1. Clinical Overview
Apremilast is a novel, orally administered small-molecule inhibitor of phosphodiesterase 4 (PDE4). It modulates intracellular cyclic adenosine monophosphate (cAMP) levels, leading to a downregulation of pro-inflammatory mediators and an upregulation of anti-inflammatory mediators. It is specifically indicated for the treatment of active psoriatic arthritis (PsA) and moderate to severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy.
| Onset | Duration | Bioavailability |
|---|---|---|
| Clinical improvement in symptoms (e.g., joint pain, skin lesions) may be observed as early as 2-4 weeks, with maximal response typically seen by 16-24 weeks of continuous therapy. | The pharmacodynamic effects are sustained with daily dosing. Upon discontinuation, symptoms may return within a few weeks. | Approximately 73% following oral administration. |
2. Mechanism of Action
Apremilast selectively inhibits the intracellular enzyme phosphodiesterase 4 (PDE4). Inhibition of PDE4 results in increased levels of cyclic adenosine monophosphate (cAMP) within immune cells (e.g., neutrophils, monocytes, T-cells). Elevated cAMP activates protein kinase A (PKA), which subsequently phosphorylates and inhibits key transcription factors like Nuclear Factor kappa B (NF-κB).
3. Indications & Uses
- Active Psoriatic Arthritis (PsA) in adults
- Moderate to Severe Plaque Psoriasis in adults who are candidates for systemic therapy or phototherapy
4. Dosage & Administration
Adult Dosage: For PsA and Plaque Psoriasis: Recommended maintenance dose is 30 mg twice daily. MUST BE TITRATED: Day 1: 10 mg AM. Day 2: 10 mg AM and PM. Day 3: 10 mg AM and 20 mg PM. Day 4: 20 mg AM and PM. Day 5: 20 mg AM and 30 mg PM. Day 6 and onward: 30 mg twice daily. The 10mg tablet is primarily used for this titration.
Administration: Can be taken with or without food. Swallow the tablet whole with water. Do not crush, split, or chew. If a dose is missed, take it as soon as remembered, then resume the normal schedule. Do not take two doses to make up for a missed dose.
5. Side Effects
Common side effects may include:
- Diarrhea (occurring in ~15-20% of patients, often during titration)
- Nausea (~10-15%)
- Headache (~8-10%)
- Upper respiratory tract infection
- Vomiting
- Nasopharyngitis
- Abdominal pain
- 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), potentially reducing efficacy. | Major |
| Strong CYP450 Inhibitors (e.g., Ketoconazole, Itraconazole, Clarithromycin, Ritonavir) | May increase apremilast exposure. However, no dosage adjustment is recommended as the increase is not clinically significant. | Moderate |
| Other Immunosuppressants/Therapy (e.g., Methotrexate, Biologics) | Concomitant use may increase risk of infections. Used together in clinical practice with monitoring, but not routinely recommended without specialist supervision. | Moderate |
7. Patient Counselling
- DO follow the exact titration schedule provided by your doctor to minimize stomach upset.
- DO take the tablet with food if you experience nausea.
- DO report any new or worsening feelings of sadness, anxiety, hopelessness, or suicidal thoughts to your doctor immediately.
- DO monitor your body weight regularly (e.g., weekly) and inform your doctor of significant or unintended weight loss.
- DONT stop taking apremilast suddenly without consulting your doctor, as symptoms may return.
- DONT crush, chew, or split the tablet.
- DONT start any new medication, including over-the-counter drugs or herbal supplements (like St. John's Wort), without informing your doctor.
8. Toxicology & Storage
Overdose: In clinical trials, single doses up to 100 mg have been administered without severe effects. Symptoms of overdose are expected to be an extension of its pharmacological and adverse effects: severe nausea, vomiting, diarrhea, headache, dizziness, and possibly hypotension.
Storage: Store at room temperature (15°C to 30°C). Protect from moisture. Keep in the original blister pack until use. Keep out of reach of children.