PIRITEZE CHILDRENS HAYFEVER & ALLERGY 1 MG / ML SYRUP, PIRITEZE ALLERGY 1 MG / ML SYRUP - summary of medicine characteristics

1 NAME OF THE MEDICINAL PRODUCT

Piriteze Allergy 1mg/ml Syrup

Piriteze Children’s Hayfever & Allergy 1mg/ml Syrup

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

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

Excipients:

Piriteze Syrup contains 315mg sorbitol per ml.

For full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

1mg/ml Syrup. Clear and colourless liquid with a slightly sweet taste and a banana flavour.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

In adults and children 6 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 6 to 12 years: 5mg 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:

CLcr  =    [140 – age(years)] x weight (kg) (x 0.85 for woman)

72 x serum creatinine (mg/dl)

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 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

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 6 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 drugdrug 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 Fertility, 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 excreted 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:

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:

Post-marketing experience

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).

Skin reactions occurring 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: 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 400–500 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.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Piperazine derivatives, ATC code: R06A E07

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

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

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

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.

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

In a placebo-controlled study, cetirizine give at the high daily dose of 60 mg 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.

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

Liquid Sorbitol (non-crystallising) (E420)

Methyl Parahydroxybenzoate (E218)

Propyl Parahydroxybenzoate (E216)

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

70ml fill bottle.

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

Measuring device: 5 ml plastic PP measuring spoon graduated at 2.5 ml

6.6 Special precautions for disposal

No special requirements.