How do I start apremilast in an adult with moderate-to-severe plaque psoriasis who has normal baseline complete blood count, liver function tests, and serum creatinine, has been screened negative for latent tuberculosis and hepatitis, is not pregnant or nursing, and has no severe renal impairment?

How to Start Apremilast in Psoriasis

Begin apremilast with a mandatory 5-day dose titration starting at 10 mg on Day 1 morning, escalating to the maintenance dose of 30 mg twice daily by Day 6, taken without regard to meals. 1

Dose Titration Schedule

The FDA-approved titration is designed to minimize gastrointestinal symptoms and must be followed in all patients: 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 onward: 30 mg morning, 30 mg evening (maintenance dose) 1

Do not crush, split, or chew the tablets. 1 Apremilast can be taken with or without food. 1

Dose Modification for Renal Impairment

For patients with severe renal impairment (creatinine clearance <30 mL/min), reduce the dose to 30 mg once daily. 1, 2 During the initial titration, use only the morning doses from the schedule above and skip all evening doses. 1

No dose adjustment is required for hepatic impairment of any severity. 2

Pre-Treatment Counseling

Gastrointestinal Symptoms

Inform patients that 70-80% will experience diarrhea or nausea within the first 2 weeks, but 75-80% of these events are mild and 60-65% resolve spontaneously within the first month without intervention. 2, 3 Most patients should continue therapy without dose modification as symptoms typically resolve by week 4. 3

Elderly patients (≥65 years) require closer monitoring for dehydration from GI effects, as they are at higher risk for hospitalization. 1, 3

Depression Monitoring

Discuss the risk of depression (occurring in ~1% of patients) before starting therapy and plan to screen for emergence or worsening of depression at each visit. 2

Weight Loss

Inform patients that 12% experience 5-10% weight loss. 2 Monitor body weight at every visit and discontinue apremilast if weight loss exceeds 5% from baseline. 2

Baseline Assessment

No routine laboratory monitoring is required before starting apremilast. 2 This distinguishes apremilast from methotrexate, which requires CBC, comprehensive metabolic panel, hepatitis serologies, and liver fibrosis assessment at baseline. 4, 5

Consider obtaining baseline labs on an individual basis only if: 2

• Severe renal impairment is suspected (to guide dose adjustment)
• The patient has complex comorbidities requiring documentation

Do not order routine labs "just to be safe"—this adds unnecessary cost and patient burden without clinical benefit. 2

Ongoing Monitoring

No routine laboratory monitoring is needed during apremilast therapy. 2 Clinical monitoring at each visit should include: 2

• Body weight (discontinue if >5% loss from baseline)
• Depression screening (assess mood and suicidal ideation)
• Hydration status (especially in elderly patients)

Drug Interactions

Avoid concomitant use of strong CYP450 inducers (rifampin, phenobarbital, carbamazepine, phenytoin), as they reduce apremilast efficacy by increasing its metabolism. 2 The concern is loss of therapeutic effect, not toxicity.

Management of Inadequate Response

If response is insufficient after 16 weeks of 30 mg twice daily, consider: 6

• Combination therapy with topical corticosteroids, vitamin D analogues, or phototherapy 6
• Switching to a biologic agent if psoriasis is severe, as newer biologics demonstrate superior efficacy compared to apremilast monotherapy 7

Apremilast can be safely combined with methotrexate, acitretin, cyclosporine, or TNF inhibitors (etanercept, adalimumab) when monotherapy is inadequate. 4, 6 In one retrospective study, 81% of patients achieved PASI-75 at week 12 when apremilast was added to an existing systemic or biologic therapy. 6

Common Pitfalls to Avoid

• Do not skip the 5-day titration—it is mandatory to reduce GI symptoms 1
• Do not prematurely discontinue for mild-to-moderate GI symptoms in the first 2-4 weeks, as most resolve spontaneously 3
• Do not reduce the dose for hepatic impairment—dose adjustment is only for severe renal impairment 2, 1
• Do not order routine labs—apremilast does not cause bone marrow suppression, hepatotoxicity, or require laboratory monitoring 2

Advantages in Clinical Practice

Apremilast is particularly advantageous for patients who: 2

• Cannot undergo regular laboratory monitoring due to access barriers or needle phobia
• Have pre-existing liver disease (no hepatotoxicity risk)
• Have complex medical comorbidities precluding other systemic agents