Cetirizine Hydrochloride 5mg/5ml Solution – Summary of Product Characteristics (SmPC) for healthcare professionals

1 NAME OF THE MEDICINAL PRODUCT

Cetirizine Hydrochloride 5mg/5ml Solution

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each ml of solution contains 1 mg cetirizine hydrochloride.

Excipient(s) with known effect:

• one ml of solution contains 2mg methyl parahydroxybenzoate
• one ml of solution contains 0.20mg propyl parahydroxybenzoate
• one ml of solution contains 500mg sorbitol
• one ml of solution contains 100mg glycerol
• one ml of solution contains 0.32mg sodium

For the full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Oral Solution

Clear, colourless solution

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

Adults and adolescents over 12 years of age:

Symptomatic treatment of allergic rhinitis (seasonal and perennial) associated allergic conjunctivitis, and chronic idiopathic urticaria.

Children 6-12 years:

Symptomatic treatment of allergic rhinitis (seasonal and perennial), and chronic idiopathic urticaria.

4.2 Posology and method of administration

Posology

Adults and adolescents over 12 years of age: 10ml

once daily Paediatric Population

Children aged between 6 and 11 years: Either 5ml twice daily or 10ml once a day. Children aged between 2 and 5 years: Either 2.5ml twice daily or 5ml once a day. Not recommended for children under 2 years of age.

Elderly subjects: data does 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 excreted 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. To use this dosing table, anestimate 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

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 his 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 Renal impairment above).

Method of administration

For oral use.

4.3 Contraindications

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

This medicinal product contains sorbitol, sodium, glycerol, methyl and propyl parahydroxy benzoates.

Patients with rare hereditary fructose intolerance (HFI), should not take cetirizine 5mg/5ml oral solution.

This medicine contains less than 1 mmol sodium (23 mg) per 10ml, that is to say essentially ‘sodium-free’.

Glycerol can be harmful in high doses. May cause headache, stomach upset and diarrhoea.

Sorbitol may cause gastrointestinal discomfort and mild laxative effect.

Methyl parahydroxybennzoate and Propyl parahydroxybenzoate may cause allergic reactions (possibly delayed)

At impaired function and renal functions, the elimination of cetirizine may be impaired. Caution should be exercised when administering cetirizine to these patients (see section 4.2 Posology, section 4.3 Contraindications).

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

In some patients, long-term treatment with cetirizine may lead to an increased risk of caries due to mouth dryness. The patients should therefore be informed about the importance of oral hygiene.

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 these symptoms were not present before. In some cases, symptoms may be intense and may require restarting the treatment, to which symptoms should resolve.

Paediatric Population

Use of this product is not recommended in children aged less than 2 years due to the amount of some excipients in the formulation

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, 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 / foetal development, parturition or postnatal development (see 5.3). Caution should 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 shows 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

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 hydrochloride.

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 events were reported for cetirizine 10 mg in the placebo-controlled 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 Populations

Adverse drug 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 effects reported during clinical studies and listed above, isolated cases of the following adverse drug reactions 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, <1/10); uncommon (≥1/1,000, <1/100); rare (≥1/10,000, <1/1,000); very rare (<1/10,000); not known (cannot be estimated from the available data):

Blood and lymphatic system disorders:

Very rare: thrombocytopenia

Immune system disorders:

Rare: hypersensitivity reactions (including 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, nightmares

Nervous system disorders:

Uncommon: paraesthesia.

Rare: convulsions, movement disorders

Very rare: dysgeusia, dyskinesia,

dystonia, syncope, tremor

Not Known: amnesia, memory

impairment

Eye disorders:

Rare: abnormal involuntary eye movements

Very rare: oculogyric crisis

Unknown: Accommodation disorder, blurred vision, mydriasis, eye pain, visual impairment, photophobia

Ear and labyrinth disorders:

Not known: vertigo

Cardiac disorders:

Rare: tachycardia

Gastrointestinal disorders:

Uncommon: diarrhoea

Hepatobiliary disorders

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

Not known: hepatitis

Skin and subcutaneous tissue disorders:

Uncommon:

rash,

pruritus

Rare:

urticaria

Very rare: angioedema, erythema multiforme, fixed drug eruption, angioneurotic oedema

Not known: acute generalised exanthematous pustulosis

Renal and urinary disorders:

Very rare: dysuria, enuresis, micturition difficulties Not known: urinary retention

Musculoskeletal and connective tissue disorders: Not known: arthralgia, myalgia

General disorders and administration site conditions: Uncommon:

asthenia,

malaise

Rare:

oedema

Reproductive

system and

breast

disorders:

Unknown:

Erectile

dysfunction

Respiratory, thoracic and mediastinal disorders: Unknown: Dyspnoea

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 the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search MHRA Yellow Card on Google Play and Apple App store.

4.9 Overdose

Toxicity: There is 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 to 500 mg to an adult gave no symptoms at all.

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 intake of at least five 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. The patient should be kept under clinical observation for at least four hours after ingestion, and the blood pressure, heart rate and vital signs monitored until stable. In symptomatic cases, ECG should be performed.

Oral activated charcoal (50 g for an adult, 10-15 g for a child) should be considered if more than 2.5 mg/kg cetirizine has been ingested within one hour,

Cetirizine is not effectively removed by haemodialysis

5.1 Pharmacodynamic properties

ATC Code: R06A E07

Pharmacotherapeutic group: Antihistamine for systemic use, piperazine derivative

Mechanism of action

Cetirizine, a human metabolite of hydroxyzine, is a potent and selective antagonist of eriheral H1-receptors. In vitro receptor binding studies have shown no measurable affinity for receptors other than H1-receptors.

Pharmacodynamic effects

In addition to its anti-H1 effect, cetirizine was shown to display anti-allergic activities: at a dose of 10mg once or twice daily, it inhibits the late phase recruitment of eosinophils, in the skin and conjunctiva of atopic subjects submitted to allergen challenge.

Clinical efficacy and safety

Studies in healthy volunteers show that cetirizine, at doses of 5 and 10mg strongly inhibits the wheal and glare reactions induced by very high concentrations of histamine into the skin, but the correlation with efficacy is not established.

In a six-week, placebo-controlled study of 186 patients with allergic rhinitis and concomitant mild to moderate asthma, cetirizine 10mg once daily improved rhinitis symptoms and did not later pulmonary function. This study supports the safety of administering cetirizine to allergic patients with mild to moderate asthma.

In a placebo-controlled study, cetirizine given at the high daily dose of 60mg for seven days did not cause statistically significant prolongation of QT interval.

At the recommended dosage, cetirizine has demonstrated that it improves the quality of life of patients with perennial and seasonal allergic rhinitis.

Paediatric population

In a 35-day study in children aged 5 to 12, no tolerance to the antihistamine effect (suppression of wheal and flare) of cetirizine was found. When a treatment with cetirizine is stopped after repeated administration, the skin recovers its normal reactivity to histamine within 3 days.

5.2 Pharmacokinetic properties

Absorption

The steady-state peak plasma concentration is approximately 300 ng/ml and is achieved within 1.0 +/- 0.5 h. The distribution of pharmacokinetic parameters such as peak plasma concentration (C_max) and area under curve (AUC) is unimodal.

The extent of absorption of cetirizine is not reduced with food, although the rate of absorption is decreased. The extent of bioavailability is similar when cetirizine is given as solutions, capsules or tablets.

Distribution

The apparent volume of distribution is 0.50 l/kg. Plasma protein binding of cetirizine is 93 +/- 0.3%. Cetirizine does not modify the protein binding of warfarin.

Biotransformation

Cetirizine does not undergo extensive first pass metabolism.

Elimination

The terminal half-life is approximately 10 hours and no accumulation is observed for cetirizine following daily doses of 10 mg for 0 days. About two third of the dose are excreted unchanged in urine.

Linearity/ Non-linearity

Cetirizine exhibits linear kinetics over the range of 5 to 60mg.

Renal impairment: The pharmacokinetics of the drug was similar in patients with mild impairment (creatinine clearance higher than 40 ml/min) and healthy volunteers. Patients with moderate renal impairment had a 3-fold increase in half-life and 70% decrease in clearance compared to healthy volunteers.

Patients on haemodialysis (creatinine clearance less than 7 ml/min) given a single oral 10mg dose of cetirizine had a 3-fold increase in half-life and a 70% decrease in clearance compared to normal. Cetirizine was poorly cleared by haemodialysis Dosing adjustment is necessary in patients with moderate or severe renal impairment (see section 4.2).

Hepatic impairment: Patients with chronic liver diseases (hepatocellular, cholestatic, and biliary cirrhosis) given 10 or 20 mg of cetirizine as a single dose had a 50 % increase in half-life along with a 40 % decrease in clearance compared to healthy subjects.

Dosing adjustment is only necessary in patients with hepatic impairment if concomitant renal impairment is present.

Elderly: Following a single 10 mg oral dose, half-life increased by about 50 % and clearance decreased by 40 % in 16 elderly subjects compared to the normal subjects. The decrease in cetirizine clearance in these elderly volunteers appeared to be related to their decreased renal function.

Paediatric population: The half-life of cetirizine was about 6 hours in children of 6-12 years and 5 hours in children 2-6 years. In infants and toddlers aged 6 to 24 months, it is reduced to 3.1 hours.

5.3 Preclinical Safety Data

Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, toxicity to reproduction and development, genotoxicity or carcinogenicity.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Methyl parahydroxybenzoate (E218)

Propyl parahydroxybenzoate (E216)

Sorbitol solution (70%)

Glycerol

Sodium Citrate

Citric acid

Propylene glycol

Monoammonium Glycyrrhizinate

Purified water

Flavours

Pineapple Singapore flavour (flavouring agent and propylene glycol)

Sweet orange No. 1(flavouring agent and propylene glycol)

6.2 Incompatibilities

Not applicable

6.3 Shelf life

Unopened: 3 years

After opening: 6 months

6.4 Special precautions for storage

No special precautions for storage

6.5 Nature and contents of container

Pack size: 200ml bottle.

Packaging: Type III amber glass bottle with Tamper proof polypropylene closure.

6.6 Special precautions for disposal

No special requirements.

7 MARKETING AUTHORISATION HOLDER

Kent Pharmaceuticals Limited,

Westminster Industrial Estate,

Repton Road,

Measham,

DE12 7DT,

England.

8 MARKETING AUTHORISATION NUMBER(S)

PL 08215/0128

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE

AUTHORISATION

12/05/2005 / 22/02/2010

10 DATE OF REVISION OF THE TEXT

17/02/2026