Zyrrigin

Each film coated tablet contains: Cetirizine dihydrochloride, BP 10 mg.
Each 5 mL contains: Cetirizine dihydrochloride, BP 5 mg.

Pharmacology: 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.
Pharmacokinetics: Absorption: The steady-state peak plasma concentrations is approximately 300 ng/mL and is achieved within 1.0 ± 0.5 hour. The distribution of pharmacokinetic parameters such as peak plasma concentration (C_max) 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 healthy volunteers. Cetirizine was poorly cleared by hemodialysis. Dosing adjustment is necessary in patients with moderate or severe renal impairment.
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 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.

For the relief of nasal and ocular symptoms of seasonal and perennial allergic rhinitis; and symptoms of chronic idiopathic urticaria.

Oral.
Posology: See Table 1.

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Special population: Elderly: Data do not suggest that the dose needs to be reduced in elderly subjects provided that the renal function is normal.
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 Pharmacology under Actions), in cases where no alternative treatment can be used, the dosing intervals must be individualized according to renal function. Refer to Table 2 and adjust the dose as indicated. To use the 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: See equation and Table 2.

Click on icon to see table/diagram/image


Click on icon to see table/diagram/image

Hepatic impairment: No dose adjustment is needed in patients with solely hepatic impairment. In patients with hepatic impairment and renal impairment, adjustment of the dose is recommended (see Renal impairment previously).
Pediatric population: The tablet formulation should not be used in children under 6 years of age as it does not allow the necessary dose adjustments.
In pediatric 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.
Method of administration: The tablets need to be swallowed with a glass of liquid. The solution can be swallowed as such.

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, diarrhea, 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. Alternatively consider activated charcoal. Cetirizine is not effectively removed by hemodialysis.

Hypersensitivity to Cetirizine, 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 or 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 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 is recommended in epileptic patients and patients who are at risk of convulsions.
Response to allergy skin tests are inhibited by antihistamines and a wash-out 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 Cetirizine film-coated tablets.
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 be resolved when the treatment is restarted.
Effects on the 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. However, patients who experience somnolence should refrain from driving, engaging in potentially hazardous activities or operating machinery. They should not exceed the recommended dose and should take their response to the medicinal product into account.
Use in 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. It is recommended to use a pediatric formulation of Cetirizine.
For syrup, due to the amount of some excipients in the formulation, the use of the product is not recommended in children aged less than 2 years.

Pregnancy: For Cetirizine prospectively collected data on pregnancy outcomes do not suggest potential for maternal or fetal/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.
Breastfeeding: Cetirizine is excreted in human milk at concentrations representing 25% to 90% those measured in plasma, depending on sampling time after administration. Therefore, caution should be exercised when prescribing Cetirizine 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.

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.
Metabolism and nutrition disorders: Not known: Increased appetite.
Psychiatric disorders: Uncommon: Agitation. Rare: Aggression, confusion, depression, hallucinations, insomnia. Very rare: Tics. Not known: Suicidal ideation.
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.
Gastrointestinal disorders: Uncommon: Diarrhea.
Hepatobiliary disorders: Rare: Hepatic function abnormal (increased transaminases, alkaline phosphatases, γ-GT and bilirubin).
Skin and subcutaneous tissue disorders: Uncommon: Pruritus, rash. Rare: Urticaria. Very rare: Angioneurotic edema, fixed drug eruption. Not known: Acute generalized exanthematous pustulosis.
Musculoskeletal and connective tissue disorders: Not known: Arthralgia.
Renal and urinary disorders: Very rare: Dysuria, enuresis. Not known: Urinary retention.
General disorders and administration site condition: Uncommon: Asthenia, malaise. Rare: Edema.
Investigations: Rare: Weight increased.

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.
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).

Store at temperatures not exceeding 30°C.

Antihistamines & Antiallergics

R06AE07 - cetirizine ; Belongs to the class of piperazine derivatives used as systemic antihistamines.

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