APREMILAST
Clinical safety rating: avoid
Contraindicated (not allowed)
Apremilast is a small-molecule inhibitor of phosphodiesterase 4 (PDE4), which leads to increased intracellular levels of cyclic adenosine monophosphate (cAMP). This modulates the production of pro-inflammatory and anti-inflammatory cytokines, resulting in decreased expression of TNF-α, IL-23, and other inflammatory mediators, and increased IL-10.
| Metabolism | Apremilast is extensively metabolized primarily by CYP3A4, with minor contributions from CYP1A2 and CYP2A6. The major metabolic pathways include glucuronidation and oxidation. It is also a substrate of CYP3A4 and P-glycoprotein. |
| Excretion | 58% renal (39% as unchanged drug, 19% as metabolites), 39% fecal (9% as unchanged drug, 30% as metabolites). Total recovery 97%. |
| Half-life | 6-9 hours (mean ~6.5 h) in healthy adults; no clinically significant accumulation with once-daily dosing. |
| Protein binding | Approximately 99% bound to human plasma proteins, primarily albumin. |
| Volume of Distribution | Mean Vd/F ~87 L (~1.2 L/kg for a 70 kg individual), indicating extensive distribution into tissues. |
| Bioavailability | Oral bioavailability ~73% (absolute); not significantly affected by food, but administration with food reduces peak concentration by ~40% without altering AUC. |
| Onset of Action | Oral: Clinical improvement in Psoriasis may be observed as early as 2 weeks, with maximal effect typically by 16-24 weeks. |
| Duration of Action | Duration of therapeutic effect is sustained with continued dosing; after discontinuation, relapse occurs over weeks to months (median time to loss of PASI-75 response ~12 weeks). |
30 mg orally twice daily, after an initial titration: 10 mg in the morning on day 1, 10 mg in the morning and evening on day 2, 10 mg in the morning and 20 mg in the evening on day 3, 20 mg in the morning and 20 mg in the evening on day 4, 20 mg in the morning and 30 mg in the evening on day 5, then 30 mg twice daily thereafter.
| Dosage form | TABLET |
| Renal impairment | For severe renal impairment (eGFR <30 mL/min/1.73 m²), reduce dose to 30 mg once daily. For end-stage renal disease (eGFR <15 mL/min/1.73 m²) or on dialysis, use 30 mg once daily; consider dose reduction if inadequate response. |
| Liver impairment | For moderate to severe hepatic impairment (Child-Pugh B or C), reduce dose to 30 mg once daily. No adjustment needed for mild impairment (Child-Pugh A). |
| Pediatric use | Not approved for pediatric use; safety and efficacy not established. |
| Geriatric use | No specific dose adjustment required based on age alone. However, due to higher risk of renal impairment, assess renal function and adjust accordingly; monitor for gastrointestinal effects and weight loss. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Strong CYP450 inducers (eg rifampin) reduce apremilast exposure May cause weight loss and depression monitor patient accordingly.
| Breastfeeding | Excreted in rat milk; unknown in humans. M/P ratio not available. Consider benefit vs risk; manufacturer advises discontinue nursing or drug due to potential for serious adverse reactions in infant. |
| Teratogenic Risk | Animal studies show fetal toxicity (reduced fetal weight, skeletal variations) at doses ≥2 times MRHD. No adequate human studies. Avoid in 2nd and 3rd trimesters due to potential risk of low birth weight and preterm delivery. FDA Pregnancy Category C. |
■ FDA Black Box Warning
None.
| Common Effects | psoriatic arthritis |
| Serious Effects |
["Known hypersensitivity to apremilast or any component of the formulation","Coadministration with strong CYP3A4 inducers (e.g., rifampin, phenytoin, carbamazepine, phenobarbital, St. John's wort) due to potential loss of efficacy"]
| Precautions | ["Depression and suicidal ideation: Patients should be monitored for mood changes, depression, and suicidal thoughts.","Weight loss: Monitor weight regularly; consider discontinuation if unexplained or clinically significant weight loss occurs.","Diarrhea, nausea, and vomiting: Most common adverse reactions, may lead to dehydration; assess risk in patients on medications that may cause volume depletion.","Drug interactions: Strong CYP3A4 inducers (e.g., rifampin) reduce apremilast exposure and may decrease efficacy; coadministration with strong CYP3A4 inducers is not recommended.","Renal impairment: Dosage adjustment is required for patients with severe renal impairment (CrCl < 30 mL/min)."] |
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| Fetal Monitoring |
| Monitor for depression, suicidal ideation, and GI intolerance. In pregnancy, monitor fetal growth and development via ultrasound. Assess for signs of infection due to potential immunosuppression. |
| Fertility Effects | In animal studies, no impairment of male or female fertility at exposures up to 3 times MRHD. Human data lacking. Potential for reduced fertility due to associated depression or GI effects. |
| Food/Dietary | Avoid grapefruit and grapefruit juice, as they may inhibit CYP3A4 and increase apremilast exposure. No other significant food interactions. Take with or without food; taking with food may reduce GI upset. |
| Clinical Pearls | Apremilast is a PDE4 inhibitor used for psoriasis and psoriatic arthritis. It does not require routine laboratory monitoring. Dose adjustment needed in severe renal impairment (CrCl <30 mL/min): reduce to 30 mg once daily. Initial dose titration over 5 days reduces GI side effects. Contraindicated in pregnancy due to potential harm (PDE4 inhibition linked to fetal abnormalities). May cause weight loss; monitor weight regularly. Avoid in patients with depression or suicidal ideation as neuropsychiatric events have been reported. |
| Patient Advice | Take medication exactly as prescribed with or without food. · Initiate treatment with a starter pack to gradually increase dose over 5 days to reduce nausea and diarrhea. · Do not drink grapefruit juice or eat grapefruit as it may increase drug levels. · Report any worsening depression, suicidal thoughts, or mood changes immediately. · Tell your doctor if you have kidney problems, as dose adjustment may be needed. · Apremilast can cause weight loss; monitor your weight and report significant changes. · Use effective contraception during treatment and for at least 4 weeks after stopping if female of childbearing potential. · Avoid alcohol as it may worsen side effects like dizziness or gastrointestinal upset. |