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.
Refer to adult dosing.
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
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.
Behçet disease: Treatment of oral ulcers associated with Behçet disease.
Psoriasis: Treatment of patients with plaque psoriasis who are candidates for phototherapy or systemic therapy.
Psoriatic arthritis: Treatment of patients with active psoriatic arthritis.
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%)
Gastrointestinal: Diarrhea (8% to 41%; severe diarrhea: <1%), nausea (7% to 22%; severe nausea: <1%)
Nervous system: Headache (5% to 14%; severe headache: <1%)
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%; severe abdominal pain: <1%), decreased appetite (3%), dyspepsia (3%), frequent bowel movements (2%), vomiting (≤9%; severe vomiting: <1%)
Infection: Tooth abscess (1%)
Nervous system: Depressed mood (≤1%), depression (≤1%; severe depression: <1%), fatigue (3%), insomnia (2%), migraine (2%), tension headache (8%)
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, suicidal tendencies
Frequency not defined:
Dermatologic: Skin rash
Gastrointestinal: Gastroesophageal reflux disease
Hypersensitivity: Hypersensitivity reaction
Respiratory: Cough
Postmarketing: Hypersensitivity: Anaphylaxis, angioedema
Hypersensitivity to apremilast or any component of the formulation.
Canadian labeling: Additional contraindications (not in US labeling): Pregnancy; breastfeeding.
Concerns related to adverse effects:
• GI effects: Severe diarrhea, nausea, and vomiting have been reported, usually observed within the first few weeks of initiating therapy. Monitor patients who are more susceptible to complications of diarrhea or vomiting; use with caution in elderly patients (≥65 years) and patients taking medications that may lead to volume depletion or hypotension. Symptom improvement observed with dose reduction or discontinuation of therapy; consider dose reduction or suspension of therapy if severe symptoms occur.
• Hypersensitivity: Hypersensitivity reactions (eg, anaphylaxis, angioedema) have been reported. Discontinue treatment and institute appropriate therapy if hypersensitivity occurs.
• Neuropsychiatric effects: Neuropsychiatric effects (eg, depression, suicidal ideation, mood changes) have been reported. Use with caution in patients with a history of depression and/or suicidal thoughts /behavior. Instruct patients/caregivers to report worsening psychiatric symptoms and consider risks/benefits of continuation of therapy in such patients.
• Weight loss: May cause weight loss; monitor weight regularly. Discontinuation of therapy should be considered with unexplained or significant weight loss.
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.
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 Lexicomp 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 females of reproductive potential.
Recommendations for use of apremilast to treat rheumatic and musculoskeletal diseases in females who are planning a pregnancy or males 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]).
Data collection to monitor pregnancy and infant outcomes following exposure to apremilast is ongoing. A registry is available for women exposed to apremilast during pregnancy (1-877-311-8972).
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; renal function; signs or symptoms of mood changes, depression, or suicidal thoughts
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.
Tablet Therapy Pack (Otezla Oral)
10 & 20 & 30 mg (per each): $94.78
Tablets (Otezla Oral)
30 mg (per each): $86.88
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.
