Apremilast Dosing for Moderate-to-Severe Plaque Psoriasis
Apremilast requires a mandatory 5-day titration starting at 10 mg daily on Day 1 and escalating to the maintenance dose of 30 mg twice daily (60 mg total daily) beginning on Day 6, with dose reduction to 30 mg once daily only for patients with severe renal impairment (creatinine clearance <30 mL/min). 1
Standard Dosing Schedule
Initial Titration (Days 1-5)
The FDA-approved titration schedule is designed to minimize gastrointestinal adverse effects and must be followed precisely 1:
- Day 1: 10 mg in the morning only
- Day 2: 10 mg morning, 10 mg evening
- Day 3: 10 mg morning, 20 mg evening
- Day 4: 20 mg morning, 20 mg evening
- Day 5: 20 mg morning, 30 mg evening
- Day 6 and thereafter: 30 mg twice daily (morning and evening) 1
Maintenance Dosing
- Standard maintenance dose: 30 mg twice daily (total 60 mg/day) starting on Day 6 and continuing indefinitely 1
- Apremilast may be taken without regard to meals 1
- Tablets must be swallowed whole; do not crush, split, or chew 1
Dose Adjustments for Renal Impairment
Severe renal impairment is the only indication for dose reduction 1, 2:
- Creatinine clearance <30 mL/min: Reduce maintenance dose to 30 mg once daily 1, 2
- For initial titration in severe renal impairment, use only the morning (AM) doses from the standard titration schedule and skip all evening (PM) doses 1
- No dose adjustment is required for mild-to-moderate renal impairment 2
Hepatic Impairment
No dose adjustment is required for any degree of hepatic impairment, including severe hepatic dysfunction 2:
- Apremilast does not cause hepatotoxicity despite hepatic metabolism via cytochrome P450 enzymes 2
- Standard titration and maintenance dosing apply regardless of liver function 2
Critical Monitoring Parameters
While apremilast requires no routine laboratory monitoring 2, specific clinical parameters must be assessed:
Weight Monitoring
- Monitor body weight at every visit 2
- Discontinue apremilast if weight loss exceeds 5% from baseline 2
- Weight loss of 5-10% occurs in approximately 12% of patients versus 5% on placebo 2
Depression Screening
- Discuss depression risk before initiating therapy 2, 1
- Monitor for emergence or worsening of depression at each visit 2, 1
- Depression occurs in approximately 1% of patients 2
Gastrointestinal Effects
- Counsel patients that diarrhea and nausea occur in 70-80% within the first 2 weeks 2, 3
- Most gastrointestinal symptoms (75-80%) are mild and 60-65% resolve within the first month without intervention 2
- Elderly patients are particularly prone to dehydration and may require hospitalization 2
- Consider dose reduction or temporary suspension for severe diarrhea, nausea, or vomiting 1
Common Pitfalls to Avoid
- Do not skip the 5-day titration: The titration is mandatory to reduce gastrointestinal symptoms, not optional 1, 3
- Do not reduce the dose for hepatic impairment: Dose adjustment is indicated only for severe renal impairment 2
- Do not order routine laboratory monitoring: This adds unnecessary cost and patient burden without clinical benefit 2
- Avoid strong CYP450 inducers (rifampin, phenobarbital, carbamazepine, phenytoin) as they reduce apremilast efficacy 2
Efficacy Timeline
- Significant improvements in pruritus and skin discomfort can be seen as early as week 2 4
- At week 16, approximately 33-41% of patients achieve PASI-75 (≥75% reduction in Psoriasis Area and Severity Index) 5, 6, 7
- Efficacy is sustained through 52 weeks, with 61-80% of responders maintaining PASI-50 response 5, 6