- 1. Name of the medicinal product
- 2. Qualitative and quantitative composition
- 3. Pharmaceutical form
- 4. Clinical particulars
- 4.1 Therapeutic indications
- 4.2 Posology and method of administration
- 4.3 Contraindications
- 4.4 Special warnings and precautions for use
- 4.5 Interaction with other medicinal products and other forms of interaction
- 4.6 Fertility, pregnancy and lactation
- 4.7 Effects on ability to drive and use machines
- 4.8 Undesirable effects
- 4.9 Overdose
- 5. Pharmacological properties
- 5.1 Pharmacodynamic properties
- 5.2 Pharmacokinetic properties
- 5.3 Preclinical safety data
- 6. Pharmaceutical particulars
- 6.1 List of excipients
- 6.2 Incompatibilities
- 6.3 Shelf life
- 6.4 Special precautions for storage
- 6.5 Nature and contents of container
- 6.6 Special precautions for disposal and other handling
- 7. Marketing authorisation holder
- 8. Marketing authorisation number(s)
- 9. Date of first authorisation/renewal of the authorisation
- 10. Date of revision of the text
Posology10 mg once daily (1 tablet)Elderly Patients: 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:Dosing adjustments for adult patients with impaired renal function
|Group||Creatinine clearance (ml/min)||Dosage and frequency|
|Normal||≥80||10 mg once daily|
|Mild||50 79||10 mg once daily|
|Moderate||30 49||5 mg once daily|
|Severe||<30||5 mg once every 2 days|
|End-stage renal disease - Patients undergoing dialysis||<10||Contra-indicated|
Paediatric populationThe tablet formulation should not be used in children under 6 years of age as it does not allow the necessary dose adjustments.Children aged 6 to 12 years: 5 mg twice daily (a half tablet twice daily).Adolescents above 12 years: 10 mg once daily (1 tablet).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.
Method of administrationThe tablets need to be swallowed with a glass of liquid.
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. It is recommended to use a paediatric formulation of cetirizine.
PregnancyFor cetirizine prospectively collected data on pregnancy outcomes do not suggest potential for maternal or foetal/ embryonic toxicity above background rates. 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 postnatal development. Caution should be exercised when prescribing to pregnant women.
Breast-feedingCetirizine 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.
FertilityLimited data is available on human fertility but no safety concern has been identified.Animal data show no safety concern for human reproduction.
Clinical studies• Overview 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.• Listing of ADRsDouble 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:
|Adverse reactions (WHO-ART)||Cetirizine 10 mg (n= 3260)||Placebo (n = 3061)|
|General disorders and administration site conditions Fatigue||1.63 %||0.95 %|
|Nervous system disorders Dizziness Headache||1.10 % 7.42 %||0.98 % 8.07 %|
|Gastro-intestinal disorders Abdominal pain Dry mouth Nausea||0.98 % 2.09 % 1.07 %||1.08 % 0.82 % 1.14 %|
|Psychiatric disorders Somnolence||9.63 %||5.00 %|
|Respiratory, thoracic and mediastinal disorders Pharyngitis||1.29 %||1.34 %|
Paediatric populationAdverse drug reactions at rates of 1 % or greater in children aged from 6 months to 12 years, included in placebo-controlled clinical trials are:
|Adverse reactions (WHO-ART)||Cetirizine (n= 1656)||Placebo (n = 1294)|
|Gastro-intestinal 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 experienceIn 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 MedDRA System Organ Class and by estimated frequency based on post-marketing experience.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: hypersensitivityVery rare: anaphylactic shock
Metabolism and nutrition disorders:Not known: increased appetite
Psychiatric disorders:Uncommon: agitationRare: aggression, confusion, depression, hallucination, insomniaVery rare: ticsNot known: suicidal ideation
Nervous system disorders:Uncommon: paraesthesiaRare: convulsions, movement disorders. 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: diarrhoea
Hepatobiliary disorders:Rare: hepatic function abnormal (increased transaminases, alkaline phosphatase, γ-GT and bilirubin)Not known: Hepatitis
Skin and subcutaneous tissue disorders:Uncommon: pruritus, rashRare: urticariaVery rare: angioneurotic oedema, fixed drug eruption
Renal and urinary disorders:Very rare: dysuria, enuresisNot known: urinary retention (see section Warnings and Precautions)
General disorders and administration site conditions:Uncommon: asthenia, malaiseRare: oedema
Investigations:Rare: weight increased
No data available
Reporting of suspected adverse reactionsReporting 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 Yellow card scheme at www.mhra.gov.uk/yellowcard.
ManagementThere 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.
Mechanism of actionCetirizine, 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.
Pharmacodynamic effectsIn 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 safetyStudies 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 populationIn 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.
AbsorptionThe steady - state peak plasma concentration 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 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.
DistributionThe 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.
BiotransformationCetirizine does not undergo extensive first pass metabolism.
EliminationThe 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-linearityCetirizine exhibits linear kinetics over the range of 5 to 60 mg.
Special populationsElderly: 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 younger 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 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 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.
Bristol Laboratories Ltd
Bristol House , Unit 3, Canalside, Northbridge Road, Berkhamsted, Hertfordshire, HP4 1EG
+44 (0) 1442 873 717
+44 (0) 1442 873 717
+44 (0) 1442 200 922
+44 (0) 1442 200 922
+44 (0) 1442 200 922