What is the recommended apremilast dosing schedule for an adult with moderate-to-severe plaque psoriasis, including titration, maintenance dose, and dose adjustments for moderate renal impairment, hepatic impairment, and contraindications in pregnancy?

Apremilast Dosing in Psoriasis

Standard Dosing Schedule

Apremilast requires a mandatory 5-day titration starting at 10 mg daily and increasing by 10 mg increments to reach the maintenance dose of 30 mg twice daily, which minimizes gastrointestinal adverse effects. 1

Titration Schedule (Days 1-5)

• Day 1: 10 mg once daily (morning) 1
• Day 2: 10 mg twice daily (morning and evening) 1
• Day 3: 10 mg morning, 20 mg evening 1
• Day 4: 20 mg twice daily 1
• Day 5: 20 mg morning, 30 mg evening 1
• Day 6 onward: 30 mg twice daily (maintenance dose) 1, 2, 3

Alternative Slower Titration

• A slower titration over 13-26 days (extending the starter pack duration) significantly reduces adverse events from 50% to 25% while maintaining equivalent efficacy, though this is not the FDA-approved schedule 4
• The standard 5-day titration remains the recommended approach, but clinicians may consider slower titration for patients at high risk of gastrointestinal intolerance 4

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Dose Adjustments for Renal Impairment

For severe renal impairment (creatinine clearance <30 mL/min), reduce the maintenance dose to 30 mg once daily and administer only morning doses during titration, omitting all evening doses. 1

• Mild-to-moderate renal impairment requires no dose adjustment 1
• Baseline renal function assessment is prudent when severe impairment is suspected, though not explicitly required 5

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Hepatic Impairment

No dose adjustment is required for any degree of hepatic impairment, including severe hepatic dysfunction. 1

• Apremilast does not cause hepatotoxicity despite hepatic metabolism via cytochrome P450 enzymes 5, 1
• This distinguishes apremilast from methotrexate and makes it particularly advantageous for patients with pre-existing liver disease 5

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Pregnancy Contraindications

Apremilast is contraindicated in pregnancy based on standard pharmaceutical safety principles, though the provided guidelines do not explicitly detail pregnancy-specific contraindications 6

• Women of childbearing potential should use effective contraception during treatment
• The risk-benefit discussion should occur before initiating therapy in this population

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Pre-Treatment Counseling Requirements

Gastrointestinal Effects

• 70-80% of patients develop diarrhea or nausea within the first 2 weeks; 75-80% of these events are mild and 60-65% resolve spontaneously by week 4 without intervention. 1
• Most patients should continue therapy without dose alteration because symptoms typically improve 1
• Elderly patients (≥65 years) require closer monitoring for dehydration, as they have higher hospitalization risk from GI effects 5, 1

Depression Monitoring

• Depression occurs in approximately 1% of patients 5, 1
• Discuss depression risk before starting therapy and perform screening at every follow-up visit 5, 1

Weight Monitoring

• Approximately 12% of patients experience 5-10% body weight reduction 5, 1
• Measure body weight at each visit and discontinue apremilast if weight loss exceeds 5% from baseline 5, 1

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Laboratory Monitoring

No routine laboratory monitoring is required before or during apremilast therapy, unlike methotrexate which requires CBC, metabolic panel, and hepatitis serologies. 5, 1

• Baseline labs may be obtained on an individual basis only when severe renal impairment is suspected or complex comorbidities warrant documentation 1
• Apremilast does not cause bone marrow suppression or blood count abnormalities 5
• Clinical follow-up should focus on body weight, depression screening, and hydration status rather than laboratory parameters 5, 1

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Drug Interactions

Avoid concomitant use of strong CYP450 inducers (rifampin, phenobarbital, carbamazepine, phenytoin) because they reduce apremilast efficacy by increasing metabolism. 1

• The concern is loss of therapeutic effect, not hepatotoxicity 5

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Combination Therapy Options

Apremilast can be safely combined with methotrexate, acitretin, cyclosporine, or TNF-α inhibitors (etanercept, adalimumab, infliximab) when monotherapy provides inadequate disease control. 6, 1

• Combination with etanercept has Level II evidence 6
• Combination with infliximab may augment efficacy when clinically indicated 6

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Efficacy Benchmarks

• At week 16, approximately 29-41% of patients achieve PASI-75 with apremilast 30 mg twice daily versus 5-6% with placebo 2, 3, 7
• At week 52,61-80% of patients who continue apremilast maintain PASI-75 response 2, 7
• Apremilast 20 mg twice daily shows lower efficacy (29% PASI-75) compared to 30 mg twice daily (41% PASI-75) 3

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Common Pitfalls to Avoid

• Do not discontinue apremilast prematurely for mild-to-moderate GI symptoms in the first 2-4 weeks, as most resolve without intervention 1
• Do not reduce the dose for hepatic impairment; dose reduction is indicated only for severe renal impairment 1
• Do not order routine laboratory tests "just to be safe," as this adds unnecessary cost and patient burden without clinical benefit 5, 1
• Do not skip the titration schedule, as it is essential for minimizing adverse effects 1, 4

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Ideal Patient Populations

• Patients unable to undergo regular laboratory monitoring due to access barriers or needle phobia 5
• Patients with pre-existing liver disease 5
• Patients with complex medical comorbidities precluding other systemic therapies 1