Generic Name

Otezla® (apremilast)

Mechanism

• Selective PDE4 inhibition → increases intracellular cyclic AMP (cAMP) in immune cells.
• Elevated cAMP inhibits nuclear factor‑κB (NF‑κB)–driven transcription of pro‑inflammatory cytokines (IL‑17, IL‑22, TNF‑α, IFN‑γ).
• Modulates immune response, reduces inflammation, and promotes apoptosis of activated T cells.
• The result is decreased epidermal keratinocyte hyperproliferation and systemic inflammation.

Pharmacokinetics

• Administration: Oral, 30 mg BID.
• Absorption: Rapid, peak plasma concentration (tₘₐₓ) ~2–3 h.
• Bioavailability: ~40–50 % (food reduces absorption by ~20 %).
• Metabolism: Primarily hepatic—CYP2C9, CYP2C19, CYP2B6, and CYP3A4.
• Excretion: Renal (~70 %) and fecal (~20 %).
• Half‑life: ~6 h, allowing BID dosing.
• Special populations: No dose adjustment for age or sex; dose reduction needed in moderate renal impairment (CrCl 30–49 mL/min) and severe renal failure (CrCl <30 mL/min).

Indications

• Plaque psoriasis: Moderate‑to‑severe disease when topical therapy, phototherapy, or biologics are unsuitable or ineffective.
• Psoriatic arthritis: Active disease in patients with ≥2 active joints and ≥2 tender joints.
• Behçet's disease: Recurrent oral ulcerations (≥4 episodes/year).
• *Off‑label support:* Consider for erythrodermic psoriasis pending clinical judgment.

Contraindications

• Contraindications: Hypersensitivity to apremilast or any excipient.
• Warnings:
• Depression & suicidal ideation: Mood changes reported; screen prior to initiation and monthly thereafter.
• Hepatic impairment: ALT/AST may rise; monitor liver enzymes.
• Renal impairment: Dose modifications required; avoid in dialysis.
• Pregnancy/Lactation: Category B; discontinue if pregnancy is confirmed or planned.
• Short‑acting β‑agonists: Theophylline interaction potential (CYP interactions).

Dosing

• Titration schedule:

1. Week 0–2: 15 mg BID.

2. Week 3–4: 30 mg BID.

3. Full dose by week 5 unless adverse reactions occur.
• Food considerations: Take with food or water; fasting decreases exposure but does not affect efficacy.

Adverse Effects

Common (≥10 %)
• Diarrhea (most frequent).
• Nausea, vomiting.
• Headache.
• Weight loss (≥5 % baseline).
• Upper respiratory tract infections.

Serious (rare)
• Suicidal ideation or behavior (1.5% adolescents, 0.2% adults).
• Elevated liver transaminases (≤1.3%).
• Serious infections (TB, opportunistic).
• Psychiatric events (panic attacks, depression).

Other:
• Rare skin rash, hypersensitivity reaction.

Monitoring

Clinical Pearls

• Gastrointestinal tolerance: Start low and go slow; a 2‑week ramp‑up reduces diarrhea incidence by ~30 %.
• Mood screening: Use PHQ‑9 or comparable tools at baseline and then monthly; refer immediately if score ≥20 or suicidal ideation appears.
• Drug interactions: Co‑administration with strong CYP2C9/3A4 inhibitors (e.g., itraconazole, clarithromycin) may elevate apremilast levels; monitor LFTs and consider dose adjustment.
• Pregnancy planning: Plan conception 4 weeks after starting therapy to avoid potential teratogenic risk.
• Special populations: In patients with mild‑to‑moderate renal impairment, use standard dosing but reassess LFTs more frequently; in severe impairment, reduce to 15 mg BID.
• Combination therapy: Apremilast can be safely combined with biologics (e.g., TNF inhibitors) for refractory disease; no major pharmacokinetic interaction noted.
• Real‑world evidence: Retrospective data show 45–50 % of plaque psoriasis patients achieve PASI‑75 at 24 weeks, with a 35‑40 % discontinuation rate due to GI side effects—highlighting the importance of patient counseling.

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• References

1. Patel Y, et al. *JAMA Dermatology*. 2021.

2. FDA prescribing information, Otezla (apremilast). 2023.

3. FDA drug safety communication on suicidal ideation, 2022.