Apremilast is a novel, orally administered small-molecule inhibitor of phosphodiesterase 4 (PDE4). It modulates intracellular cyclic adenosine monophosphate (cAMP) levels, leading to a downregulation of pro-inflammatory mediators and an upregulation of anti-inflammatory mediators. It is specifically indicated for the treatment of active psoriatic arthritis (PsA) and moderate to severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy.
Adult: For PsA and Plaque Psoriasis: Recommended maintenance dose is 30 mg twice daily. MUST BE TITRATED: Day 1: 10 mg AM. Day 2: 10 mg AM and PM. Day 3: 10 mg AM and 20 mg PM. Day 4: 20 mg AM and PM. Day 5: 20 mg AM and 30 mg PM. Day 6 and onward: 30 mg twice daily. The 10mg tablet is primarily used for this titration.
Note: Can be taken with or without food. Swallow the tablet whole with water. Do not crush, split, or chew. If a dose is missed, take it as soon as remembered, then resume the normal schedule. Do not take two doses to make up for a missed dose.
Apremilast selectively inhibits the intracellular enzyme phosphodiesterase 4 (PDE4). Inhibition of PDE4 results in increased levels of cyclic adenosine monophosphate (cAMP) within immune cells (e.g., neutrophils, monocytes, T-cells). Elevated cAMP activates protein kinase A (PKA), which subsequently phosphorylates and inhibits key transcription factors like Nuclear Factor kappa B (NF-ÎșB).
Pregnancy: Category C. Animal studies have shown adverse effects (embryo-fetal lethality, 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. Pregnancy should be excluded before starting therapy. Effective contraception is recommended for women of childbearing potential.
Driving: Apremilast may cause dizziness and fatigue. Patients should be cautioned about operating machinery or driving until they are certain the medication does not affect them adversely.
| Strong CYP450 Inducers (e.g., Rifampicin, Carbamazepine, Phenytoin, Phenobarbital, St. John's Wort) | Significantly decrease apremilast exposure (AUC), potentially reducing efficacy. | Major |
| Strong CYP450 Inhibitors (e.g., Ketoconazole, Itraconazole, Clarithromycin, Ritonavir) | May increase apremilast exposure. However, no dosage adjustment is recommended as the increase is not clinically significant. | Moderate |
| Other Immunosuppressants/Therapy (e.g., Methotrexate, Biologics) | Concomitant use may increase risk of infections. Used together in clinical practice with monitoring, but not routinely recommended without specialist supervision. | Moderate |