What is the recommended dosing schedule, contraindications, dose adjustments, common adverse effects, and monitoring requirements for Otezla (apremilast) in adults with moderate‑to‑severe plaque psoriasis or active psoriatic arthritis?

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

Recommended Dosing Schedule

Apremilast requires a 5-day titration schedule to minimize gastrointestinal adverse effects, followed by maintenance dosing of 30 mg twice daily indefinitely. 1

Standard Titration Protocol

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

Administration Guidelines

• Apremilast can be taken without regard to meals 1
• Do not crush, split, or chew the tablets 1
• Continue treatment for a minimum of 8 weeks to assess response, with optimal duration of approximately 24 weeks for better efficacy 2

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Dose Adjustments

Severe Renal Impairment

In patients with creatinine clearance <30 mL/min, reduce the dose to 30 mg once daily. 1

• Use only the morning (AM) schedule from the titration table and skip all evening (PM) doses 1
• This applies to both the titration phase and maintenance therapy 1

No Other Dose Adjustments Required

• No hepatic dose adjustment is specified in the FDA label 1
• No age-based dose adjustments are required 1

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Contraindications

The only absolute contraindication to apremilast is known hypersensitivity to apremilast or any excipients in the formulation. 1

Relative Contraindications and Cautions

• Apremilast has a favorable safety profile and can be used in patients with complex medical conditions where other systemic agents are contraindicated, including those with hepatitis B or C, HIV, or patients on polypharmacy 3, 2
• No contraindication exists for renal or hepatic impairment, though dose reduction is required for severe renal impairment 3, 1

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Common Adverse Effects

Most Frequent Adverse Events

Diarrhea (17%) and nausea (17%) are the most common adverse effects, typically occurring within the first 2 weeks and resolving within the first month. 3, 1

The most commonly reported adverse reactions (≥5% and more frequent than placebo) include: 1

• Diarrhea: 17% (vs. 6% placebo)
• Nausea: 17% (vs. 7% placebo)
• Upper respiratory tract infection: 9% (vs. 6% placebo)
• Tension headache: 8% (vs. 4% placebo)
• Headache: 6% (vs. 4% placebo)

Serious Adverse Effects Requiring Monitoring

Severe diarrhea, nausea, and vomiting: Postmarketing reports indicate some patients require hospitalization, particularly those ≥65 years or taking medications causing volume depletion 1

Depression and suicidal ideation: During controlled trials, 1.3% of apremilast-treated patients reported depression vs. 0.4% on placebo, with one suicide attempt in the apremilast group 1

Weight loss: 12% of patients experienced 5-10% body weight decrease, and 2% experienced ≥10% decrease 1

Discontinuation Rates

• 6.1% of apremilast-treated patients discontinued due to adverse reactions vs. 4.1% on placebo 1
• Most common reasons for discontinuation: nausea (1.6%), diarrhea (1.0%), and headache (0.8%) 1

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Monitoring Requirements

Apremilast requires minimal laboratory monitoring compared to other systemic therapies, which is a major advantage. 3, 4, 2

Pre-Treatment Assessment

• No mandatory laboratory screening is required before initiating apremilast 3, 2
• Review medication list for strong CYP450 inducers (rifampin, phenobarbital, carbamazepine, phenytoin), which are not recommended for concurrent use 3, 1
• Screen for history of depression or suicidal ideation 1

During Treatment Monitoring

• Weight monitoring: Check weight regularly; if unexplained or clinically significant weight loss occurs (>5% from baseline), evaluate and consider discontinuation 1
• Depression screening: Advise patients, caregivers, and families to monitor for emergence or worsening of depression, suicidal thoughts, or mood changes 1
• Gastrointestinal symptoms: Monitor patients ≥65 years or those at risk for dehydration more closely for severe diarrhea, nausea, or vomiting 1
• Routine laboratory monitoring: Can be considered on an individual basis but is not required 3

Response Assessment Timeline

• Assess clinical response at 8 weeks minimum, with definitive assessment at 16-24 weeks 2, 5
• If no response after 16 weeks, consider discontinuation or alternative therapy 3

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Critical Drug Interactions

Do not use apremilast with strong CYP450 enzyme inducers, as they significantly reduce apremilast exposure and may result in loss of efficacy. 3, 1

Contraindicated Combinations

• Rifampin 3, 1
• Phenobarbital 3, 1
• Carbamazepine 3, 1
• Phenytoin 3, 1

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Special Populations and Clinical Scenarios

Pregnancy and Lactation

• Pregnancy Category: No established drug-associated risk, but animal studies show potential for fetal loss at exposures 2.1-times the maximum recommended human dose 1
• A pregnancy exposure registry exists (1-877-311-8972) 1
• Use only if benefit justifies potential risk to fetus 3

Efficacy in Difficult-to-Treat Areas

• Apremilast demonstrates effectiveness in scalp, palmoplantar, and nail psoriasis 6, 4, 2
• Rapid improvement in pruritus can be seen as early as week 2 4

Combination Therapy

• Apremilast may be combined with topical corticosteroids or vitamin D analogues to augment efficacy 3
• Can be combined with biologics (ustekinumab, etanercept, infliximab) when clinically indicated, though evidence is limited (Strength of Recommendation C) 3
• No strong evidence supports routine combination with other systemic or phototherapy treatments 3

Real-World Efficacy

• PASI-75 response rates: 47.5% at week 24 and 25% at week 52 in real-world settings 5
• PASI-90 response rates: 30% at week 24 and 35% at week 52 5
• Approximately 60% of patients achieve and maintain DLQI 0-1 from week 24 through week 52 5
• Higher response rates may be observed in patients with lower baseline PASI scores 7

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Key Clinical Pitfalls to Avoid

Do not skip the 5-day titration schedule, as this significantly increases gastrointestinal adverse effects and may lead to early discontinuation 1

Do not discontinue prematurely for gastrointestinal symptoms that occur in the first 2 weeks, as 70-80% of these events are mild and 60-65% resolve within the first month 3

Consider dose reduction or temporary suspension if severe diarrhea, nausea, or vomiting develops, rather than immediate discontinuation 1

Counsel patients about potential depression before initiating therapy, particularly those with pre-existing psychiatric conditions 1

For elderly patients or those on diuretics, provide extra counseling about gastrointestinal adverse effects and the risk of dehydration requiring hospitalization 1