Version October 2024
Behçet disease, psoriasis, or psoriatic arthritis: Oral: Initial: 10 mg in the morning on day 1. Titrate upward by additional 10 mg per day on days 2 to 5 as follows: Day 2: 10 mg twice daily; Day 3: 10 mg in the morning and 20 mg in the evening; Day 4: 20 mg twice daily; Day 5: 20 mg in the morning and 30 mg in the evening. Maintenance dose: 30 mg twice daily starting on day 6.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Note: Renal function may be estimated using the Cockcroft-Gault formula for dosage adjustment purposes.
CrCl ≥30 mL/minute: No dosage adjustment necessary.
CrCl <30 mL/minute: Initial: 10 mg once daily in the morning on days 1 to 3; titrate using morning doses only (skip evening doses) to 20 mg once daily on days 4 and 5. Maintenance dose: 30 mg once daily in the morning starting on day 6.
No dosage adjustment necessary.
Weight loss, unexplained or clinically significant: Evaluate and consider discontinuing apremilast.
Refer to adult dosing.
(For additional information see "Apremilast: Pediatric drug information")
Psoriasis, plaque (moderate to severe): Note: Initial dose titration is intended to reduce GI symptoms.
Children ≥6 years and Adolescents, weighing 20 to <50 kg:
Day 1: Oral: 10 mg once daily in the morning.
Day 2: Oral: 10 mg twice daily.
Day 3: Oral: 10 mg in the morning and 20 mg in the evening.
Day 4 and thereafter: Oral: 20 mg twice daily.
Children ≥6 years and Adolescents, weighing ≥50 kg:
Day 1: Oral: 10 mg once daily in the morning.
Day 2: Oral: 10 mg twice daily.
Day 3: Oral: 10 mg in the morning and 20 mg in the evening.
Day 4: Oral: 20 mg twice daily.
Day 5: Oral: 20 mg in the morning and 30 mg in the evening.
Day 6 and thereafter: Oral: 30 mg twice daily.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Psoriasis, plaque (moderate to severe):
Children ≥6 years and Adolescents, weighing ≥20 kg:
Mild to moderate impairment: No dosage adjustment necessary.
Severe impairment:
Weight 20 to <50 kg: Oral: Initial: 10 mg once daily in the morning on days 1 to 3, then increase dose to 20 mg once daily in the morning on day 4 and thereafter.
Weight ≥50 kg: Initial: Oral: 10 mg once daily in the morning on days 1 to 3, then increase dose to 20 mg once daily in the morning on days 4 and 5, then increase dose to 30 mg once daily in the morning on day 6 and thereafter.
Psoriasis, plaque (moderate to severe):
Children ≥6 years and Adolescents weighing ≥20 kg:
Mild to severe impairment: No dosage adjustment necessary.
GI effects such as diarrhea, nausea, and vomiting, including severe cases, have been reported (Ref). GI effects typically resolve with continued treatment within ~4 weeks (Ref); however, dose reduction or discontinuation may be necessary for severe symptoms.
Mechanism: Related to pharmacologic action; phosphodiesterase 4 (PDE4) inhibition and increased cyclic adenosine monophosphate levels lead to activation of membrane chloride channels and subsequent fluid secretion into the gut, causing diarrhea. PDE4 inhibition and increased cyclic adenosine monophosphate levels may also contribute to both central and peripheral mechanisms that lead to nausea (Ref).
Onset: Intermediate; usually within the first 2 weeks of initiation (Ref).
Risk factors (for complications from severe GI effects):
• Patients ≥65 years
• Patients taking medications that may lead to volume depletion or hypotension
Neuropsychiatric effects (eg, anxiety, depression, mood changes, suicidal ideation, suicidal tendencies) have been reported rarely with apremilast (Ref). In one cohort study of patients with psoriasis, users of apremilast had similar rates of anxiety plus depression as users of other noncorticosteroid systemic psoriasis treatments; however, the rate of anxiety was higher (Ref).
Onset: Varied; occurred within 2 years after initiation (Ref).
Risk factors:
• History of bipolar disorder, depression, and/or emotional or physical abuse (Ref)
Over 52 weeks or longer, the mean weight loss with apremilast in the clinical trial population was ~1% (Ref). Over 156 weeks, the mean weight loss was 1.5% (Ref). Weight loss >5% has been reported in 12% to 14% of patients in the first 24 weeks (Ref). Over follow-up at 3 to 5 years, 20% to 22% of patients lost >5% body weight (Ref).
Mechanism: Related to pharmacologic action; phosphodiesterase 4 inhibition increases secretion of glucagon-like-peptide-1, which stimulates insulin secretion and inhibits glucagon secretion (Ref).
Onset: Varied; within 1 year (Ref).
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults.
>10%:
Endocrine & metabolic: Weight loss (>5% of body weight: 5%; 5% to 10% of body weight: 10% to 12%; ≥10% of body weight: 2%) (table 1)
|
Drug (Apremilast) |
Placebo |
Dose |
Indication |
Number of Patients (Apremilast) |
Number of Patients (Placebo) |
Comments |
|---|---|---|---|---|---|---|
|
5% |
4% |
30 mg twice daily |
Behçet disease |
103 |
102 |
>5% of body weight |
|
12% |
5% |
30 mg twice daily |
Moderate to severe plaque psoriasis |
784 |
382 |
5% to 10% of body weight |
|
2% |
1% |
30 mg twice daily |
Moderate to severe plaque psoriasis |
784 |
382 |
≥10% of body weight |
|
10% |
3% |
30 mg twice daily |
Psoriatic arthritis |
497 |
495 |
5% to 10% of body weight |
Gastrointestinal: Diarrhea (8% to 41%; severe diarrhea: <1%) (table 2), nausea (7% to 22%; severe nausea: <1%) (table 3)
|
Drug (Apremilast) |
Placebo |
Dose |
Indication |
Number of Patients (Apremilast) |
Number of Patients (Placebo) |
Comments |
|---|---|---|---|---|---|---|
|
41% |
20% |
30 mg twice daily |
Behçet disease |
104 |
103 |
Up to week 12 |
|
17% |
6% |
30 mg twice daily |
Moderate to severe plaque psoriasis |
920 |
506 |
Up to day 112 |
|
9% |
1% |
30 mg twice daily |
Psoriatic arthritis |
497 |
495 |
Day 1 to day 5 |
|
8% |
2% |
30 mg twice daily |
Psoriatic arthritis |
493 |
490 |
Day 6 to day 112 |
|
Drug (Apremilast) |
Placebo |
Dose |
Indication |
Number of Patients (Apremilast) |
Number of Patients (Placebo) |
Comments |
|---|---|---|---|---|---|---|
|
19% |
11% |
30 mg twice daily |
Behçet disease |
104 |
103 |
Up to week 12 |
|
17% |
7% |
30 mg twice daily |
Moderate to severe plaque psoriasis |
920 |
506 |
Up to day 112 |
|
9% |
3% |
30 mg twice daily |
Psoriatic arthritis |
493 |
490 |
Day 6 to day 112 |
|
7% |
1% |
30 mg twice daily |
Psoriatic arthritis |
497 |
495 |
Day 1 to day 5 |
Nervous system: Headache (5% to 14%)
Respiratory: Upper respiratory tract infection (4% to 12%; viral upper respiratory tract infection: 7%)
1% to 10%:
Dermatologic: Folliculitis (1%)
Gastrointestinal: Abdominal pain (4%; upper abdominal pain: ≤9%), decreased appetite (3%), dyspepsia (3%), frequent bowel movements (2%), tooth abscess (1%), vomiting (0.8% to 9%; severe vomiting: <1%) (table 4)
|
Drug (Apremilast) |
Placebo |
Dose |
Indication |
Number of Patients (Apremilast) |
Number of Patients (Placebo) |
Comments |
|---|---|---|---|---|---|---|
|
9% |
2% |
30 mg twice daily |
Behçet disease |
104 |
103 |
Up to week 12 |
|
4% |
2% |
30 mg twice daily |
Moderate to severe plaque psoriasis |
920 |
506 |
Up to day 112 |
|
3% |
0.4% |
30 mg twice daily |
Psoriatic arthritis |
493 |
490 |
Day 6 to day 112 |
|
0.8% |
0.4% |
30 mg twice daily |
Psoriatic arthritis |
497 |
495 |
Day 1 to day 5 |
Nervous system: Depressed mood (≤1%), depression (≤1%; severe depression: <1%) (table 5), fatigue (3%), insomnia (2%), migraine (2%), tension headache (8%)
|
Drug (Apremilast) |
Placebo |
Indication |
Number of Patients (Apremilast) |
Number of Patients (Placebo) |
Comments |
|---|---|---|---|---|---|
|
1% |
1% |
Behçet disease |
104 |
103 |
Described as depression or depressed mood |
|
1% |
0.4% |
Moderate to severe plaque psoriasis |
920 |
506 |
N/A |
|
Severe depression: 0.1% |
0% |
Moderate to severe plaque psoriasis |
1,308 |
506 |
N/A |
|
1% |
0.8% |
Psoriatic arthritis |
998 |
495 |
Described as depression or depressed mood |
|
Severe depression: 0.2% |
0% |
Psoriatic arthritis |
1,441 |
495 |
Described as depression or depressed mood |
Neuromuscular & skeletal: Arthralgia (6%), back pain (2% to 8%)
Respiratory: Bronchitis (1%), nasopharyngitis (3%), sinus headache (1%)
<1%:
Dermatologic: Exacerbation of psoriasis (rebound following discontinuation)
Nervous system: Suicidal ideation (table 6), suicidal tendencies (table 7)
|
Drug (Apremilast) |
Placebo |
Indication |
Number of Patients (Apremilast) |
Number of Patients (Placebo) |
Comments |
|---|---|---|---|---|---|
|
0.2% |
0% |
Psoriatic arthritis |
1,441 |
495 |
Described as suicidal ideation and behavior |
|
Drug (Apremilast) |
Placebo |
Indication |
Number of Patients (Apremilast) |
Number of Patients (Placebo) |
Comments |
|---|---|---|---|---|---|
|
0.1% |
0.2% |
Moderate to severe plaque psoriasis |
1,308 |
506 |
N/A |
|
0.2% |
0% |
Psoriatic arthritis |
1,441 |
495 |
Described as suicidal ideation and behavior |
Frequency not defined:
Dermatologic: Skin rash
Gastrointestinal: Gastroesophageal reflux disease
Hypersensitivity: Hypersensitivity reaction
Respiratory: Cough
Postmarketing:
Hypersensitivity: Anaphylaxis, angioedema
Nervous system: Anxiety (Vasilakis-Scaramozza 2020)
Hypersensitivity to apremilast or any component of the formulation.
Canadian labeling: Additional contraindications (not in US labeling): Pregnancy; breastfeeding.
Disease-related concerns:
• Renal impairment: Use with caution in renal impairment. Systemic exposure is increased in patients with severe renal impairment (CrCl <30 mL/minute); dosage reduction is recommended.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Otezla: 30 mg
Tablet Therapy Pack, Oral:
Otezla: 10 & 20 & 30 mg (55 ea)
No
Tablet Therapy Pack (Otezla Oral)
10 & 20 & 30 mg (per each): $105.39
Tablets (Otezla Oral)
30 mg (per each): $96.61
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Otezla: 30 mg
Generic: 30 mg
Tablet Therapy Pack, Oral:
Otezla: 10 & 20 & 30 mg (27 ea)
Generic: 10 & 20 & 30 mg (27 ea)
Oral: Administer without regard to food. Do not crush, chew, or split tablets.
Oral: Administer without regard to food. Do not crush, chew, or split tablets.
Behçet disease: Treatment of adults with oral ulcers associated with Behçet disease.
Psoriasis: Treatment of adults with plaque psoriasis who are candidates for phototherapy or systemic therapy; treatment of pediatric patients ≥6 years of age and ≥20 kg with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy.
Psoriatic arthritis: Treatment of adults with active psoriatic arthritis.
Substrate of CYP3A4 (major), P-glycoprotein/ABCB1 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
COVID-19 Vaccines: Apremilast may diminish the therapeutic effect of COVID-19 Vaccines. Management: Rheumatology guidelines recommend holding apremilast for 1 to 2 weeks after vaccine administration as permitted by the underlying disease. These guidelines consider apremilast to be an immunomodulatory or immunosuppressive medication. Risk D: Consider therapy modification
CYP3A4 Inducers (Moderate): May decrease the serum concentration of Apremilast. Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May decrease the serum concentration of Apremilast. Risk X: Avoid combination
Riociguat: Apremilast may enhance the hypotensive effect of Riociguat. Management: Riociguat is contraindicated with nonselective phosphodiesterase (PDE) inhibitors and PDE type 5 inhibitors. Other types of PDE inhibitors are not contraindicated, but caution is advised and patients should be monitored for hypotension. Risk C: Monitor therapy
Based on data from animal reproduction studies, in utero exposure to apremilast may cause an increase in pregnancy loss. According to the manufacturer, pregnancy planning and prevention should be considered for patients who could become pregnant.
Recommendations for use of apremilast to treat rheumatic and musculoskeletal diseases in patients planning to become pregnant or patients who are planning to father a child are not available due to lack of data (ACR [Sammaritano 2020]).
Based on data from animal reproduction studies, in utero exposure to apremilast may cause an increase in pregnancy loss.
Recommendations for use of apremilast in pregnant patients with rheumatic and musculoskeletal diseases are not available due to lack of data. Placental transfer may be expected based on molecular weight (ACR [Sammaritano 2020]).
It is not known if apremilast is present in breast milk.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother. Recommendations for use of apremilast in breastfeeding patients with rheumatic and musculoskeletal diseases are not available due to lack of data. Transfer into breast milk may be expected based on molecular weight (ACR [Sammaritano 2020]).
Monitor weight regularly during therapy; growth (height/weight in pediatric patients); renal function; signs or symptoms of mood changes, depression, or suicidal thoughts; diarrhea or vomiting, especially patients more susceptible to complications of diarrhea (eg, older patients, patients taking medications that may lead to volume depletion or hypotension).
Apremilast inhibits phosphodiesterase 4 (PDE4) specific for cyclic adenosine monophosphate (cAMP) which results in increased intracellular cAMP levels and regulation of numerous inflammatory mediators (eg, decreased expression of nitric oxide synthase, TNF-α, and interleukin [IL]-23, as well as increased IL-10) (Schafer, 2012).
Absorption: Well absorbed
Distribution: Vd: 87 L
Protein binding: ~68%
Metabolism: Hepatic, primarily via CYP3A4: minor pathways include CYP1A2 and CYP2A6
Bioavailability: ~73%
Half-life elimination: ~6 to 9 hours
Time to peak: ~2.5 hours
Excretion: Urine (58%; 3% unchanged drug); feces (39%; 7% unchanged drug)
Altered kidney function: The AUC and Cmax of apremilast increased by ~88% and 42%, respectively, in patients with severe renal impairment.
Older adult: The apremilast exposure in elderly subjects (65 to 85 years of age) was about 13% higher in AUC and about 6% higher in Cmax than in younger subjects (18 to 55 years of age).
Sex: The extent of exposure in females was about 31% higher and Cmax was about 8% higher than that in male subjects.
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