This information is intended for use by health professionals

1. Name of the medicinal product

POLLENSHIELD HAYFEVER RELIEF

Cetirizine hydrochloride 10mg Film-coated Tablets

2. Qualitative and quantitative composition

Each tablet contains 10mg Cetirizine hydrochloride.

Excipient with known effect: Each tablet contains 117.00mg lactose monohydrate

For the full list of excipients, see section 6.1

3. Pharmaceutical form

Film-coated tablet (Tablets).

Film-coated, white or almost white convex, elliptical, tablets. 5.7 x 11.4mm. The letter “C” on one side and the letters “J” and “E” on either side of a central division line on the reverse.

4. Clinical particulars
4.1 Therapeutic indications

In adults and paediatric patients 6 year 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.

4.2 Posology and method of administration

Posology

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

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

Dosing adjustments for adult patients with impaired renal function

Group

Creatinine clearance (ml/min)

Dosage and frequency

Normal

≥80

10mg once daily

Mild

50 – 79

10mg once daily

Moderate

30 – 49

5mg once daily

Severe

<30

5mg once every 2 days

End-stage renal disease

Patients undergoing dialysis

<10

Contra-indicated

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).

Method of Administration

For oral use.

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

4.3 Contraindications

• Hypersensitivity to the active substance, hydroxyzine, any piperazine derivatives or to any of the excipients listed in section 6.1.

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

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 0.5g/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.

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.

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.

This product conatins lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose- galactose malabsorption should not take this medicine.

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 (400mg/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

Pregnancy

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/fetal development, parturition or postnatal development (see section 5.3). 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 cetirizine to lactating women.

4.7 Effects on ability to drive and use machines

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. 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 dihydrochloride.

Clinical trials

Double blind controlled clinical or pharmacoclinical trials comparing cetirizine to placebo or other antihistamines at the recommended dosage (10mg 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 10mg in the placebo-controlled trials at rates of 1.0% or greater:

Adverse event

Cetirizine 10mg

Placebo

(WHO-ART)

(n= 3260)

(n = 3061)

General disorders and administration site conditions

Fatigue

1.63%

0.95%

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, thoracic and mediastinal 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 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:

Adverse event (WHO-ART)

Cetirizine 10mg

(n=1656)

Placebo

(n =1294)

Gastro-intestinal system disorders Diarrhoea

1.0%

0.6%

Psychiatric disorders Somnolence

1.8%

1. 4%

Respiratory thoracic and mediastinal disorders Rhinitis

1.4%

1.1%

General disorders and administration site conditions

Fatigue

1.0%

0.3%

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.

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); very rare (<1/10,000), not known (cannot be estimated from the available data).

Uncommon

Rare

Very rare

Not known

Blood and lymphatic disorders:

thrombocytopenia

Immune system disorders:

hypersensitivity

anaphylactic shock

Metabolism and nutrition disorders:

increased appetite

Psychiatric disorders:

agitation

aggression, confusion, depression, hallucination, insomnia

tic

suicidal ideation, nightmares

Nervous system disorders:

paraesthesia

convulsions, movements disorders

dysgeusia, syncope, tremor, dystonia, dyskinesia

amnesia, memory impairment

Eye disorders:

accommodation disorder, blurred vision, oculogyration

Ear and labyrinth disorders:

vertigo

Cardiac disorders:

tachycardia

Gastro-intestinal disorders:

diarrhoea

Hepatobiliary disorders:

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

hepatitis

Skin and subcutaneous tissue disorders:

pruritus, rash

urticaria

angioneurotic oedema, fixed drug eruption

Acute generalized exanthematous pustulosis (AGEP)

Musculoskeletal and connective tissue disorder

Arthralgia

Renal and urinary disorders:

dysuria, enuresis

urinary retention (see section Warnings and Precautions)

General disorders and administration site conditions:

asthenia, malaise

oedema

Investigations:

weight increased

Skin reactions occuring 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; website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9 Overdose

Toxicity: 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.

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 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 H1receptors. In vitro receptor binding studies have shown no measurable affinity for other than H1receptors.

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.

Studies in healthy volunteers show that cetirizine, at doses of 5 and 10mg 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 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.

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 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 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.

5.2 Pharmacokinetic properties

The steady - state peak plasma concentrations is approximately 300ng/ml and is achieved within 1.0 ± 0.5 h. No accumulation is observed for cetirizine following daily doses of 10mg for 10 days. The distribution of pharmacokinetic parameters such as peak plasma concentration (Cmax) and area under curve (AUC), is unimodal in human volunteers.

Absorption

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 0.50l/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. About two third of the dose are excreted unchanged in urine. The terminal half-life is approximately 10 hours.

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

Special populations

Elderly: Following a single 10mg 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.

Children, infants and toddlers: 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

Renal impairment: The pharmacokinetics of the drug were similar in patients with mild impairment (creatinine clearance higher than 40ml/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 7ml/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 normals. 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 20mg 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

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.

6. Pharmaceutical particulars
6.1 List of excipients

Tablet core:

Microcrystalline cellulose (E460), lactose monohydrate, crospovidone, colloidal anhydrous silica, magnesium stearate.

Film coat:

Hypromellose (E464), macrogol stearate, microcrystalline cellulose (E460), propylene glycol, titanium dioxide (E171).

6.2 Incompatibilities

None known.

6.3 Shelf life

3 years.

6.4 Special precautions for storage

Blister pack:

Do not store above 25°C.

Store in the original package

6.5 Nature and contents of container

Blister pack

(i) 60µm PVC/45µm Al/25µm OPA

(ii) 20µm Al

Blister pack: 4, 5, 7

Not all pack sizes may be marketed

6.6 Special precautions for disposal and other handling

Not applicable.

7. Marketing authorisation holder

Accord-UK Ltd

(Trading style: Accord)

Whiddon Valley

Barnstaple

Devon

EX32 8NS

8. Marketing authorisation number(s)

PL 0142/0606

9. Date of first authorisation/renewal of the authorisation

June 2004

10. Date of revision of the text

25/10/2019

Legal status

GSL