Piriteze Allergy Tablets

10 mg of cetirizine hydrochloride

For excipients, see 6.1.

Film coated tablets.

White to off white capsule-shaped tablet, debossed with C10 on one side and a deep breakline on the other.

In adults and paediatric patients 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.

Children aged from 6 to 12 years: 5mg twice daily (a half tablet twice daily).

Adults and adolescents over 12 years if age: 10 mg once daily (1 tablet 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 (CL_cr) in ml/min is needed. The CL_cr ml/min may be estimated from serum creatinine (mg/dl) determination using the following formula:

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).

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.

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency of glucose-galactose malabsorption should not take cetirizine film-coated tablets.

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

The use of the film-coated tablet formulation is not recommended in children aged less than 6 years since this formulation does not allow for appropriate dose adaptation.

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 perfomed, 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.

Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal / foetal development, parturition or post-natal development (see 'Preclinical safety data').

There are no adequate data from the use of cetirizine in pregnant women.

Cetirizine hydrochloride should not be used during pregnancy unless clearly necessary.

Cetirizine is contraindicated in lactating women as it is excreted in breast milk.

Studies in healthy volunteers at 20 and 25mg/day have not revealed adverse effects on alertness or reaction time. However, patients are advised not to exceed the recommended dose if driving or operating machinery even though cetirizine has no or negligible influence on these parameters.

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 antichloinergic 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 trails

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

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. For the less frequently reported undesirable effects, the estimated frequencies (uncommon: 1/1,000 to 1/100, rare: 1/10,000 to 1/1,000, very rare: 1/10,000) are made based on post-marketing experience.

Blood and lymphatic disorders:

Very rare: thrombocytopenia

Immune system disorders:

Rare: hypersensitivity

Very rare: anaphylactic shock

Psychiatric disorders:

Uncommon: agitation

Rare: aggression, confusion, depression, hallucinations, insomnia

Very rare: tic

Nervous system disorders:

Uncommon: paraesthesia

Rare: convulsions, movement disorders

Very rare; dysgeusia, syncope, tremor, dystonia, dyskinesia

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 phosphataes, γ-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

Drowsiness can be a symptom of overdose. In children, agitation can occur.

In the case of massive overdose, gastric lavage should be performed together with the usual supportive measures.

To date, there is no specific antidote.

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 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 glare 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.

Peak blood levels in the order of 0.3μg/ml are reached within about one hour after the oral administration of cetirizine. The terminal half-life is approximately ten hours in adults and six hours in children aged 6 - 12 years.

This is consistent with the urinary excretion half-life of the drug. The cumulative urinary excretion represents about two thirds of the dose given for both adults and children.

Consequently, the apparent plasma clearance in children is higher than that measured in adults. Plasma levels are linearly related to the dose given. A high proportion of cetirizine is bound to human plasma proteins.

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

Preclinical results were observed only at exposures considered sufficiently in excess of the maximum human exposure indicating little relevance to clinical use.

Tablet core:

Microcrystalline cellulose

Lactose monohydrate

Colloidal anhydrous silica

Magnesium stearate

Coating:

Hypromellose (E464)

Macrogol 4000

Titanium dioxide (E171)

Polydextrose

Not applicable.

36 months.

No special precautions for storage.

Transparent or white opaque PVC/PVdC – aluminium blister packs containing 4, 7, 12 or 14 film-coated tablets.

Not applicable

Beecham Group PLC

Trading as GlaxoSmithKline Consumer Healthcare

980 Great West Road

Brentford

Middlesex

TW8 9GS

United Kingdom

PL 00079/0398

25 September 2003 / 13 March 2009

24 November 2009