Levocetirizine dihydrochloride.
Each film coated tablet contains levocetirizine dihydrochloride 5 mg.
Levocetirizine is a second generation antihistamine. The molecular formula of levocetirizine is C21H25ClN2O3 which similar to cetirizine. However, the chemical formula of them are different since levocetirizine is an active R-enantiomer of cetirizine racemate. The chemical formula of levocetirizine is [2-[4-(R)-p-Chloro-α-phenylbenzyl]-1-piperazinyl]ethoxy]acetic acid.
Pharmacology: Pharmacodynamics: Mechanism of Action: Levocetirizine, an active R-enantiomer of cetirizine, is a second generation antihistamine. The drug, as other antihistamines, is reversible, competitive H1 receptor antagonist. In in vitro binding studies, levocetirizine has a twofold higher affinity for H1 receptor than cetirizine. Levocetirizine at a half dosage of cetirizine appears to be as potent as cetirizine in histamine-induced allergic sneezing, increased airway resistance, and skin wheal and flare.
Pharmacokinetics:Absorption: Levocetirizine is rapidly and extensively absorbed following oral administration. Peak plasma concentration (Cmax) were observed at 0.9 hours and 0.5 hours after administration of levocetirizine tablets and oral solution, respectively. Coadministration of levocetirizine and high fat diet delays the absorption of levocetirizine by 1.25 hours and reduces the peak plasma concentration by approximately 36%. Area under the plasma concentration-time curve (AUC) of levocetirizine is not affected by food. Onset of action of levocetirizine occurs within 1 hour following administration on an empty stomach. Symptomatic improvement of allergic rhinitis or chronic urticaria were observed as early as 1 day after initiation of levocetirizine therapy.
Distribution: Levocetirizine distributes in total body water and expected to distribute into breast milk. The average apparent volume of distribution (Vd) of levocetirizine in human body is 0.4 L/kg and its protein binding is approximately 91-92%.
No tissue distribution data are available in humans, neither concerning the passage of levocetirizine through the blood-brain-barrier.
Metabolism and Elimination: A small amount of levocetirizine (less than 14% of administered dose) is metabolized by hepatic enzyme systems including aromatic oxidation, N-dealkylation, O-dealkylation, and taurine conjugation. 85.4% of the dose is excreted in urine via glomerular filtration and active tubular secretion. 12.9% of the dose is found in feces. The half-life (T1/2) of levocetirizine in healthy adult is approximately 8-9 hours. In patients with renal impairment, the elimination half-life is increased by 1.4-, 2-, 2.9-, or 4-fold in those with mild, moderate, severe impairment, or end-stage renal impairment, respectively.
Levocetirizine is indicated as a symptomatic treatment for allergic conditions including: Perennial and seasonal allergic rhinitis, chronic idiopathic urticaria.
General recommendation: Levocetirizine is given once daily. Age-based recommended daily doses of levocetirizine are as following: Adults and Children 12 years of age and older: 5 mg daily. A dosage of 2.5 mg once daily may be adequate for some patients.
Children 6-11 years of age: 2.5 mg daily.
Dosage Adjustment in Renal Impairment: The clearance of levocetirizine is decreased in patients with renal impairment and dosage adjustment in these patients is required. Dosage of levocetirizine in adults and children 12 years of age and older should be based on the degree of renal impairment as shown in following table. Use of levocetirizine is contraindicated in children younger than 12 years old with renal impairment. (See Table.)
Click on icon to see table/diagram/image
Dosage Adjustment in Hepatic Impairment: Dosage adjustment is not necessary in patients with hepatic impairment.
Administration: Levocetirizine is orally administered once daily in the evening without regard to meals. The tablets of levocetirizine is scored and can be divided in half. Each half provides 2.5 mg of levocetirizine.
No serious clinical symptoms has been reported due to overdosage of levocetirizine. Less than 10% of an administered dose of levocetirizine is removed during a standard 4-hours hemodialysis. There is no specific antidote for levocetirizine overdose. Therefore, symptomatic and supportive treatment should be administered as appropriate.
Levocetirizine should not be used in these groups of patients: Patients with known hypersensitivity to levocetirizine, cetirizine or any ingredients in the formulation; Adults and children 12 years of age and older with end-stage renal failure (creatinine clearance less than 10 ml/min) or undergoing dialysis; Children younger than 12 years of age with renal impairment.
Central nervous system (CNS) side effects including somnolence, fatigue, and asthenia have been reported in patients receiving levocetirizine. Patients taking levocetirizine should be advised to avoid activities requiring complete mental alertness or physical coordination. Concomitant use of levocetirizine with alcohol or other CNS depressants should be avoided.
Effects on Ability to Drive and Use Machines: Patients intending to drive, engaging in potentially hazardous activities or operating machinery should not exceed the recommended dose and should take their response to the medicinal product into account. In these sensitive patients, concurrent use with alcohol or other CNS depressants may cause additional reductions in alertness and impairment of performance.
Pregnancy category: B. Safety of levocetirizine in pregnant women has not been established in clinical data. Levocetirizine may be used in pregnant women with special precaution.
Levocetirizine is expected to be excreted in human milk, based on data of cetirizine racemate. Therefore, levocetirizine should be avoided in nursing women.
Levocetirizine is generally well tolerated. However, the following reported undesirable effects may be found.
Undesirable effects reported in 2% or more of patients 12 years of age and older include somnolence, nasopharyngitis, fatigue, dry mouth, and pharyngitis.
Undesirable effects reported in 2% or more of patients 6-12 years of age include pyrexia, cough, somnolence, and epistaxis.
Undesirable effects reported in 2% or more of patients 1-5 years of age include pyrexia, diarrhea, vomiting, and otitis media.
Undesirable effects reported in 3% or more of patients 6-11 months of age include diarrhea, and constipation.
Including to the adverse reactions reported during clinical studies and listed above, very rare cases of the following adverse drug reactions have been reported in post-marketing experience such as hypersensitivity including anaphylaxis, dyspnea, nausea, angioneurotic oedema, pruritis, rash, urticaria and weight increase.
Interactions among levocetirizine and other medications have not been completely studied. However, levocetirizine is unlikely to produce or be subject to pharmacokinetic drug interactions since the drug does not inhibit nor induce cytochrome P450 (CYP450) enzyme system and uridine diphosphate glucuronosyltransferase (UGT)1A.
Concomitant use with CNS Depressants: Concomitant use of levocetirizine with other CNS depressants including alcohol may potentiate CNS side effects of levocetirizine. Concomitant use should be avoided.
Concomitant use with CYP Inhibitors: No pharmacokinetic interactions were observed in patients receiving levocetirizine and CYP inhibitors including cimetidine and erythromycin. Prolongation of the QTc interval was reported in a small number of patients receiving cetirizine racemate and ketoconazole concomitantly. However, this interaction is not considered clinically important. There are reports of increased area under the plasma concentration-time curve (AUC) (42%), increased half life (53%), and decreased clearance (29%) of cetirizine racemate in patients receiving ritonavir.
Concomitant use with Other Medications: No data indicates possible interaction of levocetirizine and theophylline. However, concomitant use of cetirizine racemate with theophylline decreases clearance of cetirizine by 16%.
Store below 30°c in a dry place, away from direct sunlight.
R06AE09 - levocetirizine ; Belongs to the class of piperazine derivatives used as systemic antihistamines.
Zyller FC tab 5 mg
10 × 10's
Sign Out
Click on icon to see table/diagram/image
