Pharmacology: Pharmacokinetics: Absorption: Bioavailability: Rapidly and extensively absorbed following oral administration, with peak plasma concentration (Cmax) usually attained in 0.9 hr.
Onset: Antihistaminic effects occur within 1 hr. Symptomatic improvement observed as early as 1 day after initiation of therapy for allergic rhinitis or chronic idiopathic urticaria.
Duration: Antihistaminic effects persist for at least 24 hrs.
Food: A high-fat meal reduces Cmax by about 36% and delays time to peak plasma concentration (Tmax) by about 1.25 hrs, but does not affect the area under the concentration-time curve (AUC).
Special Populations: In patients with renal impairment, AUC is increased by 1.8-, 3.2- or 4.3-fold in those with mild, moderate or severe impairment, respectively; AUC is increased by 5.7-fold in those with end-stage renal disease. In pediatric patients, Cmax and AUC following administration of 5-mg dose is approximately twice than that in adults.
Distribution: Extent: Average apparent volume of distribution is 0.4 L/kg, which represents distribution in total body water. Expected to distribute into milk.
Plasma Protein-Binding: Approximately 91-92% (mainly albumin).
Elimination: Metabolism: Metabolized to a limited extent (<14% of dose) by aromatic oxidation, N-dealkylation, O-dealkylation and taurine conjugation.
Elimination Route: Excreted in urine (85.4%) (via glomerular filtration and active tubular secretion) and in feces (12.9%). Less than 10% of dose removed by standard 4-hr hemodialysis procedure.
Half-Life (t½): Approximately 8 hrs.
Special Populations: In patients with renal impairment, t½ is increased by 1.4-, 2- or 2.9-fold in those with mild, moderate or severe impairment, respectively; t½ is increased by 4-fold in those with end-stage renal disease. Total body clearance also progressively decreases based on severity or renal impairment (see Renal Impairment under Dosage & Administration).
In pediatric patients receiving a single 5-mg dose, total body clearance was 30% greater and elimination t½ is 24% shorter than those observed in adults. In geriatric patients receiving 30 mg once daily for 6 days, total body clearance was 30% lower than that observed in younger adults; however, levocetirizine disposition appears to be dependent on renal function rather than on age.
Treatment of allergic rhinitis and chronic idiopathic urticaria.
Children ≥12 years: 5 mg once daily; alternatively, 2.5 mg once daily may be adequate for some patients.
Elderly: Select dosage with caution (usually starting at low end of dosage range) because of age-related decreases in hepatic, renal and/or cardiac function, and concomitant disease and drug therapy. (See Use in the elderly under Precautions.)
Renal Impairment: The dose of levocetirizine hydrochloride should be reduced in patients with renal impairment according to creatinine clearance (CrCl), although recommendations can vary between countries. The following oral doses have been suggested for adults in the United Kingdom (UK) and for adults and adolescents ≥12 years in the United States of America (USA): CrCl 50-79 mL/min: 5 mg once daily in the UK; 2.5 mg once daily in the USA.
CrCl 30-49 mL/min: 5 mg every other day in the UK; 2.5 mg every other day in the USA.
CrCl 10-29 mL/min: 5 mg once every 3 days in the UK; 2.5 mg once every 3 or 4 days in the USA.
CrCl <10 mL/min and patients undergoing dialysis: contraindicated both in the UK and USA.
Data are lacking for the use of levocetirizine in children with renal impairment. The dose should be adjusted on an individual basis, taking into account the patient's renal clearance and body weight.
Administration: Administer orally once daily in the evening without regard to meals.
Hypersensitivity to levocetirizine or any of the excipients of Levocet-Natrapharm, or to cetirizine.
Adults and children ≥12 years with end-stage renal disease (CrCl <10 mL/min) or undergoing hemodialysis.
General: Central Nervous System (CNS) Effects: Somnolence, fatigue and asthenia reported. Caution required when performing hazardous activities requiring mental alertness or physical coordination (eg, operating machinery, driving a motor vehicle).
Specific Populations: Hepatic Impairment: Pharmacokinetics not evaluated, but clearance unlikely to be decreased. Dosage adjustment not necessary.
Renal Impairment: Decreased clearance, resulting in increased risk of adverse effects. Dosage adjustment necessary based on degree of renal impairment (see Dosage & Administration).
Use in pregnancy: No clinical data on exposed pregnancies are available. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/fetal development. Caution should be exercised when prescribing to pregnant or lactating women.
Use in lactation: Expected to distribute into milk (as cetirizine is distributed into milk). Use not recommended.
Use in children: Safety and efficacy not established in children <6 years. Efficacy of 2.5 mg dally dosage for management of allergic rhinitis or chronic idiopathic urticaria in children 6-11 years is based on extrapolation of demonstrated efficacy of 5 mg daily dosage in children ≥12 years and on pharmacokinetic comparisons in adults and children. Efficacy of 5 mg dally dosage for management of chronic idiopathic urticaria in children ≥12 years is based on extrapolation of demonstrated efficacy in adults.
Use in the elderly: Insufficient experience in patients ≥65 years to determine whether geriatric patients respond differently than younger adults. Select dosage with caution because of age-related decreases in hepatic, renal and/or cardiac function, and concomitant disease and drug therapy. (See Dosage & Administration.) Periodic monitoring of renal function may be useful.
Common Adverse Effects: Children 6-12 (with 5 mg Daily Dosage): Pyrexia, cough, somnolence, epistaxis.
Adults and Children ≥12 years: Somnolence, nasopharyngitis, fatigue, dry mouth, pharyngitis.
No formal drug interaction studies with levocetirizine to date; studies have been performed with racemic cetirizine. Does not inhibit cytochrome P-450 (CYP) isoenzymes 1A2, 2C9, 2C19, 2A1, 2D6, 2E1 or 3A4. Does not induce uridine diphosphate glucuronosyltransferase (UGT) 1A or CYP isoenzymes 1A2, 2C9 or 3A4. Unlikely to produce or be subject to pharmacokinetic interactions associated with metabolic enzyme systems.
Azithromycin: No clinically important changes in electrocardiogram (ECG) parameters observed following concomitant use with cetirizine and no clinically important interactions reported following such concomitant use.
Central Nervous System Depressants (eg, Alcohol): Possible additive CNS effects. Avoid concomitant use.
Cimetidine: No pharmacokinetic interactions observed with cetirizine.
Erythromycin: No clinically important changes in ECG parameters observed following concomitant use with cetirizine and no clinically important interactions reported following such concomitant use.
Ketoconazole: Prolongation of QTc interval (with an increase of 17.4 msec) observed following concomitant administration with cetirizine. No other clinically important interactions reported following such concomitant use. Not considered clinically important.
Pseudoephedrine: No pharmacokinetic interactions observed with cetirizine.
Ritonavir: Increased AUC (42%), increased t½ (53%) and decreased clearance (29%) of cetirizine; disposition of ritonavir did not altered following concomitant administration with cetirizine.
Theophylline: Decreased clearance (16%) of cetirizine; disposition of theophylline did not altered following concomitant administration with cetirizine.
Store at room temperatures not exceeding 30°C.
R06AE09 - levocetirizine ; Belongs to the class of piperazine derivatives used as systemic antihistamines.
Levocet-Natrapharm FC tab 5 mg
30's (P560.85/box)
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