What is the recommended dosing schedule, administration instructions, monitoring, and side effect profile for oral apremilast (Otezla) in adult patients with plaque psoriasis, psoriatic arthritis, or Behçet’s disease?

Oral Apremilast (Otezla) Dosing and Management

Apremilast is dosed at 30 mg twice daily after a 5-day titration schedule, requires no laboratory monitoring, and is indicated for moderate-to-severe plaque psoriasis, psoriatic arthritis, and Behçet's disease in adults. 1

Standard Dosing Schedule

The FDA-approved titration regimen minimizes gastrointestinal side effects and must be followed for all patients with normal renal function: 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 morning, 30 mg evening (maintenance dose) 1

Administration Instructions

• Take tablets orally without regard to meals 1
• Do not crush, split, or chew tablets 1
• Continue 30 mg twice daily indefinitely for sustained efficacy 2

Dosing in Severe Renal Impairment

For patients with creatinine clearance <30 mL/min (Cockcroft-Gault equation), reduce to 30 mg once daily: 1

• Use only the AM schedule from the titration table
• Skip all PM doses during titration
• Maintenance dose: 30 mg once daily in the morning 1

Monitoring Requirements

Apremilast requires no laboratory monitoring—a major advantage over traditional systemic agents like methotrexate and cyclosporine. 2, 3

• Before initiating therapy: Screen for history of depression, suicidal ideation, or psychiatric disorders 1
• During treatment: Monitor for new or worsening depression, especially in patients with prior psychiatric history 1
• No routine blood work required: No CBC, liver function tests, or renal panels needed for monitoring 2, 3

Side Effect Profile and Management

Common Gastrointestinal Effects (Most Frequent)

• Diarrhea, nausea, and vomiting occur most commonly within the first few weeks of treatment 1, 2
• Most gastrointestinal symptoms are mild-to-moderate and self-limited 2, 4
• The 5-day titration schedule reduces but does not eliminate GI symptoms 1

Severe Gastrointestinal Reactions (Postmarketing Reports)

Severe diarrhea, nausea, and vomiting requiring hospitalization have been reported, particularly in: 1

• Patients ≥65 years of age
• Patients taking medications causing volume depletion or hypotension
• Patients susceptible to dehydration complications 1

Management approach: 1

• Monitor high-risk patients closely during the first month
• Consider dose reduction or temporary suspension if severe GI symptoms develop
• Symptoms typically improve quickly after dose reduction or discontinuation 1

Depression and Psychiatric Effects

Apremilast increases the risk of depression and suicidal ideation: 1

• Before prescribing: Carefully weigh risks versus benefits in patients with history of depression or suicidal thoughts 1
• During treatment: Monitor for new or worsening depression, suicidal thoughts, or behavioral changes 1
• Action required: Discontinue apremilast if new or worsening psychiatric symptoms develop 1

Other Common Adverse Effects

• Headache (reported in clinical trials) 2
• Upper respiratory tract infections 2
• Weight loss (typically modest) 2
• Generally well tolerated with acceptable safety profile 2, 4, 3

Clinical Efficacy Expectations

Psoriasis Response

• Week 2: Significant improvement in pruritus and skin discomfort/pain scores 2
• Week 16: Approximately 30-33% achieve PASI 75 (75% improvement) in moderate-to-severe plaque psoriasis 2, 4
• Efficacy demonstrated in difficult-to-treat areas: nail, scalp, and palmoplantar psoriasis 2
• Sustained efficacy maintained long-term 2

Psoriatic Arthritis Response

• Week 2: Significant improvement in ACR20 response (≥20% improvement in arthritis symptoms) 2
• Efficacy sustained up to 208 weeks (4 years) 2
• Improves enthesitis, dactylitis, physical function, and fatigue 2
• Effective in both DMARD-naïve and DMARD-experienced patients 2

Contraindications

Apremilast is contraindicated in patients with known hypersensitivity to apremilast or any excipients in the formulation. 1

Critical Clinical Pitfalls to Avoid

• Never skip the 5-day titration schedule—it is designed to minimize GI side effects 1
• Do not prescribe to patients with active severe depression or suicidal ideation without psychiatric consultation 1
• Do not ignore severe diarrhea in elderly patients—hospitalization may be required for volume depletion 1
• Do not crush or split tablets—this alters drug release and may worsen side effects 1
• Do not forget to reduce dose to 30 mg once daily in severe renal impairment (CrCl <30 mL/min) 1

Combination Therapy Considerations

Apremilast can be combined with other therapies when clinically indicated, though high-quality data are limited: 5

• May be combined with biologics (etanercept, infliximab, ustekinumab) to augment efficacy (Grade C recommendation) 5
• Can be used with topical corticosteroids and vitamin D analogues 5
• Long-term safety and efficacy of combination therapy with biologics remains unknown 5

Position in Treatment Algorithm

Apremilast is positioned as an oral alternative for patients who: 5, 2, 3

• Prefer oral therapy over injectable biologics
• Have contraindications to biologics (recurrent infections, congestive heart failure, demyelinating disease) 5
• Require a medication without laboratory monitoring requirements 2, 3
• Have failed or are intolerant to topical therapy and phototherapy 1

Apremilast is less effective than TNF inhibitors (adalimumab, infliximab) and IL-17/IL-23 inhibitors for moderate-to-severe psoriasis, making it a second-line systemic option after biologics in most cases. 5, 2