apremilast

Apremilast is an oral small-molecule medication that inhibits phosphodiesterase 4 (PDE4). By blocking PDE4, it increases intracellular cyclic AMP in immune cells, leading to downregulation of inflammatory mediators such as TNF-α, IL-17, and IL-23, and a reduction in inflammation in skin and joints.

It is approved for adults with active plaque psoriasis and for adults with psoriatic arthritis. These conditions involve immune-driven inflammation of the skin and joints, and apremilast is used when topical therapies or other systemic options are insufficient or unsuitable.

The drug is taken by mouth as tablets with a titration schedule to reduce gastrointestinal side effects. The usual maintenance dose is 30 mg twice daily, taken consistently with or without food. Concomitant potent inhibitors or inducers of CYP3A4 can alter exposure, so dose adjustments are advised or its use avoided in certain drug combinations; in patients with severe hepatic impairment, use is not recommended.

Apremilast is rapidly absorbed, with peak plasma levels reached within a few hours. It is primarily metabolized in the liver by CYP3A4 (with minor contributions from CYP1A2) and is eliminated in urine and feces; the elimination half-life is approximately 9 to 14 hours.

Common adverse events include nausea, diarrhea, vomiting, headache, upper respiratory tract infection, and weight loss. Psychiatric adverse effects such as depression or mood changes, and, rarely, suicidality, have been reported; patients should report new or worsening mood symptoms to a clinician. Apremilast was approved by the U.S. Food and Drug Administration in 2014 for plaque psoriasis and later for psoriatic arthritis, and is marketed under the name Otezla.