Apremilast

• Psoriatic Arthritis (PsA): Treatment of active psoriatic arthritis in adults, including those with concomitant plaque psoriasis.
• Plaque Psoriasis: Management of moderate to severe plaque psoriasis in adults who are candidates for phototherapy or systemic therapy.
• Behçet’s Disease: Treatment of oral ulcers associated with Behçet’s disease (approved in select regions).
• Off-Label Uses: Investigational use in other inflammatory diseases such as atopic dermatitis and hidradenitis suppurativa.

• Initiation and Maintenance:
  Dose titration over 6 days starting at 10 mg once daily, increasing to 30 mg twice daily by day 6.
• Maintenance Dose: 30 mg orally twice daily.
• Renal Impairment: Reduce to 30 mg once daily for severe renal impairment (creatinine clearance <30 mL/min).
• Administration Route: Oral tablets, with or without food.
• Pediatrics: Safety and efficacy not established.
• Elderly: No dose adjustment solely based on age.

Apremilast selectively inhibits phosphodiesterase 4 (PDE4), elevating intracellular cyclic AMP levels. This leads to decreased production of pro-inflammatory cytokines (e.g., TNF-α, IL-17, IL-23) and increased production of anti-inflammatory cytokines (e.g., IL-10). The net effect is modulation of immune and inflammatory pathways relevant to psoriasis and psoriatic arthritis.

• Absorption: Approximately 73% oral bioavailability; peak plasma concentration in ~2.5 hours.
• Distribution: Volume of distribution ~87 liters; ~68% plasma protein bound.
• Metabolism: Primarily metabolized by CYP3A4, minor CYP1A2 and CYP2A6 involvement.
• Elimination: Half-life 6–9 hours; excreted mostly as metabolites in urine (58%) and feces (39%).
• Steady State: Achieved in approximately 4 days.

• Pregnancy: No assigned FDA pregnancy category; animal studies show risk at high doses. Use only if benefits justify potential risks.
• Lactation: Unknown excretion in breast milk; breastfeeding not recommended during treatment.
• Data: Limited human data available; caution advised.

• Immunomodulator
• Phosphodiesterase 4 (PDE4) inhibitor

• Hypersensitivity to apremilast or any component of the formulation.
• Concomitant use with strong CYP3A4 inducers is generally avoided due to reduced efficacy.

• Monitor for weight loss; discontinue if unexplained or clinically significant.
• Assess for new or worsening depression or suicidal ideation.
• Watch for gastrointestinal symptoms such as diarrhea, nausea, and vomiting.
• Use caution in patients with chronic infections.
• Dose adjustment required in severe renal impairment.

• Common: Diarrhea, nausea, headache, upper respiratory tract infections, vomiting, weight loss.
• Serious: Depression, suicidal ideation, severe dehydration from diarrhea.
• Rare: Hypersensitivity reactions including angioedema.
• Timing: Gastrointestinal symptoms usually occur early; psychiatric symptoms can occur anytime.

• Strong CYP3A4 inducers (e.g., rifampin) reduce apremilast plasma levels, decreasing efficacy.
• CYP3A4 inhibitors have minimal effect; no dose adjustment typically needed.
• No significant food or alcohol interactions reported.

• FDA updates highlight warnings for weight loss and psychiatric adverse effects.
• Included in American Academy of Dermatology guidelines for psoriatic disease management.
• EMA confirms current indications with monitoring recommendations.

• Store at 20°C to 25°C (68°F to 77°F).
• Protect from moisture and light.
• Keep tablets in original container tightly closed.
• Do not freeze.
• Keep out of reach of children.