Introduction
Cetirizine is a second-generation antihistamine medication widely used for the management of allergic conditions. As a selective H1-receptor antagonist, it represents a significant advancement over first-generation antihistamines due to its improved safety profile and reduced sedative effects. First approved by the FDA in 1995, cetirizine has become a mainstay in the treatment of various allergic disorders.
Mechanism of Action
Cetirizine competitively antagonizes histamine at peripheral H1 receptors. Unlike first-generation antihistamines, it has minimal affinity for cholinergic, adrenergic, or serotonin receptors, resulting in fewer anticholinergic side effects. The drug inhibits histamine-mediated early phase allergic responses and may also suppress eosinophil chemotaxis and expression of adhesion molecules, providing anti-inflammatory effects beyond simple histamine blockade.
Indications
- Perennial and seasonal allergic rhinitis
- Chronic idiopathic urticaria
- Allergic conjunctivitis (off-label)
- Atopic dermatitis (as adjunctive therapy)
- Mild allergic skin reactions
Dosage and Administration
Adults and children ≥12 years: 5-10 mg orally once daily Children 6-11 years: 5-10 mg orally once daily (5 mg recommended starting dose) Children 2-5 years: 2.5-5 mg orally once daily (2.5 mg recommended starting dose) Renal impairment (CrCl 11-31 mL/min): 5 mg orally once daily Hepatic impairment: 5 mg orally once daily Elderly: Consider reduced dosing if renal impairment presentPharmacokinetics
Absorption: Rapidly absorbed with peak plasma concentrations occurring within 1 hour. Bioavailability is approximately 70% and not significantly affected by food. Distribution: Volume of distribution is 0.4 L/kg. Plasma protein binding is 93%, primarily to albumin. Metabolism: Minimally metabolized by hepatic cytochrome P450 enzymes (primarily CYP3A4). The majority (70-85%) is excreted unchanged. Elimination: Half-life is approximately 8.3 hours. Excreted primarily in urine (70%) and feces (10%) with 60% excreted within 24 hours.Contraindications
- Hypersensitivity to cetirizine, hydroxyzine, or any component of the formulation
- End-stage renal disease (CrCl <10 mL/min) unless undergoing dialysis
- History of severe hypersensitivity reactions to any piperazine derivatives
Warnings and Precautions
- Renal impairment: Dose adjustment required for moderate to severe impairment
- Sedation: Although less sedating than first-generation agents, somnolence may occur
- Urinary retention: Use with caution in patients with prostatic hyperplasia
- Pregnancy: Category B - use only if clearly needed
- Lactation: Excreted in breast milk; consider alternative feeding options
- Children <2 years: Safety and efficacy not established
Drug Interactions
- CNS depressants: Enhanced sedative effects with alcohol, benzodiazepines, opioids
- Theophylline: May slightly decrease cetirizine clearance (clinically insignificant)
- Ritonavir: May increase cetirizine concentrations (monitor for increased sedation)
- Anticholinergic agents: Potential additive effects
Adverse Effects
Common (≥1%):- Somnolence (14%)
- Fatigue (6%)
- Dry mouth (5%)
- Pharyngitis (2%)
- Dizziness (2%)
- Headache
- Nausea
- Abdominal pain
- Diarrhea
- Epistaxis
- Hypersensitivity reactions (angioedema, bronchospasm)
- Seizures
- Hepatitis
- Tachycardia
- Thrombocytopenia
Monitoring Parameters
- Therapeutic response and symptom control
- Signs of excessive sedation or cognitive impairment
- Renal function in patients with pre-existing renal disease
- Adverse effects, particularly in elderly patients
- Signs of hypersensitivity reactions
Patient Education
- Take medication as directed, typically once daily in the evening if sedation occurs
- Avoid alcohol and other CNS depressants while taking cetirizine
- Report severe drowsiness, difficulty urinating, or palpitations to healthcare provider
- Use caution when operating machinery or driving until response is known
- Store at room temperature away from moisture
- Do not crush or chew extended-release formulations
- Seek immediate medical attention for signs of allergic reaction (hives, difficulty breathing, swelling)
References
1. Simons FER. Advances in H1-antihistamines. N Engl J Med. 2004;351(21):2203-2217. 2. Cetirizine prescribing information. FDA Orange Book. Accessed January 2023. 3. Church MK, Maurer M, Simons FER, et al. Risk of first-generation H1-antihistamines: a GA²LEN position paper. Allergy. 2010;65(4):459-466. 4. Zuberbier T, Aberer W, Asero R, et al. The EAACI/GA²LEN/EDF/WAO guideline for the definition, classification, diagnosis and management of urticaria. Allergy. 2018;73(7):1393-1414. 5. Day JH, Briscoe MP, Rafeiro E, et al. Comparative clinical efficacy of cetirizine and fexofenadine for seasonal allergic rhinitis. Allergy Asthma Proc. 2006;27(5):386-393. 6. Golightly LK, Greos LS. Second-generation antihistamines: actions and efficacy in the management of allergic disorders. Drugs. 2005;65(3):341-384.