Cetirizine Hydrochloride 5mg/5ml Oral Solution
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Cetirizine Hydrochloride 5 mg/5 ml Oral Solution
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each 5 ml spoonful contains 5mg Cetirizine hydrochloride. Each 5ml spoonful also contains the following excipients:
250 mg Propylene glycol
6.75 mg Methyl parahydroxybenzoate (E218)
0.75 mg Propyl parahydroxybenzoate (E216)
2250 mg Liquid Sorbitol (E420)
For a full list of excipients, see Section 6.1.
3 PHARMACEUTICAL FORM
Oral Solution
Clear or almost clear, colourless solution with taste and odour of banana.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
For the treatment of perennial rhinitis, seasonal allergic rhinitis (hay fever) and chronic idiopathic urticaria in adults and children aged 6 years and over, and for seasonal rhinitis (hay fever) in children aged between 2 to 5 years.
4.2 Posology and method of administration
For oral use only.
Adults and children 6 years and above: 10 mg daily.
Adults and children aged 12 years and above: 10 ml once daily.
Children aged between 6 to 11 years: Either 5 ml twice daily or 10 ml once
daily.
Children aged between 2-5 years: 5 mg daily.
Either 5 ml once daily or 2.5 ml twice daily.
At present there is insufficient clinical data to recommend the use of Cetirizine in children under 2 years of age.
Elderly subjects: There is no data to suggest that the dose should be reduced in elderly patients, provided that the renal function is normal.
For 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 eliminated 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 (CLcr) in ml/min is needed. The CLcr (ml/min) may be estimated from serum creatinine (mg/dl) determination using the following formula:
CLcr = r 140-age (vears)l x weight (kg) (x 0.85 for women)
72 x serum creatinine (mg/dl)
Dosing adjustments for adult patients with impaired renal function
|
Group |
Creatinine clearance (ml/min) |
Posology 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 |
contraindicated |
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 their body weight.
Patients with hepatic impairment: no dose adjustment is needed in patients with solely hepatic impairment.
Patients with hepatic and renal impairment: dose adjustment is recommended (see Patients with moderate to severe hepatic impairment above).
4.3 Contraindications
Cetirizine is contraindicated in patients who are hypersensitive to cetirizine, to any constituent of the product, to hydroxyzine or to any piperazine derivatives.
Cetirizine is also contraindicated in patients with severe renal impairment at less than 10 ml/min creatinine clearance.
4.4 Special warnings and precautions for use
(See also section 4.7 Effects on Ability to Drive and Use Machines).
Dosage adjustment is necessary in patients with moderate or severe renal impairment (see section 4.2 Posology and Method of Administration).
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.
This medicinal product contains propylene glycol which may cause alcohollike symptoms.
Caution in epileptic patients and patients at risk of convulsions is recommended.
This medicinal product also contains Methyl parahydroxybenzoate and Propyl parahydroxybenzoate which may cause allergic reactions (possibly delayed).
Patients with rare hereditary problems of fructose intolerance should not take this medicinal product as it contains Liquid Sorbitol (E420).
For patients whose symptoms persist, it is advised to consult a doctor or pharmacist.
At therapeutic doses, no clinically signification 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.
Allergy skin tests are inhibited by antihistamines and a wash-out period (of 3 days) is required before performing them.
4.5 Interactions 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).
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.
The extent of absorption of cetirizine is not reduced with food, although the rate of absorption is decreased.
Concomitant use of cetirizine with other CNS depressants should be avoided as reduction in alertness and impairment of performance may occur.
4.6 Fertility, pregnancy and lactation
Pregnancy
For cetirizine, very rare clinical data on exposed pregnancies 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-feeding
Cetirizine is excreted in human milk at concentrations representing 25% to 90% of those measured in plasma, depending on sampling time after administration. Caution therefore should be exercised when prescribing cetirizine to lactating women.
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.
Patients intending to drive, engage in potentially hazardous activities or operate machinery should not exceed the recommended dose and should take their response to the medicinal product into account.
In sensitive patients, concurrent use with alcohol or other CNS depressants may cause additional reductions in alertness and impairment of performance.
4.8 Undesirable effects
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 Hi-receptors and is relatively free of anticholinergic activity, isolated cases of micturition difficulty, eye accommodation disorders and dry mouth have been reported. Affected patients may divide their daily dose, i.e. take as 5 mg in the morning and 5 mg in the evening.
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 Trials
Double blind controlled clinical or pharmacological trials comparing cetirizine to placebo or other antihistamines at the recommended dosage (i0 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.
|
Adverse event |
Cetirizine 10 |
Placebo |
|
(WHO-ART) |
mg (n=3260) |
(n=3061) |
|
Body as a whole - general disorders Fatigue |
1.63% |
0.95% |
|
Central and peripheral nervous system disorders | ||
|
Dizziness |
1.10% |
0.98% |
|
Headache |
7.42% |
8.07% |
|
Gastro-intestinal system disorders | ||
|
Abdominal pain |
0.98% |
1.08% |
|
Dry mouth |
2.09% |
0.82% |
|
Nausea |
1.07% |
1.14% |
|
Psychiatric disorders | ||
|
Somnolence |
9.63% |
5.00% |
|
Respiratory system 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.
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:
|
Adverse drug reactions (WHO-ART) |
Cetirizine (n=1656) |
Placebo (n=1294) |
|
Gastro-intestinal system disorders Diarrhoea |
1.0% |
0.6% |
|
Psychiatric disorders | ||
|
Somnolence |
1.8% |
1.4% |
|
Respiratory system disorders | ||
|
Rhinitis |
1.4% |
1.1% |
|
Body as a whole - general disorders 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 system disorders Very rare: thrombocytopenia Not known: haemolytic anaemia Immune system disorders:
Rare: hypersensitivity
Very rare: anaphylactic shock
Not known: bronchospasm, photosensitivity
Metabolism and nutrition disorders:
Not known: increased appetite, anorexia Psychiatric disorders Uncommon: agitation
Rare: aggression, confusion, depression, hallucination, insomnia Very rare: tic
Not known: suicidal ideation
Nervous system disorders
Uncommon: paraesthesia
Rare: convulsions, movement disorders
Very rare: syncope, dysgeusia, 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 Not known: palpitations
Gastrointestinal disorders
Uncommon: diarrhoea
Not known: vomiting, constipation Hepatobiliary disorders:
Rare: abnormal hepatic function (increased transaminases, alkaline, phosphatase, gamma-GT and bilirubin)
Skin and subcutaneous tissue disorders
Uncommon: rash, pruritus
Rare: urticaria
Very rare: angioneurotic oedema, fixed drug eruption (FDE)
Not known: alopecia 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 increase
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 at: www.mhra.gov.uk/yellowcard.
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 should be considered following ingestion of a short occurrence. In addition active charcoal should be considered if cetirizine has been ingested within 1 hour.
Cetirizine is not effectively removed by dialysis.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic classification: Piperazine derivatives R06A E07 (ATC classification system)
Cetirizine, a human metabolite of hydroxyzine, is a potent antihistamine, selective H1 receptor antagonist. The histamine-mediated ‘early’ phase of the allergic reaction is inhibited by cetirizine, which also reduces the migration of inflammatory cells and the release of mediators associated with the ‘late’ allergic responses. Effects on other receptors are negligible and consequently cetirizine is unlikely to cause undesirable anti-cholinergic and anti-serotonin effects. At the recommended therapeutic dose of 10 mg daily, impairment of CNS function has not been found to be greater than with the placebo.
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.
Studies in healthy volunteers show that cetirizine, at doses of 5 mg 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 35-day study in children aged 5 to 12, no tolerance to the antihistaminic effect (suppression of the 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 given at the high daily dose of 60 mg for seven days did not cause statistically significant prolongation of the QT interval.
At the recommended dosage, cetirizine has demonstrated that it improves the quality of life of patients with perennial and seasonal allergic rhinitis.
5.2 Pharmacokinetic properties
Cetirizine is rapidly absorbed from the gastrointestinal tract; absorption is not reduced by food, though the rate may be decreased slightly. Peak blood levels in the order of 0.3 micrograms/ml are attained between 30 and 60 minutes following administration of a 10 mg oral dose of cetirizine. Apparent plasma clearance is greater in children than in adults: the terminal elimination half-life in healthy adult volunteers ranges between 6.7 - 10.7 hours; in children 6.1 - 7.1 hours; and in children aged under 4 years 5.55 hours. Cetirizine is mainly excreted unchanged in the urine (approximately 70% over 5 days compared with 10% in the faeces). The half-life is increased in renal dysfunction: half lives of 19 and 21 hours in patients with mild to moderate renal impairment respectively have been reported. This may have implications for elderly patients. Cetirizine binds strongly to plasma proteins.
5.3 Preclinical safety data
No relevant information additional to that contained elsewhere in the SPC.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Propylene glycol Glycerol
Methyl parahydroxybenzoate (E218) Propyl parahydroxybenzoate (E216) Sodium acetate Acetic acid
Saccharin sodium Liquid Sorbitol (E420) Banana flavour Purified water
6.2 Incompatibilities
None known.
6.3 Shelf Life
Shelf life before opening -36 months Shelf life after opening - 6 months
6.4 Special precautions for storage
Do not store above 25°C.
6.5 Nature and contents of container
Type III amber glass bottles with a tamper evident screw cap having a polypropylene outer layer and a polyethylene inner layer.
Polystyrene/polyethylene measuring device.
60ml, 70ml, 80ml, 100ml, 150ml and 200 ml
6.6 Special precautions for disposal
None.
MARKETING AUTHORISATION HOLDER
7
Pinewood Laboratories Limited, Ballymacarbry,
Clonmel,
Co. Tipperary,
Ireland.
8 MARKETING AUTHORISATION NUMBER(S)
PL 04917/0068
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
11/07/2011
10 DATE OF REVISION OF THE TEXT
02/12/2015