Apremilast is an oral, small-molecule inhibitor of phosphodiesterase 4 (PDE4) used in the management of moderate to severe plaque psoriasis and active psoriatic arthritis. It modulates intracellular inflammatory pathways by increasing cyclic AMP (cAMP) levels, leading to a downregulation of pro-inflammatory mediators and an upregulation of anti-inflammatory mediators. It is a targeted synthetic disease-modifying antirheumatic drug (tsDMARD).
Adult: For Psoriasis/Psoriatic Arthritis: Titration: Day 1: 10mg AM; Day 2: 10mg AM & PM; Day 3: 10mg AM & 20mg PM; Day 4: 20mg AM & PM; Day 5: 20mg AM & 30mg PM; Day 6 onwards: 30mg twice daily. Maintenance: 30mg orally twice daily.
Note: Can be taken with or without food. Swallow tablet whole with water. Do not crush, split, or chew. Strictly adhere to the 5-day titration schedule to minimize GI side effects. If treatment is interrupted for more than 3 days, restart using the initial titration schedule.
Apremilast selectively inhibits phosphodiesterase 4 (PDE4), an enzyme that degrades cyclic adenosine monophosphate (cAMP) within immune cells (e.g., neutrophils, monocytes, T-cells). Inhibition of PDE4 leads to increased intracellular cAMP levels. Elevated cAMP modulates key pro-inflammatory pathways by down-regulating the expression of pro-inflammatory cytokines (e.g., TNF-α, IL-17, IL-23, IFN-γ) and up-regulating anti-inflammatory cytokines (e.g., IL-10). This results in a net anti-inflammatory and immunomodulatory effect without causing broad immunosuppression.
Pregnancy: Category C (US FDA). Animal studies showed teratogenicity. There are no adequate and well-controlled studies in pregnant women. Use during pregnancy only if the potential benefit justifies the potential risk to the fetus. Indian guidelines recommend effective contraception during and for at least 3 days after stopping therapy.
Driving: Apremilast may cause dizziness or fatigue. Patients should be advised not to drive or operate machinery if they experience these effects.
| Rifampicin (Strong CYP450 Inducer) | Markedly decreases apremilast exposure (AUC reduced by ~72%). May lead to loss of efficacy. | Major |
| Phenobarbital, Phenytoin, Carbamazepine (Strong CYP450 Inducers) | Significantly decreases apremilast plasma concentrations. Loss of therapeutic effect expected. | Major |
| Ketoconazole, Itraconazole (Strong CYP3A4 Inhibitors) | Increases apremilast AUC by ~40%. Monitor for increased side effects. | Moderate |
| Other PDE4 Inhibitors (e.g., Roflumilast) | Potential for additive pharmacodynamic effects and increased side effects (e.g., GI, weight loss). | Moderate |