Apremilast is an oral small molecule inhibitor of phosphodiesterase 4 (PDE4) specific for cyclic adenosine monophosphate (cAMP). PDE4 inhibition results in increased intracellular cAMP levels. The specific mechanism(s) by which apremilast exerts its therapeutic action is not well defined.
OTEZLA/OTEZLA XR, an inhibitor of phosphodiesterase 4 (PDE4), is indicated for the treatment of:
Adult patients with:
- Active psoriatic arthritis
- Plaque psoriasis who are candidates for phototherapy or systemic therapy
- Oral ulcers associated with Behçet’s Disease
Pediatric patients 6 years of age and older with:
- Active psoriatic arthritis
- Moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy
In the pediatric population, OTEZLA is indicated for patients weighing at least 20 kg, and OTEZLA XR is indicated for patients weighing at least 50 kg.
Recommended Dosage in Adult and Pediatric Patients with Psoriatic Arthritis, Plaque Psoriasis, and Behçet’s Disease
Adult Patients with Psoriatic Arthritis, Plaque Psoriasis, or Behçet’s Disease
The recommended initial dosage titration from Day 1 to Day 5 is shown in Table 1. Following the 5-day titration with OTEZLA, the recommended maintenance dosage is OTEZLA 30 mg twice daily or OTEZLA XR 75 mg once daily taken orally starting on Day 6. This titration is intended to reduce the gastrointestinal symptoms associated with initial therapy.
Table 1: Dosage Titration Schedule for Adult Patients with Psoriatic Arthritis, Plaque Psoriasis, or Behçet’s Disease
| OTEZLA Dosage Titrationa | OTEZLA/OTEZLA XR Maintenance Dosage | |||||||||
| Day 1 | Day 2 | Day 3 | Day 4 | Day 5 | Day 6 & thereafter | |||||
| AM | AM | PM | AM | PM | AM | PM | AM | PM | ||
| 10 mg | 10 mg | 10 mg | 10 mg | 20 mg | 20 mg | 20 mg | 20 mg | 30 mg | OTEZLA 30 mg BID OR OTEZLA XR 75 mg QD | |
BID = twice daily; QD = once daily
a OTEZLA tablets should be used for the initial titration regardless of whether OTEZLA or OTEZLA XR will be used for the maintenance dosage.
Pediatric Patients 6 Years of Age and Older and Weighing at Least 20 kg with Psoriatic Arthritis
Moderate to Severe Plaque Psoriasis
The recommended dosage for pediatric patients 6 years of age and older and weighing at least 20 kg with psoriatic arthritis or moderate to severe plaque psoriasis is based on body weight. Following the appropriate initial titration schedule shown in Table 2, the recommended maintenance dosage is:
- For pediatric patients who weigh at least 50 kg: OTEZLA 30 mg twice daily or OTEZLA XR 75 mg once daily taken orally
- For pediatric patients who weigh from 20 kg to less than 50 kg: OTEZLA 20 mg twice daily taken orally
This titration is intended to reduce the gastrointestinal symptoms associated with initial therapy.
Table 2: Dosage Titration Schedule for Pediatric Patients 6 Years of Age and Older and Weighing at Least 20 kg with Psoriatic Arthritis or Moderate to Severe Plaque Psoriasis
|
|
OTEZLA Dosage Titrationa | OTEZLA/OTEZLA XR Maintenance Dosage | |||||||||
| Body Weight | Day 1 | Day 2 | Day 3 | Day 4 | Day 5 | Day 6 & thereafter | |||||
| AM | AM | PM | AM | PM | AM | PM | AM | PM | |||
| 50 kg or more | 10 mg | 10 mg | 10 mg | 10 mg | 20 mg | 20 mg | 20 mg | 20 mg | 30 mg | OTEZLA 30 mg BID OR OTEZLA XR 75 mg QD | |
| 20 kg to less than 50 kg | 10 mg | 10 mg | 10 mg | 10 mg | 20 mg | 20 mg | 20 mg | 20 mg | 20 mg | OTEZLA 20 mg BID | |
BID = twice daily; QD = once daily
a OTEZLA tablets should be used for the initial titration regardless of whether OTEZLA or OTEZLA XR will be used for the maintenance dosage.
- Psoriatic Arthritis: The most common adverse reactions (≥ 5%) are diarrhea, nausea, and headache
- Plaque Psoriasis: The most common adverse reactions (≥ 5%) are diarrhea, nausea, upper respiratory tract infection, and headache, including tension headache
- Behçet’s Disease: The most common adverse reactions (≥ 10%) are diarrhea, nausea, headache, and upper respiratory tract infection
- Hypersensitivity: Cases of angioedema and anaphylaxis have been reported during post marketing surveillance. Avoid the use of OTEZLA/OTEZLA XR in patients with known hypersensitivity to apremilast or to any of the excipients in the formulation. If signs or symptoms of serious hypersensitivity reactions develop during treatment, discontinue OTEZLA/OTEZLA XR and institute appropriate therapy.
- Diarrhea, Nausea, and Vomiting: Consider OTEZLA/OTEZLA XR dosage reduction or suspension if patients develop severe diarrhea, nausea, or vomiting
- Depression: Advise patients, their caregivers, and families to be alert for the emergence or worsening of depression, suicidal thoughts or other mood changes and if such changes occur to contact their healthcare provider. Carefully weigh risks and benefits of treatment with OTEZLA/OTEZLA XR in patients with a history of depression and/or suicidal thoughts or behavior
- Weight Decrease: Monitor weight regularly. If unexplained or clinically significant weight loss occurs, evaluate weight loss and consider discontinuation of OTEZLA/OTEZLA XR
- Drug Interactions: Use with strong cytochrome P450 enzyme inducers (e.g., rifampin, phenobarbital, carbamazepine, phenytoin) is not recommended because loss of efficacy may occur