Dosing and uses of Otezla (apremilast)
Adult dosage forms and strengths
tablet
- 10mg
- 20mg
- 30mg
Psoriatic Arthritis
Indicated for active psoriatic arthritis
Day 1: 10 mg in 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 thereafter: 30 mg PO BId
Psoriasis
Indicated for moderate-to-severe plaque psoriasis in adults who are candidates for phototherapy or systemic therapy
Day 1: 10 mg in 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 thereafter: 30 mg PO BId
Dosage modifications
Severe renal impairment (CrCl <30 mL/min): Reduce dose to 30 mg PO qDay
Mild-to-moderate renal impairment: No dosage adjustment required
Hepatic impairment: No dosage adjustment required
Administration
To reduce risk of GI symptoms associated with initial therapy, titrate to recommended dose (30 mg PO BID) according to the dosage schedules listed above
Can be administered without regard to meals
Swallow tablet whole; do not crush, split, or chew
Pediatric dosage forms and strengths
Safety and efficacy not established
Otezla (apremilast) adverse (side) effects
1-10%
Diarrhea (7.7-9.3%)
Nausea (7.4-8.9%)
Headache (4.8-5.9%)
Upper respiratory tract infection (0.6-3.9%)
Vomiting (0.8-3.2%)
Nasopharyngitis (0.2-2.6%)
Upper abdominal pain (0.6-2%)
Warnings
Contraindications
Hypersensitivity
Cautions
Associated with an increase in adverse reactions of depression; before using, evaluate patient for history of depression and/or suicidal thoughts or behavior
Weight decrease of 5-10% of body weight reported in 10-12% of patients
Coadministration with strong CYP inducers (eg, rifampin, carbamazepine, phenobarbital phenytoin) may occur and result in a loss of efficacy of apremilast; therefore, coadministration is not recommended
Pregnancy and lactation
Pregnancy category: C; Pregnancy registry 1-877-311-8972
Lactation: Unknown if distributed in human breast milk; caution required
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Otezla (apremilast)
Mechanism of action
Oral small molecule inhibitor of phosphodiesterase-4 specific for cAMP, resulting in increased intracellular cAMP levels
The specific mechanism by which apremilast exerts it therapeutic action in psoriatic arthritis is not well defined
Absorption
Absolute bioavailability: 73%
Peak plasma time: 2.5 hr
Coadministration with food does not alter absorption
Distribution
Protein bound: 68%
Vd: 87 L
Metabolism
Apremilast is a major circulating component (45%) followed by inactive metabolite M12 (39%), a glucuronide conjugate of O-demethylated apremilast
Metabolized by both CYP oxidative metabolism with subsequent glucuronidation and non-CYP mediated hydrolysis
In vitro CYP metabolism primarily by CYP3A4, with minor contribution from CYP1A2 and CYP2A6
Elimination
Half-life: 6-9 hr
Clearance: 10 L/hr
Excretion: 58% urine; 39% feces
