Otezla Apremilast Tablets

1. Indications and Usage
Plaque Psoriasis:
Indicated for adult patients with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy.
Psoriatic Arthritis:
Indicated for adult patients with active psoriatic arthritis, alone or in combination with methotrexate.
Oral and Genital Ulcers:
Indicated for oral ulcers in patients with Behçet’s disease and genital ulcers in patients with Behçet’s disease.
2. Dosage and Administration
Route of Administration:
For Oral Use ONLY.
Recommended Dosage (Psoriasis/PsA):
Dose: 30 mg twice daily, approximately 12 hours apart.
Dose Titration: To minimize gastrointestinal side effects, the dose is titrated over 5 days:
Day 1: 10 mg (morning).
Day 2: 10 mg (morning and evening).
Day 3: 10 mg (morning), 20 mg (evening).
Day 4: 20 mg (morning and evening).
Day 5: 20 mg (morning), 30 mg (evening).
Day 6 and thereafter: 30 mg (morning and evening).
Administration Instructions:
Swallow tablets whole; do not crush, chew, or split.
Can be taken with or without food.
Renal Impairment:
Severe Renal Impairment (CLcr <30 mL/min) or ESRD: The recommended dose is 30 mg once daily. No titration is required for the evening dose (omit).
3. Mechanism of Action
PDE4 Inhibition:
Apremilast is an intracellular enzyme inhibitor that selectively inhibits phosphodiesterase 4 (PDE4), the major cAMP-degrading enzyme in immune cells.
Anti-inflammatory Effect:
By inhibiting PDE4, intracellular cAMP levels increase, leading to the downregulation of pro-inflammatory mediators (e.g., TNF-α, IL-17, IL-23) and upregulation of anti-inflammatory mediators (e.g., IL-10).
4. Safety and Warnings
Weight Loss:
Weight loss has been observed. Monitor weight periodically. Discontinue if significant, unexplained weight loss occurs.
Depression and Mood Changes:
Depression, suicidal ideation, and mood changes have been reported. Patients with a history of depression should be monitored closely.
Drug Interactions:
Concomitant use with strong CYP450 inducers (e.g., rifampin) may decrease efficacy.
Upper Respiratory Tract Infections:
Increased incidence of upper respiratory tract infections has been reported.
Adverse Reactions
Most Common:
Diarrhea, nausea, headache, vomiting, and upper respiratory tract infection.
Other:
Nasopharyngitis, insomnia, and dyspepsia.
Drug Interactions
CYP450 Inducers:
Strong inducers of CYP3A4 (e.g., rifampin, phenobarbital) can significantly reduce apremilast exposure and efficacy.
Substrates:
Apremilast does not significantly inhibit or induce major CYP enzymes at clinically relevant concentrations.
Pharmaceutical Information
Chemical Composition:
Active Ingredient: Apremilast.
Available Strength: 10 mg, 20 mg, 30 mg tablets.
Appearance: Pink (10 mg), Brown (20 mg), Light Brown (30 mg) diamond-shaped film-coated tablets.
Storage: Store at 20°C–25°C (68°F–77°F); excursions permitted to 15°C–30°C (59°F–86°F).