INSERT TEXT UAP Levocetirizine dihydrochloride Allerzet 5 mg Tablet Antihistamine FORMULATION Each film-coated tablet contains: Levocetirizine dihydrochloride.. 5 mg PRODUCT DESCRIPTION Levocetirine 5 mg (Allerzet) is a white, round, biconvex, film-coated tablet that is plain on both sides. PHARMACODYNAMICS Levocetirizine is a selective H 1 antagonist that is an active R-enantiomer of cetirizine, a second generation antihistamine. Studies have shown that levocetirizine has twice the H 1 receptor affinity of cetirizine. Levocetirizine (at half of cetirizine dosage) appears to be as potent as cetirizine in inhibiting histamine-induced sneezing, nasal airway resistance and skin wheal and flare. Compared with other antihistamines (e.g., desloratadine, fexofenadine, loratadine), it exhibits greater and more consistent inhibition of histamine-induced wheal and flare; it has a more rapid onset and longer duration of action than other antihistamines. 1 of 6
PHARMACOKINETICS Levocetirizine is rapidly and extensively absorbed after oral administration. Peak plasma concentrations (C max ) (270 ng/ml and 308 ng/ml for single and repeated 5 mg doses, respectively) are seen at 0.9 hour following oral administration in adults. Levocetirizine can be taken with or without food. In vitro, mean plasma protein binding of levocetirizine is from 91 to 92%. The average apparent volume of distribution is approximately 0.4 L/kg. In humans, the extent of levocetirizine metabolism is less than 14% of the dose. Metabolic pathways include aromatic oxidation, N- and O-dealkylation and taurine conjugation. Levocetirizine is excreted mainly by the kidneys and the plasma half-life is about 8 to 9 hours following oral administration. Levocetirizine is excreted in the urine both by glomerular filtration and active tubular secretion. Mean oral total body clearance is approximately 0.63 ml/kg/min. Clearance of levocetirizine may not be significantly decreased in patients with solely hepatic impairment since levocetirizine is mainly excreted unchanged by the kidneys. Dosage adjustment is necessary for mild to severe renal impairment. INDICATIONS This medicine is used for: Allergic rhinitis: Symptomatic relief of seasonal (e.g., hay fever) and perennial allergic rhinitis Chronic idiopathic urticaria: Symptomatic treatment of uncomplicated skin manifestations DOSAGE AND ADMINISTRATION Adults and Children 12 years and older... Orally, 1 tablet once a day, at bedtime, Or, as recommended by a physician. Use in Elderly Dose should be carefully selected, usually starting at the lowest dose. 2 of 6
Hepatic and Renal Impairment No dosage adjustment is necessary for patients with solely hepatic impairment. For renal impairment in adults and children > 12 years old, proper dosage adjustment should be done according to the degree of renal impairment. Dosage for Symptomatic Treatment of Allergic Rhinitis and Chronic Idiopathic Urticaria in Adults and Children > 12 Years Old with Renal Impairment Degree of Renal Impairment Creatinine Clearance (ml/min) Oral Levocetirizine Dose Mild 50 to 79 1 tablet once a day Moderate 30 to 49 1 tablet once every 2 days Severe < 30 1 tablet once every 3 days End-Stage Renal Disease; Patients Undergoing Dialysis < 10 CONTRAINDICATED CONTRAINDICATIONS Hypersensitivity to levocetirizine, cetirizine, other piperazine derivatives, or any component of the product Adults and children > 12 years old with end-stage renal disease (creatinine clearance < 10 ml/min) or undergoing hemodialysis Pediatric patients 6 to 11 years of age with renal impairment Patients who are pregnant or breastfeeding WARNINGS AND PRECAUTIONS Somnolence, fatigue and asthenia are associated with levocetirizine treatment. Patients should exercise caution when performing hazardous activities requiring mental alertness and physical coordination (e.g., driving, operating machinery). Caution should be observed in epileptic patients and patients at risk of convulsions for possible increased risk of adverse effects. 3 of 6
INTERACTIONS WITH OTHER MEDICAMENTS CNS Depressants (e.g., Alcohol): Avoid concomitant use as a possible additive effect may be evident. Ritonavir: Ritonavir disposition is not altered but this may cause increased plasma AUC (42%), increased half-life (53%) and decreased clearance (29%) of cetirizine. Theophylline: Theophylline disposition is not altered but studies show that 400 mg theophylline decreased the clearance (~16%) of cetirizine. Higher doses may have a greater effect. Ketoconazole: Concomitant administration with cetirizine caused prolongation of QT C interval (increase of 17.4 msec). This was not considered clinically important. Azithromycin, Erythromycin, Cimetidine, Pseudoephedrine: No clinically important changes in ECG parameters and no pharmacokinetic interactions were observed with cetirizine. STATEMENT ON USAGE FOR HIGH RISK GROUPS Pregnancy: Pregnancy Category B. No adequate and well-controlled studies in pregnant women are available for levocetirizine. Levocetirizine should only be used during pregnancy when clearly needed. Lactation: The use of levocetirizine is not recommended in breastfeeding women as it is possibly distributed into milk (cetirizine is distributed into milk). Use in the elderly: Clinical experience with levocetirizine has not identified differences in responses between the elderly and younger patients. However, dose should be carefully selected for elderly patients, usually starting at the lowest dose due to greater frequency of decreased hepatic, renal or cardiac function and of concomitant disease or other drug therapy. Renal Impairment: Levocetirizine is mainly excreted by the kidneys and the risk of adverse effects may be greater in patients with impaired renal function. 4 of 6
UNDESIRABLE EFFECTS Common (above 1%) Adults and Children > 12 years old: Somnolence, headache, fatigue, dry mouth, nasopharyngitis, and pharyngitis Children 6 to 11 years old: Pyrexia, somnolence, cough, epistaxis, and rhinitis Uncommon (0.1 to 1%) to Very Rare (< 0.01%) General: Asthenia, malaise, edema, hypersensitivity, and anaphylactic shock Neurologic: Agitation, paresthesia, aggression, confusion, depression, hallucination, insomnia, convulsions, movement disorders, tic, dysgeusia, syncope, tremor, dystonia, and dyskinesia Dermatologic: Pruritus, rash, urticaria, angioneurotic edema, and fixed drug eruption Gastrointestinal: Abdominal pain and diarrhea Hepatobiliary: Increased transaminases, alkaline phosphatase, gamma-glutamyl transpeptidase (GGT), and bilirubin Ophthalmic: Accomodation disorder, blurred vision and oculogyration Genitourinary: Dysuria and enuresis Others: Tachycardia, thrombocytopenia and increased weight OVERDOSE AND TREATMENT Symptoms of levocetirizine overdosage in adults may include drowsiness. In children, symptoms are initially agitation and restlessness, followed by drowsiness. No specific antidote is known and overdose is addressed by symptomatic or supportive treatment. Following short-term ingestion, gastric lavage may be considered. Dialysis may be ineffective unless a dialyzable agent was concomitantly ingested. STORAGE CONDITION Keep the product out of reach and sight of children Store at temperatures not exceeding 30 C 5 of 6
AVAILABILITY NAME / LOGO OF MANUFACTURER / IMPORTER / MARKETING AUTHORIZATION HOLDER CAUTION Foods, Drugs, Devices, and Cosmetics Act prohibits dispensing without prescription. DATE OF REVISION OF PACKAGE INSERT Note to UAP: Package insert revision date should be the date when the package insert is approved by Food and Drug Administration (FDA). 6 of 6