ApremilastRx

Trade Names: Otezla

Drug Class: Phosphodiesterase type 4 (PDE4) inhibitor

Preparations: 10-, 20-, 30-mg tablets

Dose: Starter pack titrates dose over 5 days to avoid GI side effects, day 1: 10 mg, day 2: 10 mg bid, day 3: 10 mg am, 20 mg pm, day 4: 20 mg bid, day 5: 20 mg am, 30 mg pm, day 6 and thereafter 30 mg bid.  Target dose is 30 mg bid; 20 mg bid in patients with side effects; and 30 mg qd with renal insufficiency.

Indications: Psoriatic arthritis, Psoriasis

Mechanism of Action: Inhibits PDE4 and thus increases cyclic AMP concentrations.

Contraindications: Hypersensitivity

Precautions: Caution in depression. Decrease dose 50% in severe renal impairment.

Monitoring: Monitor weight.

Pregnancy Risk: C

Adverse Effects
Common: Diarrhea (up to 17%), nausea, headache, weight loss (10%)
Less common: Vomiting, abdominal pain, depression, rash

Drug Interactions: Concurrent use of rifampin and other strong cytochrome P450 (CYP) enzyme inducers such as phenytoin decrease apremilast concentrations.

Patient Instructions: Be alert to emergence or worsening of depression. Weight loss (5-10% of body weight) may occur.

Comments: Modestly effective in psoriatic arthritis with approximate ACR20 response rates of 40% vs 20% with placebo. Skin may improve. Compared to biologics, oral dosing convenient and lower infection  risk.

Clinical Pharmacology: Well absorbed, half-life is 6-9 h. Metabolized by several CYP enzymes including CYP3A4.

Cost: $$$$$

BIBLIOGRAPHY

Kavanaugh A, Mease PJ, Gomez-Reino JJ, et al. Treatment of psoriatic arthritis in a phase 3 randomised, placebo-controlled trial with apremilast, an oral phosphodiesterase 4 inhibitor. Ann Rheum Dis 2014;73:1020-6. PMID: 24595547

Papp K, Cather JC, Rosoph L, Sofen H, et al. Efficacy of apremilast in the treatment of moderate to severe psoriasis: a randomised controlled trial. Lancet 2012;380:738-46. PMID: 22748702.