- 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 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
- 11. Dosimetry
- 12. Instructions for preparation of radiopharmaceuticals
Adults and adolescents 12 years and aboveThe daily recommended dose is 5 mg (one film-coated tablet) once daily.
Children aged 6 to 12 yearsThe daily recommended dose is 5 mg (one film-coated tablet) daily. Levocetirizine is not recommended for use in children below age 6 due to insufficient data on safety and efficacy.
ElderlyFor the time being, there is no data to suggest that the dose needs to be reduced in elderly patients 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 impairement. Since levocetirizine 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||One tablet daily|
|Mild||50 - 79||One tablet daily|
|Moderate||30 - 49||One tablet every two days|
|Severe||30||One tablet every three days|
|End-stage renal disease - patients undergoing dialysis||10||Contra-indicated|
Patients with hepatic impairmentNo dose adjustment is needed in patients with solely hepatic impairment.
Patients with hepatic impairment and renal impairmentDose adjustment is recommended (see Patients with moderate to severe renal impairment above).
|Blood and lymphatic system disorders||Thrombocytopenia|
|Immune system disorders||Hypersensitivity||Anaphylactic shock|
|Psychiatric disorders||Somnolence||Agitation||Aggression Confusion Depression Hallucination Insomnia||Tic|
|Nervous system disorders||Dizziness Headache||Paraesthesia||Convulsions Movement disorders||Dysgeusia Syncope Tremor Dystonia Dyskinesia|
|Eye disorders||Accomodation disorder Blurred vision Oculogyration|
|Respiratory, thoracic and mediastinal disorders||Pharyngitis Rhinitis*|
|Gastrointestinal disorders||Abdominal pain Dry mouth Nausea||Diarrhoea|
|Hepatobiliary disorders||Hepatic function abnormal (increased transaminases, alklaline phosphatise, γ-GT and bilirubin)|
|Skin and subcutaneous tissue disorders||Pruritus Rash||Urticaria||Angioneurotic oedema Fixed drug eruption|
|Renal and urinary disorders||Dysuria Enuresis|
|General disorders and administration site conditions||Fatigue||Asthenia Malaise||Oedema|
SymptomsSymptoms observed after an overdose of levocetirizine 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 of overdoses There is no known specific antidote to levocetirizine.Should overdose occur, symptomatic or supportive treatment is recommended. Gastric lavage should be considered following ingestion of a short occurrence. Levocetirizine is not effectively removed by dialysis.
Pharmacokinetic / pharmacodynamic relationship5 mg levocetirizine provides a similar pattern of inhibition of histamine-induced wheal and flare as 10 mg cetirizine. As for cetirizine, the action on histamine-induced skin reactions was out of phase with the plasma concentrations. ECGs did not show relevant effects of levocetirizine on QT interval.
AbsorptionLevocetirizine is rapidly and extensively absorbed following oral administration. Peak plasma concentrations are achieved 0.9 h after dosing. Steady state is achieved after two days. Peak concentrations are typically 270 ng/ml and 308 ng/ml following a single and a repeated 5 mg o.d. dose, respectively. The extent of absorption is dose-independent and is not altered by food, but the peak concentration is reduced and delayed. Distribution: No tissue distribution data are available in humans, neither concerning the passage of levocetirizine through the blood-brain-barrier. In rats and dogs, the highest tissue levels are found in liver and kidneys, the lowest in the CNS compartment. Levocetirizine is 90% bound to plasma proteins. The distribution of levocetirizine is restrictive, as the volume of distribution is 0.4 l/kg.
BiotransformationThe extent of metabolism of levocetirizine in humans is less than 14% of the dose and therefore differences resulting from genetic polymorphism or concomitant intake of enzyme inhibitors are expected to be negligible. Metabolic pathways include aromatic oxidation, N- and O- dealkylation and taurine conjugation. Dealkylation pathways are primarily mediated by CYP 3A4 while aromatic oxidation involved multiple and/or unidentified CYP isoforms. Levocetirizine had no effect on the activities of CYP isoenzymes 1A2, 2C9, 2C19, 2D6, 2E1 and 3A4 at concentrations well above peak concentrations achieved following a 5 mg oral dose. Due to its low metabolism and absence of metabolic inhibition potential, the interaction of levocetirizine with other substances, or vice-versa, is unlikely.
EliminationThe plasma half-life in adults is 7.9 ± 1.9 hours. The mean apparent total body clearance is 0.63 ml/min/kg. The major route of excretion of levocetirizine and metabolites is via urine, accounting for a mean of 85.4% of the dose. Excretion via feces accounts for only 12.9% of the dose. Levocetirizine is excreted both by glomerular filtration and active tubular secretion.
Renal impairmentThe apparent body clearance of levocetirizine is correlated to the creatinine clearance. It is therefore recommended to adjust the dosing intervals of levocetirizine, based on creatinine clearance in patients with moderate and severe renal impairment. In anuric end stage renal disease subjects, the total body clearance is decreased by approximately 80% when compared to normal subjects.
Tablet coreLactose monohydrateCellulose microcrystallineMagnesium stearate (E572)
Film-coatingHypromellose (E464)Titanium dioxide (E171)Macrogol 400
Actavis UK Ltd
Actavis UK Ltd, a subsidiary of Accord Healthcare Ltd, Whiddon Valley, Barnstaple, Devon, EX32 8NS, UK
+44 (0)1271 346 106
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