Cetirizine
Second-Generation Antihistamine for Allergic Conditions
Cetirizine is a second-generation antihistamine and one of the most widely prescribed active substances for allergic conditions worldwide. The compound was developed from the antihistamine hydroxyzine and differs from first-generation antihistamines by a markedly reduced sedating effect. In many countries cetirizine is available without a prescription as tablets, film-coated tablets, drops and syrup, and forms part of the standard therapy for hay fever, chronic urticaria and other allergic reactions.
Well-known brand names include Zyrtec and Reactine, alongside numerous generics. The active substance has been approved since the late 1980s and is thoroughly studied. Since the introduction of the active enantiomer levocetirizine, an even more selective variant is available that achieves comparable effects at half the dose.
Mechanism of Action
Cetirizine acts as a selective, peripheral histamine H1-receptor antagonist. The compound competitively blocks H1-receptors on smooth muscle, blood vessels, the bronchial mucosa and other tissues, thereby preventing histamine from exerting its typical effects: increased vascular permeability, pruritus, bronchoconstriction and erythema formation are all inhibited.
Unlike first-generation antihistamines, cetirizine crosses the blood-brain barrier only to a limited extent because it exists as a zwitterion at physiological pH and is a substrate of P-glycoprotein. As a result, central nervous system effects are substantially reduced compared with older antihistamines, though not completely absent.
In addition, cetirizine exerts anti-allergic effects that go beyond mere H1 blockade. It inhibits the migration of eosinophils into allergically reacting tissue, reduces the release of inflammatory mediators from mast cells and influences the expression of adhesion molecules. These mechanisms contribute to dampening the late-phase allergic response.
Indications
- Allergic rhinitis: Seasonal (hay fever) and perennial rhinitis caused by house dust, animal dander or other allergens
- Allergic conjunctivitis: Pruritus, redness and lacrimation of the eyes during allergic reactions
- Chronic spontaneous urticaria: Long-term management of persistent hives
- Acute urticaria: Short-term relief of wheals and pruritus
- Atopic dermatitis: Symptomatic relief of pruritus as part of adjunctive treatment
- Insect-sting reactions: Local allergic skin reactions following stings
- Contact allergy: Symptomatic treatment of mild to moderate reactions
Dosage and Administration
For adults and children aged 12 years and over, the usual daily dose is 10 mg cetirizine, taken either as a single dose in the evening or as two divided doses of 5 mg in the morning and evening. The dose may be taken independently of meals. In patients with impaired renal function (creatinine clearance below 50 ml/min), a dose reduction to 5 mg daily or 10 mg every two days is indicated. Children aged 2 to 6 years generally receive 2.5 mg twice daily as drops or syrup; children aged 6 to 12 years receive 5 mg twice daily or 10 mg once daily.
No routine dose adjustment is required in hepatic insufficiency because cetirizine is predominantly renally eliminated. Concomitant renal function should nevertheless be considered. Long-term treatment should be regularly reviewed by a physician, particularly in chronic urticaria.
Side Effects
Cetirizine is generally well tolerated. The most common undesirable effect (more than 1 in 10 users) is drowsiness, which can still occur despite the improved selectivity of second-generation compounds, especially at higher doses or in individuals with particular sensitivity. Dry mouth, headache and fatigue occur in more than 1 in 100 patients.
Rare side effects include gastrointestinal complaints such as nausea and abdominal pain. Isolated cases of cardiac arrhythmias, hepatic dysfunction and extrapyramidal symptoms have been reported, although these are very rare. Allergic reactions to cetirizine itself are possible but unusual.
Because cetirizine may impair reaction time, individual tolerability should be assessed before driving vehicles or operating machinery. Alcohol can potentiate the sedating effect.
Drug Interactions
Clinically relevant pharmacokinetic interactions are uncommon with cetirizine because the compound is metabolised only minimally via the cytochrome P450 system. Concomitant use of other centrally depressant substances such as benzodiazepines, opiates or alcohol can additively enhance sedation. MAO inhibitors should not be used simultaneously.
Theophylline at high doses may marginally reduce the clearance of cetirizine. Concomitant use with other antihistamines is not recommended. In patients with epilepsy, the seizure threshold may be affected.
Special Notes
During pregnancy, cetirizine should be used only after careful consideration. Animal studies show no teratogenic effects; however, controlled studies in humans during the first trimester are lacking. In the third trimester, use may lead to withdrawal symptoms or respiratory depression in the neonate. Cetirizine passes into breast milk and should therefore be avoided during lactation or used only after medical consideration.
In children under 2 years, cetirizine should be used only on medical prescription. Patients with galactose intolerance or glucose-galactose malabsorption should avoid lactose-containing tablet formulations. Renal function in elderly patients requires special attention when determining the dose.
Frequently Asked Questions
How quickly does cetirizine take effect?
Cetirizine is rapidly absorbed from the gastrointestinal tract. Maximum plasma concentration is reached after approximately one hour. The effect often begins within 20 to 60 minutes and, owing to the long half-life of 7 to 10 hours, persists throughout the day.
Can cetirizine be taken long-term?
In chronic urticaria, long-term use under medical supervision is possible and is provided for in clinical guidelines. In seasonal rhinitis, cetirizine is used only during the pollen season. Self-managed long-term therapy without medical oversight is not advisable.
Does cetirizine cause dependence?
Cetirizine has no dependence potential. After discontinuation, symptoms may occasionally recur temporarily; this is attributable to the return of the underlying condition rather than to a withdrawal syndrome.
Can cetirizine be combined with alcohol?
Concomitant use of cetirizine and alcohol can enhance the sedating effect. It is recommended to avoid alcohol during treatment or at least to reduce consumption substantially.
References and Further Information
- Summary of Product Characteristics for Cetirizine (current approved version, various manufacturers)
- S2k Guideline on Urticaria of the German Dermatological Society (DDG)
- ARIA Guideline (Allergic Rhinitis and its Impact on Asthma)
- European Medicines Agency (EMA): Assessment Report Cetirizine
- Federal Institute for Drugs and Medical Devices (BfArM)