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Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Otezla: 30 mg
Tablet Therapy Pack, Oral:
Otezla: 10 & 20 & 30 mg (27 ea [DSC], 55 ea)
Brand Names: U.S.
- Phosphodiesterase-4 Enzyme Inhibitor
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).
Vd: 87 L
Hepatic, primarily via CYP3A4: minor pathways include CYP1A2 and CYP2A6
Urine (58%; 3% unchanged drug); feces (39%; 7% unchanged drug)
Time to Peak
~6 to 9 hours
Special Populations: Renal Function Impairment
The AUC and Cmax of apremilast increased by ~88% and 42%, respectively, in patients with severe renal impairment.
Special Populations: Elderly
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).
Special Populations: Gender
The extent of exposure in females was about 31% higher and Cmax was about 8% higher than that in male subjects.
Use: Labeled Indications
Psoriasis: Treatment of patients with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy
Psoriatic arthritis: Treatment of adult patients with active psoriatic arthritis (PsA)
Hypersensitivity to apremilast or any component of the formulation
Canadian labeling: Additional contraindications (not in US labeling): Pregnancy; breast-feeding
Active psoriatic arthritis or plaque psoriasis (moderate to severe): Oral: Initial: 10 mg in the morning. 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
Refer to adult dosing.
Dosing: Renal Impairment
CrCl <30 mL/minute: Initial: 10 mg in the morning on days 1 to 3; titrate using morning doses only (skip evening doses) to 20 mg on days 4 and 5. Maintenance dose: 30 mg once daily in the morning starting on day 6.
Dosing: Hepatic Impairment
No dosage adjustment necessary.
Oral: Administer without regard to food. Do not crush, chew, or split tablets.
Store below 30°C (86°F).
Bosentan: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
CYP3A4 Inducers (Strong): May decrease the serum concentration of Apremilast. Avoid combination
Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates. Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
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. Monitor therapy
Siltuximab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
St John's Wort: May decrease the serum concentration of CYP3A4 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Frequency not always defined.
Central nervous system: Tension headache (7%), headache (6%), fatigue (3%), depression (2%), insomnia (2%), migraine (2%), paresthesia (<2%)
Dermatologic: Skin rash (<2%), folliculitis (1%)
Endocrine & metabolic: Weight loss (≥5% of body weight: 19%; ≥10% of body weight: 6%)
Gastrointestinal: Diarrhea (18%), nausea (17%), vomiting (4%), decreased appetite (3%), dyspepsia (3%), abdominal distress (2%), abdominal pain (2%), frequent bowel movements (2%), upper abdominal pain (2%), abdominal distention (<2%), gastroesophageal reflux disease (<2%)
Hypersensitivity: Hypersensitivity (<2%)
Infection: Influenza (<2%), tooth abscess (1%)
Neuromuscular & skeletal: Back pain (2%), arthralgia (<2%), muscle spasm (<2%), myalgia (<2%)
Respiratory: Upper respiratory tract infection (8%), nasopharyngitis (7%), sinusitis (2%), bronchitis (<2%), cough (<2%), pharyngitis (<2%), rhinitis (<2%), sinus headache (<2%)
<1% (Limited to important and life-threatening): Atrial fibrillation, exacerbation of psoriasis (rebound following discontinuation), tachyarrhythmia
Concerns related to adverse effects:
• 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.
• 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.
Concurrent drug therapy issues:
• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
Monitor weight regularly during therapy; renal function; signs or symptoms of mood changes, depression, or suicidal thoughts
Pregnancy Risk Factor
Adverse events were observed in some animal reproduction studies. A registry is available for women exposed to apremilast during pregnancy (877-311-8972). The Canadian labeling contraindicates use during pregnancy and recommends women attempting to conceive avoid use.
• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience headache, diarrhea, or nausea. Have patient report immediately to prescriber signs of depression (suicidal ideation, anxiety, emotional instability, or confusion), excessive weight loss, agitation, irritability, panic attacks, or mood changes (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.
More about apremilast
- Other brands: Otezla