4.1. Therapeutic indications

In adults and children 2 years and above:

- Cetirizine is indicated for the relief of nasal and ocular symptoms of seasonal and perennial allergic rhinitis.

- Cetirizine is indicated for the relief of chronic idiopathic urticaria.

4.2. Posology and method of administration

Children aged from 2 to 6 years: 2.5mg twice daily (2.5 ml of oral solution twice daily).

Children aged from 6 to 12 years: 5 mg twice daily (5 ml of oral solution twice daily).

Adults and adolescents over 12 years of age: 10 mg once daily (10 ml of oral solution once daily).

Elderly subjects: data do not suggest that the dose needs to be reduced in elderly subjects provided that the renal function is normal.

Patients with moderate to severe renal impairment: there are no data to document the efficacy/safety ratio in patients with renal impairment. Since cetirizine is mainly excreted via renal route (see section 5.2), in cases no alternative treatment can be used, the dosing intervals must be individualised 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 (CLcr) in ml/min is needed. The CLcr (ml/min) may be estimated from serum creatinine (mg/dl) determination using the following formula:

Dosing Adjustments for Adult Patients with Impaired Renal Function

Group

Creatinine clearance

(ml/min)

Dosage and frequency

Normal

≥ 80

10 mg once daily

Mild

50-79

10 mg once daily

Moderate

30-49

5 mg once daily

Severe

< 30

5 mg once every 2 days

End-stage renal disease - Patients undergoing dialysis

< 10

Contra-indicated

In paediatric patients suffering from renal impairment, the dose will have to be adjusted on an individual basis taking into account the renal clearance of the patient, their age and body weight.

Patients with hepatic impairment: no dose adjustment is needed in patients with solely hepatic impairment.

Patients with hepatic impairment and renal impairment: dose adjustment is recommended ( see Patients with moderate to severe renal impairment above).

4.3. Contraindications

Hypersensitivity to the active substance, to any of the excipients, to hydroxyzine or to any piperazine derivatives.

Patients with severe renal impairment at less than 10 ml/min creatinine clearance.

4.4. Special warnings and precautions for use

At therapeutic doses, no clinically significant interactions have been demonstrated with alcohol (for a blood alcohol level of 0.5 g/L). Nevertheless, precaution is recommended if alcohol is taken concomitantly.

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 (see Section Adverse Reactions).

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

The use of the product is not recommended in children aged less than 2 years.

Methyl parahydroxybenzoate and propyl parahydroxybenzoate may cause allergic reactions (possibly delayed).

This product contains Sorbitol. Patients with rare hereditary problems of fructose intolerance, should not take cetirizine 1 mg/ml oral solution.

Pruritus and/or urticaria may occur when cetirizine is stopped, even if those symptoms were not present before treatment initiation (see Section Adverse Reactions). In some cases, the symptoms may be intense and may require treatment to be restarted. The symptoms should resolve when the treatment is restarted.

Allergy skin tests are inhibited by antihistamines and a wash-out period (of 3 days) is required before performing them.

4.5. Interaction with other medicinal products and other forms of interaction

Due to pharmacokinetic, pharmacodynamic and tolerance profile of cetirizine, no interactions are expected with this antihistamine. Actually, neither pharmacodynamic nor significant pharmacokinetic interaction was reported in drug-drug interactions studies performed, notably with pseudoephedrine or theophylline (400 mg/day).

The extent of absorption of cetirizine is not reduced with food, although the rate of absorption is decreased.

Alcohol and other CNS depressants

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 (see Section Warnings and Precautions).

4.6. Pregnancy and lactation

Data on a limited number of exposed pregnancies indicate no adverse effects of cetirizine on pregnancy or on health of foetus/new born child. To date no other relevant epidemiological data are available.

Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or post natal development (see 5.3). Caution should be exercised when prescribing to pregnant women.

Breast feeding

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

4.7. Effects on ability to drive and use machines

Cetirizine may have minor or moderate influence on the patient's ability to react. This should be considered when extra alertness is required e.g. when driving. Cetirizine may potentiate the effects of alcohol and CNS depressants.

In sensitive patients, concurrent use with alcohol or other CNS depressants may cause additional reductions in alertness and impairment of performance.

4.8. Undesirable effects

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 hydrochloride.

Clinical trials

Double blind controlled clinical or pharmacoclinical 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 events were reported for cetirizine 10 mg in the placebo-controlled trials at rates of 1.0% or greater:

Adverse event

(WHO-ART)

Cetirizine 10 mg

(n=3260)

Placebo

(n=3061)

General disorders and administration site conditions

Fatigue

1.63%

0.95%

Nervous system disorders

Dizziness

Headache

1.10%

7.42%

0.98%

8.07%

Gastro-intestinal system disorders

Abdominal pain

Dry mouth

Nausea

0.98%

2.09%

1.07%

1.08%

0.82%

1.14%

Psychiatric disorders

Somnolence

9.63%

5.00%

Respiratory, thoracic and mediastinal disorders

Pharyngitis

1.29%

1.34%

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.

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

Adverse event

(WHO-ART)

Cetirizine 10 mg

(n=1656)

Placebo

(n=1294)

Gastro-intestinal system disorders

Diarrhoea

1.0%

0.6%

Psychiatric disorders

Somnolence

1.8%

1.4%

Respiratory, thoracic and mediastinal disorders

Rhinitis

1.4%

1.1%

General disorders and administration site conditions

Fatigue

1.0%

0.3%

The adverse effects listed below are classified by system organ class and frequency according to the following convention: 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) or very rare (<1/10,000).

MEDRA SOC

Adverse reaction

Frequency

Blood and lymphatic disorders

Thrombocytopenia

Very rare

Metabolism and nutrition disorders:

Increased appetite

Not known

Psychiatric disorders:

Agitation

Uncommon:

Aggression, confusion, depression, hallucinations, insomnia

Rare

Tic

Very rare:

Suicidal ideation, nightmare

Not known:

Nervous system disorders:

Paraesthesia

Uncommon

Convulsions, movement disorders

Rare

Dysgeusia, syncope, tremor, dystonia, dyskinesia

Very rare

Amnesia, memory impairment

Unknown

Eye disorders

Accommodation disorder, blurred vision, oculogyration

Very rare

Ear and labyrinth disorders

Vertigo

Not known

Cardiac disorders

Tachycardia

Rare

Gastro-intestinal disorders

Diarrhoea

Uncommon

Hepatobiliary disorders:

Hepatic function abnormal (increased transaminases, alkaline phosphates, γ-GT and bilirubin)

Rare

Hepatitis

Unknown

Skin and subcutaneous tissue disorders

Pruritus, rash

Uncommon

Urticaria

Rare

Angioneurotic oedema, fixed drug eruption

Very rare

Acute generalized exanthematous pustulosis (AGEP)

Unknown

Musculoskeletal and connective tissue disorder

Arthralgia

Not known

Renal and urinary disorders

Dysuria, enuresis

Very rare

Urinary retention (see section Warnings and Precautions)

Not known

General disorders and administration site conditions

Asthenia, malaise

Uncommon:

Oedema

Rare

Investigations

Weight increased

Rare

Immune system disorders

Hypersensitivity

Rare

Anaphylactic shock

Very rare

Skin reactions occuring after discontinuation of cetirizine

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

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at:www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9. Overdose

Toxicity: Limited experience of overdosing. 20 mg to a 2 year old, 30 mg to a 3 year old and 40 mg to an 11 year old did not give any symptoms. 60 mg to a 4 year old gave mild intoxication, 400 mg to a 14 year old gave mild symptoms while 400-500 mg to an adult gave no symptoms at all.

a) Symptoms

Symptoms observed after an overdose of cetirizine are mainly associated with CNS effects or with effects that could suggest an anticholinergic effect. Adverse events reported after an intake of at least 5 times the recommended daily dose are: confusion, diarrhoea, dizziness, fatigue, headache, malaise, mydriasis, pruritus, restlessness, sedation, somnolence, stupor, tachycardia, tremor, and urinary retention.

b) Management

There is no known specific antidote to cetirizine.

Should overdose occur, symptomatic or supportive treatment is recommended. Cetirizine is not effectively removed by dialysis.