Cetirizine

In sensitive patients, the concurrent use of alcohol or other CNS depressants may cause additional reductions in alertness and impairment of performance, although cetirizine does not potentiate the effect of alcohol (0.5 g/L blood levels).

There are no data to document the efficacy/safety ratio in patients with renal impairment. Since cetirizine is mainly excreted via renal route, in cases no alternative treatment can be used, the dosing intervals must be individualized according to renal function.

Refer to the following table and adjust the dose as indicated. To use this dosing table, an estimate of the patient’s creatinine clearance (CL_cr) in ml/min is needed. The CL_cr (ml/min) may be estimated from serum creatinine (mg/dl) determination using the following formula:

Cl_cr = [140 – age (years) x weight (kg)] / 72 x serum creatinine (mg/dl) (x 0.85 for women)

Dosing adjustments for adult patients with impaired renal function:

Caution is recommended in epileptic patients and patients at risk of convulsions.

Caution should be taken in patients with predisposition factors of urinary retention (e.g. spinal cord lesion, prostatic hyperplasia) as cetirizine may increase the risk of urinary retention.

For cetirizine prospectively collected data on pregnancy outcomes do not suggest potential for maternal or foetal/embryonic toxicity above background rates.

Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/fetal development, parturition or postnatal development. Caution should be exercised when prescribing to pregnant women.

Cetirizine is excreted in human milk at concentrations representing 25% to 90% of those measured in plasma, depending on sampling time after administration. Therefore, caution should be exercised when prescribing cetirizine to lactating women.

Fertility

Limited data is available on human fertility but no safety concern has been identified. Animal data show no safety concern for human reproduction.

Objective measurements of driving ability, sleep latency and assembly line performance have not demonstrated any clinically relevant effects at the recommended dose of 10 mg. However, patients who experience somnolence should refrain from driving, engaging in potentially hazardous activities or operating machinery. They should not exceed the recommended dose and should take their response to the medicinal product into account.

Clinical studies

Overview

Clinical studies have shown that cetirizine at the recommended dosage has minor undesirable effects on the CNS, including somnolence, fatigue, dizziness and headache. In some cases, paradoxical CNS stimulation has been reported.

Although cetirizine is a selective antagonist of peripheral H₁-receptors and is relatively free of anticholinergic activity, isolated cases of micturition difficulty, eye accommodation disorders and dry mouth have been reported.

Instances of abnormal hepatic function with elevated hepatic enzymes accompanied by elevated bilirubin have been reported. Mostly this resolves upon discontinuation of the treatment with cetirizine dihydrochloride.

Listing of ADRs

Double blind controlled clinical trials comparing cetirizine to placebo or other antihistamines at the recommended dosage (10 mg daily for cetirizine), of which quantified safety data are available, included more than 3200 subjects exposed to cetirizine.

From this pooling, the following adverse reactions were reported for cetirizine 10 mg in the placebocontrolled trials at rates of 1.0% or greater:

Although statistically more common than under placebo, somnolence was mild to moderate in the majority of cases.

Objective tests as demonstrated by other studies have demonstrated that usual daily activities are unaffected at the recommended daily dose in healthy young volunteers.

Paediatric population

Adverse reactions at rates of 1% or greater in children aged from 6 months to 12 years, included in placebo-controlled clinical trials are:

Post-marketing experience

In addition to the adverse reactions reported during clinical studies and listed above, the following undesirable effects have been reported in post-marketing experience. Undesirable effects are described according to MedDRA System Organ Class and by estimated frequency based on post-marketing experience.

Frequencies are defined as follows: Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000), not known (cannot be estimated from the available data)

Blood and lymphatic disorders

Very rare: thrombocytopenia

Immune system disorders

Rare: hypersensitivity

Very rare: anaphylactic shock

Metabolism and nutrition disorders

Not known: increased appetite

Psychiatric disorders

Uncommon: agitation

Rare: aggression, confusion, depression, hallucination, insomnia

Very rare: tics

Not known: suicidal ideation, nightmare

Nervous system disorders

Uncommon: paraesthesia

Rare: convulsions

Very rare: dysgeusia, syncope, tremor, dystonia, dyskinesia

Not known: amnesia, memory impairment

Eye disorders

Very rare: accommodation disorder, blurred vision, oculogyration

Ear and labyrinth disorders

Not known: vertigo

Cardiac disorders

Rare: tachycardia

Gastro-intestinal disorders

Uncommon: diarrhoea

Hepatobiliary disorders

Rare: hepatic function abnormal (increased transaminases, alkaline phosphatase, γ-GT and bilirubin)

Skin and subcutaneous tissue disorders

Uncommon: pruritus, rash

Rare: urticaria

Very rare: angioneurotic oedema, fixed drug eruption

Not known: acute generalized exanthematous pustulosis

Musculosk eletal and connective tissue disorders

Not known: arthralgia

Renal and urinary disorders

Very rare: dysuria, enuresis

Not known: urinary retention

General disorders and administration site conditions

Uncommon: asthenia, malaiseRare: oedema

Investigations

Rare: weight increased

Description of selected adverse reactions

After discontinuation of cetirizine, pruritus (intense itching) and/or urticaria have been reported.