What is the recommended starting dose, titration schedule, monitoring, and safety considerations for acitretin in an adult with psoriasis?

Acitretin Dosing for Adult Psoriasis

Start acitretin at 25-30 mg once daily with food for 2-4 weeks, then titrate to a maintenance dose of 25-50 mg daily based on therapeutic response and tolerability, with a maximum of 75 mg daily if needed. 1

Starting Dose and Administration

• Initial dose: 25-30 mg once daily taken with meals or milk for 2-4 weeks 1
• Gradual dose escalation is the most effective approach, allowing gradual onset of tolerance to side effects 1
• The capsules must be taken with food or milk to optimize absorption 1

Titration Schedule

• After the initial 2-4 weeks, adjust to maintenance dose of 25-50 mg daily for an additional 6-8 weeks to achieve optimal therapeutic results 1
• Maximum dose: 75 mg daily may be necessary in some cases 1
• Lower doses (≤25 mg/day) are often used to minimize adverse effects, especially in combination regimens with phototherapy 1
• Response is gradual and typically requires 3-6 months to reach peak effect 1

Dose-Response Evidence

A key randomized controlled trial found that 35 mg/day was more efficacious than both 25 mg/day and 50 mg/day, achieving PASI 75 in 69% of patients versus 47% and 53% respectively, with a better safety profile than the 50 mg dose 2. However, the established guidelines recommend the broader 25-50 mg range, as individual variation in absorption and metabolism is substantial 1.

Baseline Monitoring Requirements

Before initiating therapy, obtain: 1

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

Ongoing Monitoring Schedule

First 2 Months (Intensive Phase)

• LFTs and lipid profile: every 2-4 weeks 1
• If abnormal results obtained, institute weekly checks and adjust dose accordingly 1

After 2 Months (Maintenance Phase)

• LFTs and lipid profile: every 3 months 1
• CBC and renal function tests: every 3 months 1
• Pregnancy test if indicated: every 3 months 1

Special Monitoring for Diabetic Patients

• Blood sugar levels should be monitored at similar intervals 1
• Patients should check capillary glucose more frequently than usual during the first few weeks of treatment 1

Critical Safety Thresholds and Actions

Hepatotoxicity Management

• Discontinue acitretin if transaminases are elevated to 3 times their upper normal limit 1
• Refer to gastroenterology if bilirubin >50 µmol/L or ALT >200 IU/L 1
• Continue monitoring hepatic function for at least 3 months after discontinuation 1
• In severe disease where all else has failed, therapy could be continued in consultation with a gastroenterologist and would require liver biopsy 1

Lipid Abnormalities

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

Absolute Contraindications

• Pregnancy - multiple malformations can occur, particularly if used between weeks 3-6 of gestation 1
• Women of childbearing potential must use effective contraception for 3 years after discontinuation (not 2 months as previously recommended, due to detection of etretinate formation) 1, 3
• Severely impaired liver or kidney function 1, 4
• Chronic abnormally elevated blood lipid values 1
• Concurrent use with tetracyclines (risk of pseudotumor cerebri) 1

Common Pitfalls and How to Avoid Them

Starting Too High

• Doses of 50-75 mg daily are effective but cause more mucocutaneous side effects 5, 6
• Starting at 25-30 mg allows tolerance development and is better tolerated 1

Inadequate Contraception Counseling

• The conversion of acitretin to etretinate (which has a 120-day half-life) can occur, especially with alcohol consumption 1, 3
• The contraception period was extended from 2 months to 3 years based on this finding 1

Premature Discontinuation

• Patients and providers may become discouraged before the 3-6 month timeframe needed for peak response 1
• Set appropriate expectations at initiation

Missing Lipid Monitoring

• Hypertriglyceridemia occurs in approximately 35% of patients on 50 mg/day 3, 6
• Elevation in transaminases occurs in 13-16% of patients 1
• Early detection through proper monitoring prevents serious complications like pancreatitis 1

Combination Therapy Considerations

When combining acitretin with phototherapy: 1

• Reduce UVB dose by 30-50% initially due to increased susceptibility to UVB-induced erythema
• Begin with 2 weeks of acitretin monotherapy, then add phototherapy
• Lower acitretin doses (25 mg/day) can be as effective as higher monotherapy doses (35 mg/day) when combined with phototherapy 1

Drug Interactions to Avoid

• Vitamin A supplementation - increases risk of hypervitaminosis A 1
• Tetracyclines - both increase intracranial pressure 1
• Glyburide (glibenclamide) - acitretin may interact with glucose-lowering effect 1
• Alcohol - can lead to formation of etretinate, extending teratogenic risk 1
• Methotrexate - both cause hepatotoxicity; combine with caution 1

Unique Advantage Over Other Systemic Therapies

Acitretin is not immunosuppressive, making it safe for continued use during active infections, unlike most other systemic psoriasis treatments 1, 4. This is particularly valuable in patients with recurrent infections or those at high infection risk.