Starting Dose of Otezla (Apremilast) for Plaque Psoriasis
Otezla (apremilast) should be initiated at a lower dose of 10 mg on day 1 and titrated up over 5 days to the maintenance dose of 30 mg twice daily to reduce the risk of gastrointestinal adverse effects. 1
Recommended Titration Schedule
The FDA-approved titration schedule for Otezla is as follows:
- Day 1: 10 mg in the morning (AM)
- Day 2: 10 mg in the morning (AM) and 10 mg in the evening (PM)
- Day 3: 10 mg in the morning (AM) and 20 mg in the evening (PM)
- Day 4: 20 mg in the morning (AM) and 20 mg in the evening (PM)
- Day 5: 20 mg in the morning (AM) and 30 mg in the evening (PM)
- Day 6 and thereafter: 30 mg twice daily (maintenance dose) 1, 2
Special Dosing Considerations
Renal Impairment
- For patients with severe renal impairment (creatinine clearance <30 mL/min), the dose should be reduced to 30 mg once daily 1, 2
- For initial titration in patients with severe renal impairment, it is recommended to follow only the AM schedule listed above and skip the PM doses 2
Administration Guidelines
- Otezla can be administered without regard to meals 2
- The tablets should not be crushed, split, or chewed 2
Common Adverse Effects
The most common adverse effects associated with apremilast include:
- Diarrhea (70-80% occur within first 2 weeks)
- Nausea
- Upper respiratory tract infections
- Headache 1
Most gastrointestinal adverse effects:
- Occur within the first 2 weeks of treatment
- Are mild to moderate in severity
- Resolve within the first month of treatment 1
Important Monitoring Considerations
- Weight loss: Monitor for weight loss >5% from baseline, which may require discontinuation of apremilast 1
- Depression: Apremilast may be associated with emergence or worsening of depression; discuss this risk with patients before initiating therapy 1
- Elderly patients: Those 65 years and older are more prone to dehydration complications from GI side effects 1
Drug Interactions
- Apremilast is metabolized by cytochrome P450
- Use with strong CYP450 inducers (e.g., rifampin, phenobarbital, carbamazepine, phenytoin) is not recommended as it may decrease apremilast efficacy 1
Efficacy
Apremilast has demonstrated efficacy in moderate to severe plaque psoriasis:
- In the ESTEEM 1 trial, 33.1% of patients achieved PASI-75 (75% reduction in Psoriasis Area and Severity Index) at week 16 compared to 5.3% with placebo 3
- Improvements are typically seen within the first few weeks of treatment, with continued improvement through week 16 3
The gradual titration schedule is specifically designed to minimize gastrointestinal adverse effects that commonly occur when initiating apremilast therapy, making it an important part of the treatment protocol to improve patient tolerability and adherence.