1. Clinical Overview
Apremilast is an oral, small-molecule inhibitor of phosphodiesterase 4 (PDE4) used in the management of moderate to severe plaque psoriasis and active psoriatic arthritis. It modulates intracellular inflammatory pathways by increasing cyclic AMP (cAMP) levels, leading to downregulation of pro-inflammatory mediators like TNF-α, IL-17, and IL-23, and upregulation of anti-inflammatory mediators like IL-10. It is a targeted synthetic disease-modifying antirheumatic drug (tsDMARD).
| Onset | Duration | Bioavailability |
|---|---|---|
| Clinical improvement in symptoms (e.g., pruritus) may be seen within 2-4 weeks. Full therapeutic effect for psoriasis is typically observed by 16-24 weeks. | Approximately 24 hours, supporting once-daily dosing after titration. | Approximately 73%. |
2. Mechanism of Action
Apremilast selectively inhibits the intracellular enzyme phosphodiesterase 4 (PDE4). Inhibition of PDE4 results in increased intracellular levels of cyclic adenosine monophosphate (cAMP). Elevated cAMP activates protein kinase A (PKA), which subsequently phosphorylates and inhibits key transcription factors like nuclear factor kappa B (NF-κB). This leads to a net downregulation of pro-inflammatory cytokine production (e.g., TNF-α, IL-17, IL-23, IFN-γ) and an upregulation of anti-inflammatory cytokines (e.g., IL-10).
3. Indications & Uses
- Moderate to Severe Plaque Psoriasis in adults who are candidates for systemic therapy or phototherapy.
- Active Psoriatic Arthritis in adults.
4. Dosage & Administration
Adult Dosage: For Psoriasis/Psoriatic Arthritis: Titrate to 30 mg twice daily. Day 1: 10 mg AM. Day 2: 10 mg AM & PM. Day 3: 10 mg AM & 20 mg PM. Day 4: 20 mg AM & PM. Day 5: 20 mg AM & 30 mg PM. Day 6 onwards: 30 mg twice daily. The 20mg tablet is a step in titration and can be used as maintenance dose in renal impairment.
Administration: Can be taken with or without food. Swallow tablet whole with water. Do not crush, split, or chew. Adherence to the titration schedule is crucial to minimize GI side effects.
5. Side Effects
Common side effects may include:
- Diarrhea (occurring in ~17-19% of patients)
- Nausea (~15-17%)
- Headache (~10-12%)
- Upper Respiratory Tract Infection
- Vomiting
- Nasopharyngitis
- Abdominal discomfort
- Decreased appetite
6. Drug Interactions
| Drug | Effect | Severity |
|---|---|---|
| Strong CYP450 Inducers (e.g., Rifampicin, Carbamazepine, Phenytoin, Phenobarbital, St. John's Wort) | Significantly decrease apremilast exposure (AUC reduced by ~72%). May lead to loss of efficacy. | Major - Contraindicated or requires alternative therapy. |
| Strong CYP450 Inhibitors (e.g., Ketoconazole, Itraconazole, Clarithromycin, Ritonavir) | May increase apremilast exposure. Clinical significance unknown, but monitoring for side effects advised. | Moderate - Use with caution. |
7. Patient Counselling
- DO follow the exact titration schedule provided by your doctor to reduce stomach upset.
- DO report any new or worsening feelings of depression, anxiety, sadness, or suicidal thoughts immediately.
- DO inform all your doctors and pharmacists that you are taking apremilast.
- DO maintain adequate hydration, especially if experiencing diarrhea.
- DONT stop taking the medicine suddenly without consulting your doctor.
- DONT take with strong herbal remedies like St. John's Wort.
- DONT crush, chew, or split the tablet.
8. Toxicology & Storage
Overdose: Expected to be an extension of its pharmacological effects: severe nausea, vomiting, diarrhea, headache, dizziness, possibly hypotension.
Storage: Store at or below 30°C. Protect from moisture. Keep in the original blister pack or container. Keep out of reach of children.