Apremilast

• Psoriatic Arthritis
• Plaque Psoriasis
• Behçet's Disease
• Oral Ulcers

Apremilast is an oral phosphodiesterase 4 (PDE4) inhibitor used in the treatment of psoriatic arthritis, plaque psoriasis, and oral ulcers associated with Behçet's disease. This small molecule medication offers a targeted approach to reducing inflammation without the immunosuppression associated with traditional systemic therapies.

Mechanism of Action

Apremilast selectively inhibits phosphodiesterase 4 (PDE4), an enzyme predominantly found in immune cells. PDE4 is responsible for degrading cyclic adenosine monophosphate (cAMP), an intracellular second messenger. By inhibiting PDE4, apremilast increases intracellular cAMP levels, which modulates the production of pro-inflammatory and anti-inflammatory mediators. This leads to decreased production of TNF-alpha, IL-23, IL-17, and other pro-inflammatory cytokines, while increasing anti-inflammatory mediators like IL-10. The net effect is reduced inflammation in the skin, joints, and other affected tissues.

Available Formulations

Apremilast is available as oral tablets in 10 mg, 20 mg, and 30 mg strengths. A starter pack is available containing tablets for the initial titration period. The tablets should be swallowed whole and can be taken with or without food.

Medical Uses

Apremilast is FDA-approved for active psoriatic arthritis in adults, moderate to severe plaque psoriasis in adults who are candidates for phototherapy or systemic therapy, and oral ulcers associated with Behçet's disease. Clinical trials demonstrated significant improvements in joint symptoms, skin clearance, and ulcer healing compared to placebo. The medication is often used in patients who prefer oral therapy or who have contraindications to biologic medications.

Dosing Guidelines

Treatment begins with a 5-day titration schedule to reduce gastrointestinal side effects: Day 1: 10 mg AM; Day 2: 10 mg AM and 10 mg PM; Day 3: 10 mg AM and 20 mg PM; Day 4: 20 mg AM and 20 mg PM; Day 5: 20 mg AM and 30 mg PM; Day 6 and thereafter: 30 mg twice daily. The maintenance dose is 30 mg twice daily. For patients with severe renal impairment (CrCl less than 30 mL/min), only the morning dose should be given (30 mg once daily) after titration.

Important Safety Information

Depression and suicidal ideation have been reported with apremilast. Patients should be carefully evaluated for risks and benefits before starting therapy, especially those with a history of depression or suicidal behavior. Weight loss has been observed; regular weight monitoring is recommended. The medication should be used with caution in patients who are underweight and discontinued if unexplained significant weight loss occurs. Apremilast should not be used with strong CYP3A4 inducers.

Drug Interactions

Strong CYP3A4 inducers (rifampin, phenobarbital, carbamazepine, phenytoin) significantly reduce apremilast exposure and should be avoided. Apremilast is not a CYP enzyme inducer or inhibitor and is unlikely to affect the metabolism of other drugs. No clinically significant interactions have been observed with methotrexate, oral contraceptives, or common medications used in psoriatic disease.

Special Populations

There are no adequate studies of apremilast in pregnant women. Animal studies showed embryofetal loss; pregnancy should be avoided during treatment. It is unknown whether apremilast is excreted in human breast milk. Safety and efficacy have not been established in pediatric patients. No dose adjustment is needed for elderly patients. Patients with severe renal impairment require dose reduction (30 mg once daily). No dose adjustment is needed for hepatic impairment.