4.1. Therapeutic indications

Cetirizine dihydrochloride 1 mg/ml oral solution is indicated in adults and children aged 2 years and above:

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

- for the relief of symptoms of chronic idiopathic urticaria.

4.2. Posology and method of administration

Posology

10 mg once daily (10 ml oral solution (2 full spoons)).

Special population

Elderly

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

Renal impairment

There are no data to document the efficacy/safety ratio in patients with renal impairment. Since cetirizine is mainly eliminated via renal route (see section 5.2), 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.

Dosing adjustments for adult patients with impaired renal function

Group

Estimated Glomerular Filtration Rate (eGFR) (ml/min)

Dosage and frequency

Normal renal function

≥90

10 mg once daily

Mildly decreased renal function

60 - < 90

10 mg once daily

Moderately decreased renal function

30 – < 60

5 mg once daily

Severely decreased renal function

15 - <30 not requiring dialysis

5 mg once every 2 days

End-stage renal disease

<15 requiring dialysis treatment

Contraindicated

Hepatic impairment

No dose adjustment is needed in patients with solely hepatic impairment. In patients with hepatic impairment and renal impairment, adjustment of the dose is recommended (see Renal impairment above).

Paediatric population

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

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

Adolescents over 12 years of age: 10 mg once daily (10 ml oral solution (2 full spoons)).

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

Method of administration:

The solution can be swallowed as such.

4.3. Contraindications

Hypersensitivity to the active substance, to any of the excipients listed in section 6.1, to hydroxyzine or to any piperazine derivatives.

Patients with end-stage renal disease with an eGFR (estimated Glomerular Filtration Rate) below 15 ml/min.

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.

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

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

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

Excipients

This medicinal product contains 1575 mg sorbitol (E 420) in each 5 ml which is equivalent to 315 mg/ml. Patients with hereditary fructose intolerance (HFI) should not take / be given this medicinal product. Sorbitol may cause gastrointestinal discomfort and mild laxative effect.

This medicinal product contains methylparahydroxybenzoate (E 218) and propylparahydroxybenzoate (E 216) which may cause allergic reactions (possibly delayed).

This medicinal product contains 250 mg propylene glycol (E 1520) in each 5 ml which is equivalent to 50 mg/ml.

This medicinal product contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially 'sodium-free'.

Paediatric population

Due to the amount of some excipients in the formulation, the use of the product is not recommended in children aged less than 2 years.

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

Due to the 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.

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).

4.6. Fertility, pregnancy and lactation

Pregnancy

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 nevertheless be exercised when prescribing to pregnant women.

Breast-feeding

Cetirizine passes into breast milk. A risk of side effects in breastfed infants cannot be excluded. 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.

4.7. Effects on ability to drive and use machines

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.

4.8. Undesirable effects

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 placebo-controlled trials at rates of 1.0 % or greater:

Adverse reactions

(WHO-ART)

Cetirizine 10 mg

(n= 3260)

Placebo

(n = 3061)

General disorders and administration site conditionsFatigue

1.63 %

0.95 %

Nervous system disordersDizzinessHeadache

1.10 %

7.42 %

0.98 %

8.07 %

Gastro-intestinal disordersAbdominal painDry mouthNausea

0.98 %

2.09 %

1.07 %

1.08 %

0.82 %

1.14 %

Psychiatric disordersSomnolence

9.63 %

5.00 %

Respiratory, thoracic and mediastinal disordersPharyngitis

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.

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:

Adverse reactions

(WHO-ART)

Cetirizine

(n=1656)

Placebo

(n =1294)

Gastro-intestinal disordersDiarrhoea

1.0 %

0.6 %

Psychiatric disordersSomnolence

1.8 %

1. 4 %

Respiratory, thoracic and mediastinal disordersRhinitis

1.4 %

1.1 %

General disorders and administration site conditionsFatigue

1.0 %

0.3 %

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, oculogyric crisis

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)

Not known: hepatitis

Skin and subcutaneous tissue disorders

Uncommon: pruritus, rash

Rare: urticaria

Very rare: angioneurotic oedema, fixed drug eruption

Not known: acute generalized exanthematous pustulosis

Musculoskeletal and connective tissue disorders

Not known: arthralgia, myalgia

Renal and urinary disorders

Very rare: dysuria, enuresis

Not known: urinary retention

General disorders and administration site conditions

Uncommon: asthenia, malaise

Rare: oedema

Investigations

Rare: weight increased

Description of selected adverse reactions

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

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:

Yellow Card Scheme

Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9. Overdose

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.

Management

There is no known specific antidote to cetirizine.

Should overdose occur, symptomatic or supportive treatment is recommended. Gastric lavage may be considered shortly after ingestion of the drug.

Cetirizine is not effectively removed by haemodialysis.