What is the recommended dosing and monitoring for Otezla (apremilast) in an adult patient with moderate to severe plaque psoriasis or psoriatic arthritis, considering potential gastrointestinal side effects and history of kidney disease?

Otezla (Apremilast) Dosing and Monitoring for Moderate to Severe Plaque Psoriasis and Psoriatic Arthritis

Start apremilast with a 5-day titration schedule (10 mg daily on Day 1, increasing to 30 mg twice daily by Day 6) to minimize gastrointestinal side effects, and reduce the maintenance dose to 30 mg once daily in patients with severe renal impairment (creatinine clearance <30 mL/min). 1

Initial Dosing Protocol

The FDA-approved titration schedule must be followed to reduce GI adverse effects: 1

• Day 1: 10 mg in the morning only
• Day 2: 10 mg morning and evening (20 mg total daily)
• Day 3: 10 mg morning, 20 mg evening (30 mg total daily)
• Day 4: 20 mg morning and evening (40 mg total daily)
• Day 5: 20 mg morning, 30 mg evening (50 mg total daily)
• Day 6 and thereafter: 30 mg twice daily (60 mg total daily) 2, 1

Tablets should be swallowed whole without crushing, splitting, or chewing, and can be taken without regard to meals. 1

Dose Adjustment for Renal Impairment

For patients with severe renal impairment (creatinine clearance <30 mL/min), reduce the maintenance dose to 30 mg once daily. 2, 1

During the initial titration period in these patients, use only the morning doses from the standard schedule and skip all evening doses. 1 After completing the 5-day titration using only morning doses, continue with 30 mg once daily in the morning. 2

Monitoring for Gastrointestinal Side Effects

Diarrhea and nausea are the most common adverse effects, occurring in 17% of patients each, with 70-80% of GI events occurring within the first 2 weeks. 2, 1

• Most GI adverse effects are mild in severity (75-80%) and resolve within the first month (60-65%). 2
• Patients 65 years or older are at higher risk for dehydration and complications from severe diarrhea, nausea, or vomiting, and may require hospitalization. 1
• Monitor elderly patients and those taking medications that can lead to volume depletion or hypotension more closely. 1
• Consider dose reduction or temporary suspension if patients develop severe diarrhea, nausea, or vomiting. 1

The 5-day titration schedule is specifically designed to minimize these GI symptoms and should never be bypassed. 2, 1

Weight Monitoring

Monitor body weight regularly, as 12% of apremilast-treated patients experience 5-10% weight loss compared to 5% on placebo. 2

• If weight loss exceeds 5% from baseline, strongly consider discontinuing apremilast. 2
• Weight loss typically occurs early in treatment and should be assessed at each follow-up visit. 2

Depression Screening and Monitoring

Screen for history of depression and suicidal ideation before initiating apremilast, as depression was reported in approximately 1% of patients. 2, 1

• Carefully weigh risks and benefits in patients with pre-existing depression or suicidal thoughts. 1
• Counsel patients about the potential for emergence or worsening of depression before starting therapy. 2
• Monitor for new-onset or worsening depressive symptoms during treatment. 2

Laboratory Monitoring

Routine laboratory screening and monitoring are not required for apremilast, which is a major advantage over other systemic therapies like methotrexate. 2, 3

However, laboratory monitoring can be considered on an individual basis depending on patient comorbidities. 2 This lack of required monitoring makes apremilast particularly suitable for patients who cannot adhere to regular laboratory surveillance or have contraindications to agents requiring such monitoring. 2

Drug Interactions

Avoid concurrent use with strong cytochrome P450 inducers (rifampin, phenobarbital, carbamazepine, phenytoin), as these may decrease apremilast efficacy. 2

Review medication lists before initiating therapy and periodically thereafter to identify potential interactions. 2 Apremilast is metabolized hepatically via cytochrome P450, making it susceptible to interactions typical of this metabolic pathway. 2

Combination Therapy Considerations

There is currently no strong evidence supporting combined use of apremilast with other systemic therapies or phototherapy for psoriasis. 2

• Multiple case reports and small case series suggest potential benefit when combining apremilast with biologic agents like adalimumab, though this remains off-label. 2
• One small retrospective study (n=22) found that apremilast could be safely combined with biologic agents in patients with inadequate response to biologics alone, with no discontinuations due to side effects. 4
• Combination with etanercept has been reported in guidelines as potentially augmenting efficacy, though evidence is limited (Level C). 2

Common Pitfalls to Avoid

• Never skip the 5-day titration schedule, even in patients eager to reach therapeutic dosing, as this significantly increases GI adverse effects. 2, 1
• Do not forget to adjust dosing in severe renal impairment, as standard twice-daily dosing may lead to drug accumulation. 2, 1
• Do not overlook elderly patients' increased vulnerability to dehydration from GI side effects, which may require hospitalization. 1
• Remember that apremilast has slower onset and lower clearance rates compared to biologics—set appropriate patient expectations that significant improvement may take 16 weeks. 2