The Food and Drug Administration (FDA) has approved a new drug, apremilast (Otezla), to treat active psoriatic arthritis. Psoriatic arthritis involves local and systemic chronic inflammation. Apremilast is a new chemical entity, a phosphodiesterase-4 inhibitor, which is specific for cyclic adenosine monophosphate (cAMP). This inhibition increases intracellular cAMP levels. As a second messenger (meaning that it signals physiologic cell changes), cAMP mediates the action of many hormones, such as epinephrine, on their target cells. Additionally, cAMP controls a network of proinflammatory and antiinflammatory mediators.
Apremilast joins corticosteroids, tumor necrosis factor blockers, and an interleukin-12/interleukin-23 inhibitor as treatment options for psoriatic arthritis. Whereas the actions of the other drugs are specific to particular inflammatory agents, apremilast works higher up in the inflammatory cascade and has effects on several mediators, including a decrease in the expression of inducible nitric oxide synthase, a decrease in tumor necrosis factor [alpha], a decrease in interleukin-23, and an increase in interleukin-10. Apremilast is thought to restore the balance of proinflammatory and antiinflammatory mediators. In phase 2 studies of subjects with psoriasis and psoriatic arthritis, apremilast reversed inflammation of the skin and joints and significantly reduced clinical symptoms.
Apremilast carries three warnings and precautions, although there are no black box warnings. First, the drug may exacerbate or produce depression, including serious depression, in a small number of patients. Second, apremilast induced weight loss (between 5% and 10% of body weight) in about 10% of patients undergoing therapy at the 30-mg, twice-daily maintenance dosage. Finally, apremilast shouldn't be coadministered with drugs that are strong inducers of isoenzymes in the cytochrome P-450 (CYP) system, such as rifampin, phenobarbitol, carbamazepine, and phenytoin. Because apremilast is metabolized extensively by the CYP isoenzyme system, especially CYP3A4, drugs that increase levels of CYP isoenzymes will cause excessive metabolism of apremilast and a decrease in its effectiveness.
The most common adverse effects of apremilast in trials were diarrhea, headache, and nausea. The drug's effects on pregnant women haven't yet been studied. A pregnancy-exposure registry has been created to monitor pregnancy outcomes in women who take apremilast during pregnancy.
Nurses should take a complete drug history before a patient begins therapy with apremilast. Drugs that are strong CYP isoenzyme inducers shouldn't be given to patients taking apremilast. Nurses caring for patients who are to start apremilast should assess them for a history of depression; patients and their families should receive education regarding the possibility of emerging or worsening depression and be instructed to notify the prescriber if either occurs. Nurses should inform patients of the possibility of weight loss and the need to have their weight monitored while they're taking apremilast. If unexplained or clinically significant weight loss occurs, the patient should be evaluated; apremilast may need to be discontinued. Patient education on the commencement of apremilast therapy should include the need to titrate the dose upward over six days until the recommended maintenance dosage of 30 mg twice daily is reached. Titration helps to decrease the risk of gastrointestinal adverse effects. Women who become pregnant while taking apremilast should be encouraged to enroll in the voluntary pregnancy-exposure registry, which they can do by calling (877) 311-8972.
Complete FDA prescribing information can be found at http://1.usa.gov/1okNQ0f.