Generic Name

Levocetirizine

Mechanism

• Selective antagonism of peripheral H1 receptors on vascular endothelium, mast cells, and nerve endings → ↓ histamine‑mediated itching, wheal formation, and vasodilation.
• High affinity and slow dissociation (≈ 7 h) yields a sustained 24‑h duration.
• **No significant μ‑receptor or α‑adrenergic activity thus limited CNS penetration and negligible hypotension or mydriasis.

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Pharmacokinetics

• Absorption: Rapid oral absorption; peak plasma concentration ~2–3 h.
• Bioavailability: ~56 % (dose linear from 0.5–10 mg).
• Distribution: Volume of distribution ≈ 10 L (low protein binding ~20 %).
• Metabolism: Minimal hepatic metabolism (≈ 15 %), primarily via CYP3A4 (minor contribution).
• Elimination: 70 % renal excretion unchanged; remaining eliminated via hepatic pathways.
• Half‑life: ~8–10 h; prolonged to ~10–12 h in renal impairment.
• Special populations:
• *Renal impairment:* Dose adjustment required; renal clearance reduces half‑life.
• *Hepatic impairment:* No clinically relevant dose modification.
• *Pregnancy:* Category B; animal studies show no teratogenicity.

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Indications

• Chronic idiopathic urticaria (≥6 weeks).
• Seasonal or perennial allergic rhinitis (nasal congestion, rhinorrhea, sneezing, pruritus).
• Dermatitis and pruritus secondary to allergic exposure (with or without wheals).
• Allergic conjunctivitis when histamine release is a primary driver.

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Contraindications

• Contraindicated in patients with known hypersensitivity to levocetirizine or any excipient.
• Warnings
• Renal impairment (CrCl < 30 mL/min): monitor for accumulation, consider 2.5 mg q12h or prolonged dosing intervals.
• Elderly: increased risk of dizziness; cautious titration.
• Pregnancy & Lactation: Category B; normally safe but consider risk‑benefit.
• Medullary thyroid carcinoma: not contraindicated, but lack of evidence in MEN2A risk.
• Concomitant use with monoamine oxidase inhibitors (MAO‑I) or drugs that inhibit CYP3A4 may modestly raise levocetirizine levels; generally well tolerated.

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Dosing

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Adverse Effects

• Common (≥5 %):
• Headache, fatigue, dry mouth, drowsiness (rare).
• Indigestion, nausea, blurred vision.
• Serious (rare):
• Severe allergic reactions (anaphylaxis).
• QT interval prolongation (rare, with overdose).
• Liver enzyme elevation (monitor in hepatic disease).
• Post‑marketing reports: rare reports of “treatment‑emergent dysphoria” or mood changes in adolescents; consider counseling.

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Monitoring

• Baseline: serum creatinine, eGFR.
• Follow‑up:
• Renal function every 4–6 weeks if CrCl < 60 mL/min.
• Liver enzymes if hepatic comorbidity or drug interactions.
• Clinical response (pruritus score, nasal congestion diary).
• Re‑evaluation after dose change or in case of adverse events: check for efficacy vs sedation.

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Clinical Pearls

• Non‑sedating advantage: Levocetirizine is 98 % CNS‑impermeable, making it preferable for patients requiring alertness (e.g., shift workers, patients on psychotropics).
• Low interaction profile: Minimal CYP450 involvement—rarely displaces or disinhibits other drugs. Ideal for polypharmacy regimens.
• Elderly dosing: Start at 2.5 mg; titrate to 5 mg only if symptoms persist; watch for increased postural hypotension when combined with antihypertensives.
• Pediatric use: Pharmacokinetics similar to adults; the dose per kg is lower; ensure proper liquid vaccination forms to avoid ingestion errors.
• PERIODICAL over‑excretion risk: In patients with <30 mL/min CrCl, a single daily dose of 2.5 mg is usually effective and safe; double‑dosing can lead to accumulation and mild sedation.

These pearls help clinicians choose levocetirizine safely and effectively across age groups and comorbidities.