n adults and children 6 years and above:

§ Rizino is indicated for the relief of nasal and ocular symptoms of seasonal and perennial allergic rhinitis.

§ Rizino is indicated for the relief of chronic idiopathic urticaria.

Posology

Children aged from 6 to 12 years: 5mg twice daily (one teaspoonful twice daily).

Adults and adolescents over 12 years if age: 10 mg once daily (2 teaspoonful 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:

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, 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).

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.

The use of Rizino is not recommended in children aged less than 6 years.

Rizino contains methyl paraben and propyl paraben may cause allergic reactions (possibly delayed).

Rizino contains Sorbitol. Patients with rare hereditary problems of fructose intolerance, should not take cetirizine

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

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.

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/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.

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.

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 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

Metabolism and nutrition disorders:

§ Not known: increased appetite

Psychiatric disorders:

§ Uncommon: agitation

§ Rare: aggression, confusion, depression, hallucinations, insomnia

§ Very rare: tic

§ Not known: suicidal ideation

Nervous system disorders:

§ Uncommon: paraesthesia

§ Rare: convulsions, movement disorders

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

§ Unknown: 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: 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

§ Not known: urinary retention (see section warnings and precautions)

General disorders and administration site conditions:

§ Uncommon: asthenia, malaise

§ Rare: oedema

Investigations:

§ Rare: weight increased

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.

Cetirizine is not effectively removed by dialysis.

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.

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.

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

List of excipients
Glycerol. 
Sorbitol. 
Propylene glycol. 
Methyl paraben. 
Propyl paraben. 
Saccharin sodium. 
Povidone. 
Citric acid anhydrous. 
Sodium citrate. 
Sodium chloride. 
Raspberry flavor. 

Not applicable.

Keep at temperature 15 - 25°C, 

arton box containing one amber plastic bottle (containing 100 ml of syrup) and a pamphlet. 

Not special requirements.