Fasenra
Fasenra
Generic Name
Fasenra
Mechanism
- IL‑4Rα blockade: Dupilumab binds to the extracellular domain of IL‑4Rα, preventing heterodimerization with the common mu chain (γc) or the 2B4 chain necessary for IL‑4 and IL‑13 receptor complex formation.
- Down‑regulation of Th2 cytokine signaling: Inhibits ST2‑dependent cell activation, reduces eosinophil recruitment, drives IgE class switching, and attenuates keratinocyte‑derived chemokines.
- Result: Decreases inflammation and pruritus in atopic dermatitis, airway hyperresponsiveness in asthma, and polyp tissue remodeling in CRSwNP.
Pharmacokinetics
| Parameter | Dupilumab (Fasenra) | |
| Administration | Subcutaneous injection | |
| Dosing | 2 × 150 mg (300 mg) on Day 0, Day 14, then q2 wk (atopic dermatitis), q4 wk (asthma) | |
| Absorption | Tmax ≈ 24 h; 93 % of administered dose recovered in plasma | |
| Bioavailability | 59 % | |
| Half‑life | 17–21 days (steady‑state ~15 days) | |
| Metabolism | Proteolytic cleavage to peptides; no CYP interactions | |
| Elimination | Renal & biliary routes via catabolism; no dose adjustment for renal/hepatic impairment |
Indications
- Atopic Dermatitis (AD) – adults & adolescents ≥12 yrs (≥30 kg); children ≥6 yrs (≥15 kg).
- Uncontrolled Asthma – adults, adolescents, and children ≥6 yrs with ≥1 exacerbation/year or requiring ≥2 controller meds.
- Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) – adults, adolescents ≥12 yrs, weight ≥30 kg.
Contraindications
- Allergy: Hypersensitivity to dupilumab or any excipient.
- Active infections: Severe viral, bacterial, or fungal infections may worsen; consider temporary discontinuation.
- Eosinophilic conditions: Severe uncontrolled eosinophilic granulomatosis with polyangiitis; monitor eosinophil counts; high risk of eosinophil‑driven organ damage.
- Pregnancy/Lactation: Category C; data insufficient; consider risk/benefit.
- Concurrent systemic immunosuppressive therapy: Use cautiously; may increase infection risk.
Warnings
• Ocular surface disease: Conjunctivitis, blepharitis, episcleritis, or keratitis may arise; early ophthalmology evaluation recommended.
• Vaccinations: Live vaccines contraindicated until at least 6 months after last dose.
• Influenza: Consider annual vaccination.
Dosing
| Condition | Loading Dose | Maintenance Dose | Frequency | Units |
| Atopic Dermatitis | 300 mg (2 × 150 mg) | 300 mg | Every 2 weeks | Subcutaneous |
| Asthma (≥12 yrs) | 400 mg (2 × 200 mg) | 200 mg | Every 4 weeks | Subcutaneous |
| Asthma (6‑12 yrs) | 200 mg (2 × 100 mg) | 100 mg | Every 4 weeks | Subcutaneous |
| CRSwNP | 200 mg (2 × 100 mg) | 200 mg | Every 4 weeks | Subcutaneous |
• Self‑injection training: Rotate injection sites (abdomen, thigh, upper arm).
• Premedication: Not routinely required; antihistamines may be used for first‑time injection site reactions.
• Storage: 2–8 °C; not for injection until just before use (room temp ≤25 °C).
Adverse Effects
- Injection‑site reactions: Erythema, pruritus, pain (30–70 %); mild to moderate.
- Ocular events: Conjunctivitis (5–15 %), blepharitis, corneal involvement.
- Upper respiratory infections: 5–10 % (cold/flu).
- Headache: 2–5 %.
- Eosinophilia: ↑ peripheral eosinophils ≤10 % of lymphocytes; monitor.
- Rare serious events:
- Severe hypersensitivity/anaphylaxis (0.15 %); treat with epinephrine, antihistamines, steroids.
- Venous thromboembolism: ↑ risk in predisposed patients.
- Bullous pemphigoid: Autoimmune epidermal blistering (rare).
- Invasive fungal infections: Require evaluation.
Monitoring
- Baseline: CBC with diff (eosinophils), LFTs, CRP, serum IgE, ocular examination.
- During therapy:
- CBC w/ diff every 4 weeks first 3 months, then q3 months.
- Serum IgE q6–12 months if immunogenicity suspected.
- LFTs q6–12 months.
- Ocular exam: baseline, 4 wk, then every 3 months.
- Clinical evaluation: Assess PASI, EASI, or ACT scores in AD; ACT‑QOL in asthma; nasal polyp score in CRSwNP.
Clinical Pearls
- Dual‑indication advantage: Patients with comorbid asthma & atopic dermatitis benefit from a single biologic; monitor both disease activity.
- Early ocular surveillance: Initiate baseline eye exam; educate patients to report redness, pain, or visual changes; prompt ophthalmological intervention can prevent vision loss.
- Eosinophil monitoring: A rise >1500 /µL warrants evaluation for eosinophilic disorders; consider dose adjustment or discontinuation.
- Vaccination strategy: Administer inactivated vaccines before starting Fasenra whenever possible; defer live vaccines for ≥6 months post‑last dose.
- Adolescent dosing: Use weight‑based (≥12 yrs) dose 200 mg every 4 wk; confirm puberty status to avoid potential infertility concerns.
- Pregnancy counseling: Limited data; many clinicians elect to pause therapy during conception, pregnancy, and lactation after risk‑benefit assessment.
- Adherence tip: Recommend the same time of day for injections to reinforce routine; use a phone reminder system.
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• *This drug card compiles evidence‑based, current prescribing data for Fasenra (dupilumab) and is intended for medical students, residents, and practicing clinicians seeking concise, yet holistic guidance.*