Otezla (Apremilast) Titration Schedule
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, 2, 3
Recommended Titration Schedule
| Day | Morning Dose | Evening Dose |
|---|---|---|
| Day 1 | 10 mg | None |
| Day 2 | 10 mg | 10 mg |
| Day 3 | 10 mg | 20 mg |
| Day 4 | 20 mg | 20 mg |
| Day 5 | 20 mg | 30 mg |
| Day 6 & thereafter | 30 mg | 30 mg |
This gradual titration approach is specifically designed to minimize gastrointestinal side effects, which are among the most common adverse reactions to apremilast. Approximately 70-80% of GI adverse effects occur within the first 2 weeks of treatment, and proper titration can help reduce their severity 1.
Special Dosing Considerations
Renal Impairment
- Severe renal impairment (creatinine clearance <30 mL/min): Reduce dose to 30 mg once daily 1, 2, 3
- For initial titration in patients with severe renal impairment, use only the morning schedule from the titration table and skip the evening doses 3
Managing Common Side Effects
The most common adverse effects associated with apremilast include:
- Diarrhea (most common)
- Nausea
- Upper respiratory tract infections
- Headache
Important Monitoring Considerations:
- Most GI side effects occur within the first 2 weeks and resolve within the first month without dose adjustment 1
- Monitor for weight loss >5% from baseline, which may require discontinuation of therapy 1
- Be vigilant for signs of depression or suicidal ideation, which have been reported in approximately 1% of patients 1
- Elderly patients (≥65 years) are at higher risk for dehydration complications from GI side effects and should be monitored more closely 1, 3
Drug Interactions
Apremilast is metabolized by cytochrome P450 enzymes. Avoid concomitant use with strong CYP450 inducers such as:
- Rifampin
- Phenobarbital
- Carbamazepine
- Phenytoin
These medications may significantly decrease the efficacy of apremilast 1, 2.
Clinical Pearls
- Apremilast can be administered without regard to meals 3
- Do not crush, split, or chew the tablets 3
- The titration schedule is essential - skipping it increases the risk of significant GI side effects that could lead to discontinuation
- No routine laboratory monitoring is required for patients on apremilast, which is an advantage over many other systemic psoriasis treatments 1
- If severe diarrhea, nausea, or vomiting occurs, consider dose reduction or temporary suspension of treatment 3
Following this titration schedule carefully will optimize patient tolerance and improve medication adherence, leading to better clinical outcomes for patients with psoriasis or psoriatic arthritis.