For the relief of

·         Nasal and ocular symptoms of seasonal and perennial allergic rhinitis.

·         Symptoms of chronic idiopathic urticaria.

Posology

Adults

10 mg (20 drops or 10 ml of oral solution or 1 tablet) once daily.

A 5 mg starting dose (10 drops or 5 ml of oral solution or half of the tablet) may be proposed if this leads to satisfactory control of the symptoms.

Children

·         Children aged from 2 to 6 years

 (2.5 ml of oral solution) twice daily.

·         Children aged from 6 to 12 years

 (5 ml of oral solution) twice daily.

·         Children over 12 years of age

 (10 ml of oral solution) once daily.

Elderly

Data does not suggest that the dose needs to be reduced in elderly subjects provided that the renal function is normal.

Renal impairment

Since cetirizine is mainly excreted via renal route, 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:

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, age and body weight of the patient.

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 Renal Impairment above).

Method of administration:

The solution can be swallowed as such.

Route of Administration

For oral use.

Alcohol

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 (see Section Interactions).

Increased risk of urinary retention

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.

Patients at risk of convulsions

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

Skin reactions

Pruritus and/or urticaria may occur when cetirizine is stopped, even if those symptoms were not present before treatment initiation. In some cases, the symptoms may be intense and may require treatment to be restarted. The symptoms should resolve when the treatment is restarted.

Children

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.

Allergy skin tests

Allergy skin tests are inhibited by antihistamines and a wash-out period of 3 days is recommended before performing them.

Food

The extent of absorption of cetirizine is not reduced with food, although the rate of absorption is decreased.

Due to the pharmacokinetic, pharmacodynamic and tolerance profile of cetirizine, no interactions are expected with this antihistamine. Neither pharmacodynamic nor significant pharmacokinetic interaction was reported in drug-drug interactions studies performed, notably with pseudoephedrine or theophylline (400 mg/day).

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 (0.5 g/L blood levels) (see Section Warnings and Precautions).

Fertility

Limited data is available on human fertility but no safety concern has been identified.

Animal data show no safety concern for human reproduction.

Pregnancy

Caution should be exercised when prescribing to pregnant women.

For cetirizine prospectively collected data on pregnancy outcomes do not suggest potential for maternal or foetal/embryonic toxicity above background rates.

Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development. 

Lactation

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.

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.

However, patients who experience somnolence should refrain from driving, engaging in potentially hazardous activities or operating machinery.

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.

Clinical Trial Data

Clinical studies have shown that cetirizine at the recommended dosage has minor adverse 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.

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.

Paediatric population

Adverse reactions at rates of 1 % or greater in children aged from 6 months to 12 years, included in placebo-controlled clinical trials are:

Post-marketing experience

Adverse drug reactions (ADRs) are listed below by MedDRA system organ class and by frequency.

Frequencies are defined as:

Very common ≥1/10

Common ≥1/100 to <1/10

Uncommon ≥1/1000 to <1/100

Rare ≥1/10000 to <1/1000

Very rare <1/10000

Not known (cannot be estimated from the available data).

Blood and lymphatic system disorders

·         Very rare: thrombocytopenia.

Immune system disorders

·         Rare: hypersensitivity.

·         Very rare: anaphylactic shock.

Metabolism and nutrition disorders

·         Not known: increased appetite.

Psychiatric disorders

·         Uncommon: agitation.

·         Rare: aggression, confusion, depression, hallucination, insomnia.

·         Very rare: tics.

·         Not known: suicidal ideation, nightmare.

Nervous system disorders

·         Uncommon: paraesthesia.

·         Rare: convulsions.

·         Very rare: dysgeusia, syncope, tremor, dystonia, dyskinesia.

·         Not known: amnesia, memory impairment.

Eye disorders

·         Very rare: accommodation disorder, blurred vision, oculogyration.

Ear and labyrinth disorders.

·         Not known: vertigo.

Cardiac disorders

·         Rare: tachycardia

Gastro-intestinal disorders

·         Uncommon: diarrhea

Hepatobiliary disorders

·         Rare: hepatic function abnormal (transaminases increased, blood bilirubin increased, blood alkaline phosphatase increased, gamma-glutamyl transferase increased)

Skin and subcutaneous tissue disorders

·         Uncommon: pruritus, rash.

·         Rare: urticaria.

Renal and urinary disorders

·         Very rare: dysuria, enuresis.

·         Not known: urinary retention (See section Warning and precaution).

General disorders and administration site conditions

·         Uncommon: asthenia, malaise.

·         Rare: oedema.

Investigations

·         Rare: weight increased.

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).

To report any side effect(s):

•Saudi Arabia:

The National Pharmacovigilance Center (NPC):

SFDA Call Center: 19999

E-mail: npc.drug@sfda.gov.sa

Website: https://ade.sfda.gov.sa

•United Arab of Emirates:

Pharmacovigilance and Medical Device Section

P.O. Box: 1853, Tel: 80011111

Email: pv@mohap.gov.ae

Drug Department, Ministry of Health & Prevention

Dubai-UAE.

•Other GCC States:

Please contact the relevant competent authority.

Symptoms and signs

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.

Treatment

There is no known specific antidote to cetirizine.

Should overdose occur, symptomatic or supportive treatment is recommended.

Cetirizine is not effectively removed by haemodialysis.

Management should be as clinically indicated or as recommended by the national poisons centre, where available.

Pharmacotherapeutic group

Antihistamines for systemic use, piperazine derivatives, ATC Code: R06AE07

Mechanism of Action and Pharmacodynamic effects

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 inflammatory cells, notably eosinophils, in the skin and conjunctiva of atopic subjects submitted to antigen 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. The onset of activity after a single 10 mg dose occurs within 20 minutes in 50 % of the subjects and within one hour in 95 %.  This activity persists for at least 24 hours after a single administration. 

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.

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.

Absorption

The steady - state peak plasma concentrations is approximately 300 ng/ml and is achieved within 1.0 ± 0.5 h..The distribution of pharmacokinetic parameters such as peak plasma concentration (Cmax) and area under curve (AUC) is unimodal.

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.

Elimination

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

Linearity/Non-linearity

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

Renal impairment: The pharmacokinetics of the drug was 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).

Hepatic impairment: 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 patients with hepatic impairment if concomitant renal impairment is present.

Elderly: 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.

Pediatric population: 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.

Not relevant for this product.

Non-clinical information

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.

The other ingredients are sorbitol powder, glycerin, propylene glycol, sodium saccharin (fine powder), methyl paraben, banana liquid flavor, trisodium citrate 2H2O.

None.

Store below 30. Do not refrigerate.

After opening, the solution should be used within 20 days.

Finallerg ^®oral solution: is a clear colorless solution with banana odor, presented in amber glass bottles type III, 100 ml, with white polypropylene child resistant screw cap with low density polyethylene transparent plug and white sealing ring embossed drawing on top explaining how to open the cap, intended for oral use. Pack size: 100 ml.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.