patients become symptomatic 1

Critical Contraindications and Safety Warnings

Absolute Contraindications

• Pregnancy or intent to become pregnant within 3 years after discontinuation 1, 5
• Nursing mothers 1
• Severely impaired liver or kidney function 1
• Chronic abnormally elevated blood lipid values 1

Teratogenicity Management (Most Important Safety Concern)

• Acitretin is a potent teratogen causing multiple malformations, particularly if used between weeks 3-6 of gestation (skeletal, craniofacial, CNS, auditory, ocular, cardiovascular abnormalities) 1
• Contraception must be maintained for 3 YEARS after therapy completion, not 2 months as previously recommended 1
• This extended period is necessary because acitretin undergoes spontaneous transformation into etretinate (half-life 168 days vs. acitretin's 49 hours) 1
• Alcohol ingestion promotes conversion of acitretin to etretinate; the actual amount of alcohol necessary is unknown, so unintentional exposure to alcohol-containing items may pose risk 1
• Acitretin is NOT a teratogen when used by male patients fathering an infant 1

Common Adverse Effects (Dose-Dependent)

• Mucocutaneous effects occur in nearly all patients: cheilitis, drying of mucous membranes (eyes, nose, lips), xerosis, xerophthalmia 1, 6
• Alopecia (frequency and severity depend on dose and duration) 1, 6
• Desquamation, pruritus, "sticky" skin, paronychia 1
• Paresthesia, headache, pseudotumor cerebri (rare) 1
• Nausea, abdominal pain 1
• Joint pain, myalgia 1
• Hypertriglyceridemia (35% at 50 mg/day) 1, 7
• Abnormal LFTs 1

Drug Interactions

• Avoid concurrent tetracyclines (both increase intracranial pressure) 1
• Avoid concurrent vitamin A and other oral retinoids 1
• May interfere with microdosed progestin contraceptive effect 1
• May reduce protein binding of phenytoin 1
• Combine with methotrexate cautiously due to additive hepatotoxicity risk 1
• May interact with glucose-lowering effect of glibenclamide 1

Clinical Efficacy Data

Monotherapy Results

• At 50 mg daily: statistically significant improvements in physician's global evaluation and severity ratings (scaling, thickness, erythema) at 8 weeks 5
• After 24 weeks: all efficacy variables significantly improved from baseline (P ≤ 0.01) 5
• Good to excellent (≥50%) clearance achieved in >75% of patients with severe psoriasis 7
• Doses of 10-25 mg daily do NOT achieve statistically significant improvement over placebo 8, 6
• 50 mg and 75 mg daily dosages are statistically significantly better than placebo 8, 6

Relapse Pattern

• Most patients experience relapse after discontinuing therapy 5
• Most patients require retreatment after approximately 3 months without acitretin 8
• Subsequent 24-week courses are generally effective and well tolerated 8

Special Populations

Women of Childbearing Potential

• Reserve acitretin for non-pregnant patients unresponsive to other therapies or whose clinical condition contraindicates other treatments 5
• Acitretin therapy should not be used where there is a suitable alternative 1
• Where used, contraception must be discussed and undertaken for 3 years 1

Elderly Patients

• Use with caution 1

Patients with Immunodeficiency

• Use with caution 1

Common Pitfalls to Avoid

• Do not start at high doses (50-75 mg) without gradual escalation—this increases adverse effects without improving long-term outcomes 1
• Do not combine with PUVA without reducing UVA dose—acitretin increases photosensitivity 1
• Do not add UVB to acitretin without reducing UVB dose by 30-50% initially—risk of severe erythema 1
• Do not ignore triglyceride levels >10 mmol/L—this is an emergency requiring immediate discontinuation 1
• Do not prescribe to women of childbearing potential without documenting 3-year contraception plan 1
• Do not perform routine skeletal X-rays—only obtain if symptomatic 1