Zyphrine

Levocetirizine hydrochloride.

Each 5 mL solution contains: Levocetirizine hydrochloride 2.5 mg.

Pharmacology: Pharmacodynamics: Mechanism of action: Levocetirizine, the enantiomer of cetirizine, is a potent and selective antagonist of peripheral H1-receprtor. Levocetirizine competes with histamine for bindings at H1-receptor sites on the effect or cell surface, resulting in suppression of histaminic edema, flare, and pruritus. The low incidence of sedation can be attributed to reduce penetration of cetirizine into the CNS as a result lipophilic carboxyl group on the ethylamine side chain.
Pharmacokinetics: The pharmacokinetics of levocetirizine are linear with dose- and time-dependent with intersubject variability. The pharmacokinetic profile is the same when given as the single enantiomer or when given as cetirizine. No chiral inversion occurs during the process of absorption and elimination.
Absorption: Levocetirizine is rapidly and extensively absorbed following oral administration. In adults, peak plasma concentrations (C_max) are achieved 0.9 hr after dosing. Steady state is achieved after 2 days. Peak concentrations are typically 270 ng/mL and 308 ng/mL following a single and a repeated 5 mg once daily 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 blood-brain barrier. In rats and dogs, the highest tissue levels are found in liver and kidneys, the lowest in the central nervous system (CNS) compartment. In humans, levocetirizine is 90% bound to plasma proteins. The distribution of levocetirizine is restrictive, as the volume of distribution is 0.4 L/kg.
Metabolism: The extent of metabolism of levocetirizine in humans is <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 CYP3A4 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.
Elimination: The plasma t½ in adults is 7.9 ± 1.9 hrs. The mean apparent total body clearance in adults is 0.63 mL/min/kg. The major route of excretion of levocetirizine and metabolites is via urine, accounting for the 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.

Levocetirizine is indicated for: The relief of nasal and ocular symptoms of seasonal and perennial allergic rhinitis.
The relief of symptoms of chronic idiopathic urticaria.

Adults and Children 12 years of Age and Older: The recommended dose is 2 teaspoon (10 mL) oral once daily in the evening. Some patients may be adequately controlled by 1 teaspoon (5 mL) oral solution once daily in the evening.
Children 6 to 11 Years of Age: The recommended dose is 1 teaspoon (5 mL) once daily in the evening. The 2.5 mg should not be exceeded because the systemic exposure with 5 mg is approximately twice that of adults.
Children 6 months to 5 Years of Age: The recommended dose is 1.25 mg (½ teaspoon oral solution) [2.5 mL] once daily in the evening. The 1.25 mg once daily should not be exceeded based on comparable exposure to adults receiving 5 mg.
Elderly with Renal Impairment: Adjustment of the dose is recommended in elderly patients with moderate to severe renal impairment (see Renal Impairment as follows)
Renal Impairment: The dosing intervals must be individualized according to renal function. Refer to the table as follows and adjust the dose as indicated. To use dosing table an estimate of the patients CrCl in mL/min is needed. (See table.) The CrCl (mL/min) may be estimated from serum creatinine (mg/dL) determined using the following formula: See equation.

Click on icon to see table/diagram/image

Dosing adjustment for Patients with Impaired Renal Function: See table.

Click on icon to see table/diagram/image

In pediatric 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 and their body weight. There are no specific data for children with renal impairment.
Hepatic Impairment: No dose adjustment is needed in patients with solely hepatic impairment. In patients with hepatic and renal impairment, adjustment of the dose is recommended (see Renal Impairment as previously mentioned).
Duration of Use: Intermittent allergic rhinitis (symptoms <4 days/week or during <4 weeks) has to be treated according to the disease and its history; it can be stopped once the symptoms have disappeared and can be restarted again when symptoms reappear. In case of persistent allergic rhinitis (symptoms >4 days/week and during >4 weeks), continuous therapy can be proposed to the patient during the period of exposure to allergens.

Symptoms: Symptoms of overdose may include drowsiness in adults and initially agitation and restlessness, followed by drowsiness in children.
Treatments: There is no known specific antidote to Levocetirizine. Should overdose occur, symptomatic or supportive treatment is recommended. Gastric lavage should be considered following short-term ingestion. Levocetirizine is not effectively removed by haemodialysis.

Hypersensitivity to Levocetirizine, to the other piperazine derivatives, or to any of the excipients. Patients with severe renal impairment at less than 10 mL/min creatinine clearance. Patients problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine. Pediatric patients (children 6 months to 11 years of age) with impaired renal function.

The administration of Levocetirizine to infants and toddlers aged less than 2 years is not recommended.
Precaution is recommended with intake of alcohol.
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. Caution in epileptic patients and patients at risk of convulsions are recommended.
Patients should be cautioned against engaging hazardous occupations requiring complete mental awareness, and motor coordination such as operating machinery or driving a motor vehicle after ingestion of Levocetirizine hydrochloride. Concurrent use with alcohol or other CNS depressants should be avoided. Levocetirizine hydrochloride should be used with caution in patients with predisposing factors of urinary retention (e.g. spinal cord lesion, prostatic hyperplasia) as drug may increase the risk of urinary retention. Discontinue product if urinary retention occurs.

For Levocetirizine no clinical data on exposed pregnancies are available. Caution should be exercised when prescribing to pregnant or lactating women.

Headache, Somnolence, Mouth dryness, Fatigue, Hypersensitivity including anaphylaxis, aggression, agitation, convulsion, visual disturbances, palpitation, dyspnoea, nausea, hepatitis, angioneurotic oedema, fixed drug eruption, pruritus, rash and urticaria.

A small decrease in the clearance of cetirizine (16%) was observed in a multiple dose study with theophylline (400 mg once a day) in sensitive patients the simultaneous administration of cetirizine or Levocetirizine and alcohol or other CNS depressants may have effects on the central nervous system.

Store at temperatures not exceeding 30°C.

Antihistamines & Antiallergics

R06AE09 - levocetirizine ; Belongs to the class of piperazine derivatives used as systemic antihistamines.

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