SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Care Hayfever and Allergy 1mg/mL Solution

2.    QUALITATIVE AND QUANTITATIVE COMPOSITION

Each 1 ml of solution contains 1mg of cetirizine hydrochloride.

For excipients, see 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.

Children 2-6 years

Symptomatic treatment of seasonal allergic rhinitis

4.2    Posology and method of administration

Adults and adolescents over 12 years of age: 2 x 5 ml once daily.

If drowsiness occurs, the solution can be administered in the evening.

Children 6-12 years:

2 x 5ml once daily or 5ml taken twice daily (morning and evening).

Children 2-6years or weighing less than 30Kg:

5ml taken once daily or 2.5ml twice daily.

At present there is insufficient clinical data to recommend the use of cetirizine in children under 2 years of age.

Patients with moderate to severe renal impairment: 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 (CLcr) in ml/min is needed. The CL_cr (ml/min) may be estimated from serum creatinine (mg/dl) determination using the following formula:

[ 140 - age(years) ] x weight (kg)

CL_cr =    - ( x 0.85 for

72 x serum creatinine (mg/dl)

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 pediatric 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 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: adjustment of the dose is recommended (see Patients with renal impairment above).

There is no evidence that the dose needs to be modified for healthy elderly patients provided that the renal function is normal. The duration of the treatment may vary depending on the symptoms.

4.3 Contraindications

Hypersensitivity to any component of the preparation, to hydroxyzine or to piperazine derivatives.

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

Contains sorbitol. Patients with rare hereditary problems of fructose intolerance should not take cetirizine 1 mg/ml oral solution.

4.4    Special warnings and precautions for use

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

In cases of impaired hepatic function and renal function, the elimination of cetirizine may be impaired. Caution should be exercised when administering cetirizine to these patients. (see section 4.2 posology and 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), however cetirizine may potentiate the effects of alcohol. Therefore caution is recommended during concomitant use of alcohol.

Caution is recommended with concomitant use of CNS depressants.

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

Methyl parahydroxybenzoate and propyl parahydroxybenzoate included in the 1 mg/ml oral solution may cause allergic reactions (possibly delayed).

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

4.5    Interaction with other medicinal products and other forms of interaction

Allergy testing: Allergy skin tests are inhibited by antihistamines and a washout period is required before performing them. Use of cetirizine must be discontinued three days before allergy tests. Cetirizine may potentiate the effects of alcohol. Therefore caution is recommended during concomitant use of alcohol. Caution is recommended during concomitant use of CNS depressants.

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.

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.

Lactation

Cetirizine is excreted in human milk at concentrations representing 0.25 to 0.90 those measured in plasma, depending on sampling time after administration. Therefore, caution should be exercised when prescribing cetirizine to lactating women.

4.7    Effects on ability to drive and use machines

Cetirizine may have minor or moderate influence on the patient’s ability to react. 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. This should be considered when extra alertness is required e.g. patients intending to drive, engaging in potentially hazardous activities or operating machinery should not exceed the recommended dose and should take their response to the medicinal product into account.

In sensitive patients cetirizine may potentiate the effects of alcohol and CNS depressants, if used concurrently there may be additional reductions in alertness and impairment of performance.

4.8    Undesirable effects

Clinical studies have shown that cetirizine at the recommended dosage has minor adverse effects on the CNS, including somnolence in children and adults, fatigue, dizziness and headache. In some cases, paradoxical CNS stimulation has been reported; mouth dryness, drowsiness, agitation, abdominal complaints and digestive disorders. Exceptionally, cases of allergic reactions such as cutaneous reactions and angioedema (Quincke’s Oedema) have been reported.

Although cetirizine is a selective antagonist of peripheral Hl-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 drug.

a) Clinical trials

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	Cetirizine 10	Placebo
(WHO-ART)	mg (n= 3260)	(n = 3061)
Body as a whole - general disorders Fatigue	1.63 %	0.95 %
Central and peripheral nervous system disorders Dizziness	1.10 %	0.98 %
Headache	7.42 %	8.07 %
Gastro-intestinal system disorders Abdominal pain	0.98 %	1.08 %
Dry mouth	2.09 %	0.82 %
Nausea	1.07 %	1.14 %
Psychiatric disorders Somnolence	9.63 %	5.00 %
Respiratory system 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 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 system disorders Diarrhoea	1.0 %	0.6 %
Psychiatric disorders Somnolence	1.8 %	1. 4 %
Respiratory system disorders Rhinitis	1.4 %	1.1 %
Body as a whole - general disorders Fatigue	1.0 %	0.3 %

b) 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

• Psychiatric disorders:

Uncommon: agitation

Rare: aggression, confusion, depression, hallucination,

insomnia

Very rare: tics

• Nervous system disorders:

Uncommon: paraesthesia Rare: convulsions

Very rare: dysgeusia, dyskinesia, dystonia, syncope, tremor Not known: amnesia, memory impairment

• Eye disorders:

Very rare: accommodation disorder, blurred vision, oculogyration

• Cardiac disorders:

Rare: tachycardia

• Gastro-intestinal disorders:

Uncommon: diarrhoea

• Hepatobiliary disorders:

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

• Skin and subcutaneous tissue disorders: Uncommon: pruritus, rash

Rare: urticaria

Very rare: angioneurotic oedema, fixed drug eruption

• Renal and urinary disorders:

Very rare: dysuria, enuresis

• General disorders and administration site conditions: Uncommon: asthenia, malaise Rare: oedema

• Investigations:

Rare: weight increased

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.

4.9 Overdose

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

Symptoms of overdosage reported with antihistamine substances e.g. cetirizine, are mainly associated with CNS effects that could suggest an anticholinergic effect. Adverse events reported after an intake of a least 5 times the recommended daily dose are:

Confusion, diarrhoea, dizziness, fatigue, malaise, pruritis, restlessness, stupor, somnolence; unconsciousness and/or excitation (principally in children), ataxia, tremor, headache, hallucinations, seizures, dry mouth, flush, hyperthermia, mydriasis, urine retention, tachycardia and in the case of massive doses, possible fall in blood pressure and arrhythmias. Nausea and vomiting. Also extrapyramidal symptoms are possible. Cetirizine has a low sedative and anticholinergic effect. Sedation can be a symptom of overdose, it can occur after a single dose of less than 50mg.

Treatment: At the present time there is no specific antidote. Experience of overdosing is limited and no severe intoxication has been reported to date. Primary treatment should be gastric lavage, if justified and charcoal. Symptomatic or supportive treatment should be considered in the case of acute intoxication, following ingestion of short occurrence, such as diazepam for seizures or acute dystonias. Cetirizine is not effectively removed by dialysis.

5. PHARMACOLOGICAL PROPERTIES

5.1.    Pharmacodynamic properties

ATC code: R06AE07

Pharmacotherapeutic group: Antihistamines for systemic use Cetirizine hydrochloride is a racemate and an anti-allergic with specific histamine H₁-receptor blocking characteristics.

Cetirizine inhibits cutaneous reactions in allergic individuals through VIP (Vasoactive Intestinal Polypeptide) and substance P, neuropeptides that are considered to be involved in the allergic reaction. Effect is reached within 2 hours with a maximum effect after 4 hours, and remains for at least 24 hours. In allergic individuals, cetirizine inhibits the recruitment of eosinophils after stimulation with allergens and non selective histamine liberators, by a mechanism that is not primarily explained by the H₁-receptor blocking characteristics of the pharmaceutical.

5.2.    Pharmacokinetic properties

Cetirizine is absorbed with small inter-individual variations. Cetirizine has not been given intravenously, therefore the bioavailability, clearance and volume of distribution (Vd) are unknown. Maximum plasma concentration is achieved within 1 hour and the terminal half-life is about 10 hours in adults and 6 hours in children between the age of 6-12 years. The grade of protein binding in plasma is about 93%. Cetirizine is metabolised to a small extent with a known inactive main metabolite. 60% of a dose of cetirizine is eliminated in unchanged form via the kidneys within 96 hours. Repeated administration does not lead to any accumulation, nor is the absorption or elimination affected. In cases of impaired kidney function, the elimination is slower and the half-life is prolonged. Elimination will also be decreased in cases of hepatic impairment.

There is no evidence that the pharmacokinetics of cetirizine is altered in elderly patients unless renal or hepatic function is reduced.

5.3.    Preclinical safety data

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

6    PHARMACEUTICAL PARTICULARS

6.1    List of excipients

Glycerol Propylene glycol Sorbitol Methylparaben Propylparaben Sodium acetate Acetic acid Saccharin sodium Banana flavour Purified water

6.2. Incompatibilities

Not applicable.

6.3.    Shelf life

3 years.

6.4.    Special precautions for storage

No special precautions for storage.

6.5    Nature and contents of container

200ml fill bottle

Amber glass bottle with child-resistant polypropylene screw cap incorporating a tamper evident seal (Red polyethylene).

Measuring device: 2.5ml/5ml plastic PP double-ended measuring spoon

6.6    Special disposal precautions

Not applicable

7    MARKETING AUTHORISATION HOLDER

Thornton & Ross Limited

Linthwaite

Huddersfield

HD75QH

8.    MARKETING AUTHORISATION NUMBER

PL 00240/0138

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

16/10/2006

10    DATE OF REVISION OF THE TEXT

05/03/2015