What is the recommended starting dose of acitretin for an adult with severe plaque psoriasis?

Recommended Starting Dose of Acitretin for Severe Plaque Psoriasis

For adults with severe plaque psoriasis, initiate acitretin at 25–50 mg once daily with the main meal, then adjust to a maintenance dose of 25–50 mg daily based on individual response and tolerability. 1

Initial Dosing Strategy

The FDA-approved dosing range is 10–50 mg daily as a single dose, with therapy typically initiated at 25–50 mg per day taken with the main meal to optimize absorption. 2, 1

Evidence-Based Starting Approaches:

Option 1: Standard initiation (25–50 mg/day)

• The FDA label and AAD guidelines recommend starting at 25–50 mg daily for most patients with severe plaque psoriasis. 2, 1
• This approach balances efficacy with tolerability, as higher doses increase mucocutaneous side effects. 2

Option 2: Low-dose escalation (preferred for minimizing side effects)

• Begin with 25–30 mg once daily for 2–4 weeks, then gradually escalate to 25–50 mg daily for 6–8 weeks to reach optimal therapeutic response. 3
• This strategy is particularly useful when combining with phototherapy or in patients concerned about tolerability. 2, 3
• Lower doses (≤25 mg/day) are specifically recommended when acitretin is combined with UV therapy to minimize adverse effects. 2

Dose-Response Relationship

The most recent high-quality randomized controlled trial (2013) comparing fixed doses found that 35 mg daily achieved superior efficacy (76% PASI reduction, 69% achieving PASI 75) compared to both 25 mg (54% reduction, 47% PASI 75) and 50 mg daily (54% reduction, 53% PASI 75) after 12 weeks. 4 Importantly, the 35 mg dose had a better safety profile than 50 mg, with fewer dose-dependent mucocutaneous side effects. 4

However, acitretin monotherapy is generally less effective than other systemic agents for plaque psoriasis, with only 23% achieving PASI 75 at 50 mg/day over 8 weeks in earlier trials. 2 Efficacy is substantially enhanced when combined with phototherapy. 2

Maintenance and Dose Adjustments

• Maintenance doses of 25–50 mg daily are typically sufficient once initial response is achieved. 2, 1
• Maximum dose of 75 mg daily may be required in refractory cases, but this significantly increases mucocutaneous side effects. 3
• Clinical response is gradual, requiring 3–6 months to reach peak efficacy, so set patient expectations accordingly. 3
• After 6–12 months of continuous treatment, 75–88% of patients with chronic plaque psoriasis can maintain PASI 50. 2

Special Considerations for Combination Therapy

When adding acitretin to phototherapy:

• Reduce UVB dose by 30–50% at initiation to limit erythema risk. 2, 3
• Begin with 2 weeks of acitretin monotherapy before introducing phototherapy. 3
• 25 mg daily acitretin combined with phototherapy can achieve efficacy comparable to 35 mg monotherapy. 3
• Combination therapy reduces time to clearance and total radiation exposure. 2, 5

Critical Safety Monitoring

Baseline Assessment (before starting):

• Comprehensive history and physical examination 2, 3
• Fasting lipid profile (cholesterol and triglycerides) 2, 3
• Complete blood count (CBC) 2, 3
• Liver function tests (LFTs) 2, 3
• Renal function (creatinine, eGFR) 2, 3
• Pregnancy test in all women of childbearing potential 2, 3

Ongoing Monitoring:

• First 8 weeks: LFTs and lipid profile every 2 weeks 2
• After 8 weeks: LFTs and lipid profile every 6–12 weeks (or every 3 months per more recent guidance) 2, 3
• CBC and renal function every 3 months 2, 3
• Pregnancy testing every 3 months when indicated 3

Absolute Contraindications

Acitretin is strictly contraindicated in:

• Pregnancy – potent teratogen causing multiple malformations, especially weeks 3–6 of gestation 2, 3
• Women of childbearing potential without effective contraception for 3 years after stopping (due to possible conversion to etretinate with alcohol) 3, 5
• Severely impaired liver or kidney function 2, 3
• Chronically elevated blood lipids 2, 3
• Concurrent tetracycline use (risk of pseudotumor cerebri) 2, 3

Common Pitfalls to Avoid

• Do not combine with alcohol – promotes conversion to etretinate, extending teratogenic potential from months to years. 3, 5
• Do not combine with methotrexate without extreme caution – both cause hepatotoxicity. 2, 3
• Do not use with vitamin A supplements – increases hypervitaminosis A risk. 2, 3
• Do not expect rapid results – unlike pustular psoriasis (which responds in 3 weeks), plaque psoriasis requires 2–3 months for meaningful improvement. 2, 6
• Dispense only monthly supplies with Medication Guide each time, as required by FDA. 1

Clinical Advantage

Unlike most systemic psoriasis agents, acitretin is non-immunosuppressive, allowing safe continuation during active infections. 3 This makes it particularly valuable in patients with recurrent infections or immunocompromise concerns.