CETIRIZINE HYDROCHLORIDE 10 MG TABLETS, ALMUS HAYFEVER & ALLERGY RELIEF 10 MG TABLETS - summary of medicine characteristics

1 NAME OF THE MEDICINAL PRODUCT

Cetirizine Hydrochloride 10 mg Tablets

Almus Hayfever & Allergy Relief 10mg Tablets

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains Cetirizine hydrochloride 10 mg.

Excipient: This product contains 101.83 mg lactose per tablet

For a full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Film-coated tablet (tablets).

White circular biconvex film-coated tablets, embossed ‘A’ on one side and a deep score on the other.

The tablet can be divided into equal halves.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

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 symptoms of chronic idiopathic urticaria.

4. CLINICAL PARTICULARS

4.2. Posology and Method of Administration

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

Adults and adolescents over 12 years of age: 10 mg once daily (1 tablet).

Older people: 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 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 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 women)

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, his 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 Patients with moderate to severe renal impairment above).

The tablets need to be swallowed with a glass of liquid.

4. CLINICAL PARTICULARS

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

4.

CLINICAL PARTICULARS

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

Allergy skin tests are inhibited by antihistamines and a washout period (of 3 days) is required before performing them.

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Paediatric population

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.

4. CLINICAL PARTICULARS

4.5. Interactions 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.

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 effects of alcohol (0.5g/L blood levels).

4. CLINICAL PARTICULARS

4.6. Fertility, Pregnancy and Lactation

Pregnancy

For cetirizine, prospectively collected data on pregnancy outcomes do not suggest potential for maternal or foteal/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 be exercised when prescribing to pregnant women.

Breast Feeding

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 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. CLINICAL PARTICULARS

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. 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.

4. CLINICAL PARTICULARS

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 dihydrochloride

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:

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 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 the MedDRA System Organ Class and by estimated frequency based on post-marketing exposure. 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

Metabolic and nutritional disorders:

Not known:         increased appetite

Psychiatric disorders:

Uncommon:        agitation

Rare:                ag­gression, confusion, depression, hallucination, insomnia

Very rare:            tics

Not known:         Suicidal ideation

Nervous system disorders:

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, 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

Not known:         urinary retention

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 authorization 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 system at www.mhra.uk/yellowcard.

By reporting side effects you can help provide more information on the safety of this medicine.

4. CLINICAL PARTICULARS

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 should be considered following ingestion of a short occurrence. Cetirizine is not effectively removed by haemodialysis.

5. PHARMACOLOGICAL PROPERTIES

5.1. Pharmacodynamic Properties

Pharmacotherapeutic group: Antihistamine for systemic use, piperazine derivatives, ATC code: R06 AE07

Mechanism of action

Cetirizine, a human metabolite of hydroxyzine, is a potent and selective antagonist of peripheral H1receptors. In vitro receptor binding studies have shown no measurable affinity for 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 10 mg 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 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 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 given 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

Paediatric population

In a 35-day study in children aged 5 to 12, no tolerance to the antihistaminic 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. PHARMACOLOGICAL PROPERTIES

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. No accumulation is observed for cetirizine following daily doses of 10 mg for 10 days. The distribution of pharmacokinetic parameters, such as peak plasma concentration (Cmax) and area under curve (AUC), is unimodal in human volunteers. 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.

Linearity/non-linearity

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

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

Special populations

Older people: 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 612 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

Renally impaired: The pharmacokinetics of the drug were 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 hemodialysis (creatinine clearance less than 7 ml/min) given a single oral 10 mg dose of cetirizine had a 3-fold increase in half-life and a 70 % decrease in clearance compared to normals. Cetirizine was poorly cleared by haemodialysis.

Dosing adjustment is necessary in patients with moderate or severe renal impairment (see section 4.2).

Hepatically impaired: 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 hepatically impaired patients if concomitant renal impairment is present.

5.3 Preclinical safety data

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

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Lactose Monohydrate

Microcrystalline Cellulose

Maize Starch

Colloidal Anhydrous Silica

Magnesium Stearate

Talc

Film coat contains:

Hypromellose

Lactose monohydrate

Titanium Dioxide E171

Macrogol 4000

Sodium Citrate

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

Three years.

6.4 Special precautions for storage

This medicinal product does not require any special storage conditions.

6.5 Nature and contents of container

Blister strips composed of transparent PVC and Aluminium foil.

Pack sizes: 7, 14, 21, 28, or 30 tablets.

6.6 Special precautions for disposal

No special requirements.

PL 08977/0046

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

30/06/2011