Summary of Product Characteristics (SmPC) - Cetirizine Hydrochloride 10 mg tablets
1 NAME OF THE MEDICINAL PRODUCT
Cetirizine Hydrochloride 10 mg film-coated tablets
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each film-coated tablet contains 10mg of cetirizine dihydrochloride. Excipient(s) with known effect
Each film-coated tablet contains 77.71 mg lactose (as monohydrate). For the full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Film-coated tablet.
White, oblong, scored on one side.
The tablet can be divided into equal doses.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Cetirizine is indicated in adults and childeren aged 6 years and above:
- for the relief of nasal and ocular symptoms of seasonal and perennial allergic rhinitis.
- 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
10 mg once daily (1 tablet)
Paediatric population
The tablet formulation should not be used in children under 6 years of age as it does not allow the necessary dose adjustments.
Children aged from 6 to 12 years:
5 mg twice daily (a half tablet twice daily)
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 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.)
Dosing adjustments for adult patients with impaired renal function
Group Estimated Glomerular
Filtration Rate (eGFR)
(ml/min)
Dosage and frequency
Normal renal function
Mildly decreased renal
function
Moderately decreased
renal function
Severely decreased renal
function
End-stage renal disease-
≥ 90
60-90
30-<60
15-<30 not requiring dialysis treatment
< 15 requiring
dialysis treatment
10 mg once daily
10 mg once daily
5 mg once daily
5 mg once every 2 days
Contra-indicated
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.
Hepatic impairment
No dose adjustment is needed in patients with solely hepatic impairment. In patients with hepatic and renal impairment, adjustment of the dose is recommended (see Renal impairment above).
Method of administration
The tablets need to be swallowed with a glass of liquid.
4.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 or to hydroxyzine, to any piperazine derivatives..
Patients with end-stage renal disease with an eGFR (estimated Glomerular Filtration Rate) below 15 ml/min.
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 0.5 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.
Response to allergy skin tests is inhibited by antihistamines and a wash-out period (of 3 days) is required before performing them.
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.
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 pediatric formulation of cetirizine.
Excipients
This medicine contains 77,7 mg lactose per tablet. 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 (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).
4.6 Fertility, pregnancy and lactation
Pregnancy
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/fetal development, parturition or postnatal development. Caution should be exercised when prescribing to pregnant women.
Breast-feeding
Cetirizine passes into breast milk. A risk of side effects in breastfed infants cannot be excluded.
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.
Fertility
Limited data is available on human fertility but no safety concern has been identified.
Animal data show no safety concern for human reproduction.
4.7 Effects on 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.
4.8 Undesirable effects
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 ADRs
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 3,200 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 = 3,260) | Placebo (n = 3,061) |
General disorders and administration site conditions Fatigue | 1.63 % | 0.95 % |
| Nervous system disorders |
Dizziness Headache | 1.10 % 7.42 % | 0.98 % 8.07 % |
Gastrointestinal 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 % |
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:
Adverse reactions (WHO-ART) | Cetirizine (n = 1,656) | Placebo (n = 1,294) |
Gastrointestinal 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 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: 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, oculogyric crisis
Ear and labyrinth disorders
Not known: vertigo
Cardiac disorders
Rare: tachycardia
Gastrointestinal 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, rash
Rare: urticaria
Very rare: angioneurotic oedema, fixed drug eruption
Not known: acute generalized exanthematous pustulosis
Musculoskeletal and connective tissue disorders Not known: arthralgia, myalgia
Renal and urinary disorders
Very rare: dysuria, enuresis
Not known: urinary retention
General disorders and administration site conditions
Uncommon: asthenia, malaise
Rare: oedema
Investigations
Rare: weight increased
Description of selected adverse reactions
After discontinuation of cetirizine, pruritus (intense itching) and/or urticaria have been reported.
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: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in Google play or Apple App store.
4.9 Overdose
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 may be considered shortly after ingestion of the medicinal product.
Cetirizine is not effectively removed by haemodialysis.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Antihistamine for systemic use, Piperazine derivatives
ATC code: R06A E07
Mechanism of action
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. Pharmacodynamic effects
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 conjunctiva of atopic subjects submitted to allergen challenge.
Clinical efficacy and safety
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.
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 population
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.
5.2 Pharmacokinetic properties
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 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.
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.
Special populations
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.
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 medicinal product 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 hepatically impaired patients if concomitant renal impairment is present.
5.3 Preclinical safety data
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.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Tablet core:
cellulose, microcrystalline
lactose monohydrate
magnesium stearate
silica, colloidal anhydrous
Tablet coat
hypromellose
lactose monohydrate
macrogol 4000
titanium dioxide (E 171)
6.2 Incompatibilities
Not applicable
6.3 Shelf life
3 years.
6.4 Special precautions for storage
This medicinal product does not require any special temperature storage conditions. Store in original packaging to protect from light.
6.5 Nature and contents of container
PVC blister with aluminium foil lidding: 7, 10, 14, 20, 30, 40, 50, 60, 80, 100 and 100x1 (unit dose).
Not all pack sizes may be marketed.
6.6 Special precautions for disposal and other handling
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
7 MARKETING AUTHORISATION HOLDER
Sandoz Limited
Maxis 1
Western Road
Bracknell
RG12 1RF
United Kingdom
8. MARKETING AUTHORISATION NUMBER
PL 04416/0381
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
28/04/2008
10 DATE OF REVISION OF THE TEXT
13/04/2026