Vietnam Product

lcet Tablets

lcet Tablets

Why you have been prescribed this medicine?

You have been prescribed this medicine if you have any of the following:

Symptomatic treatment of allergic rhinitis (including persistent allergic rhinitis) and urticaria.

When you should consult your doctor?

You should consult your doctor if you experience any of the following:

"Inform doctors about unexpected reactions after using drug."

What to do if you miss a dose?

If it is almost time for your next dose, skip the dose you missed and take your next dose when you are meant to.
Otherwise take it as soon as you remember and then go back to taking it as you would normally.

Things you MUST NOT DO while on this medicine?

Hypersensitivity to levocetirizine, to other piperazine derivatives, or to any of the excipients.
Patients with severe renal impairment at less than 10 ml/min creatinine clearance.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or
glucose-galactose malabsorption should not take this medicine.

What to do if you accidentally take too much (overdose) of the medicine?

a) Symptoms
Symptoms of overdose may include drowsiness in adults and initially agitation and restlessness, followed by drowsiness in children.

b) 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 short-term ingestion. Levocetirizine is not effectively removed by haemodialysis.

Is it safe in pregnancy and breast-feeding?

Tell your doctor immediately if you become pregnant while taking this medication.
For safety of any drug during pregnancy or breastfeeding – please consult your doctor.

Storage Conditions:

Storage
Store below 30°C.

Shelf life
2 years

Packing
Levocetrizine dihydrochloride film coated tablets are supplied in PVC/PVDC Blister pack of 10's and 3 such blisters (3 x 10 Tablets) are packed in a carton along with pack insert.
Manufacturer
Kusum Healthcare Private Limited Address SP 289 (A), RIICO Industrial Area, Chopanki, Bhiwadi, India

Drug Description

Composition:
Each film-coated tablet contains 5 mg of Levocetirizine Dihydrochloride.

Additional ingredients:
Microcrystalline cellulose, Croscarmellose sodium,Colloidal
anhydrous silica, Magnesium Stearate, Purified water.

Tablet coating:
Opadry II 85G51300 Green

Indications and dosage.

Indications:
Symptomatic treatment of allergic rhinitis (including persistent allergic rhinitis) and urticaria.
Administration & Dosage:
The film-coated tablet must be taken orally, swallowed whole with liquid and may be taken with or without food. It is recommended to take the daily dose in one single intake.

Adults and adolescents 12 years and above:
The daily recommended dose is 5 mg (1 film-coated tablet).

Elderly:
Adjustment of the dose is recommended in elderly patients with moderate to severe renal impairment (see Patients with renal impairment below).

Children aged 6 to 12 years:
The daily recommended dose is 5 mg (1 film-coated tablet).
For children aged 2 to 6 years no adjusted dosage is possible with the film-coated tablet formulation. It is recommended to use a paediatric formulation of levocetirizine.

Patients with renal impairment:
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 Patients with Impaired Renal Function:
Group Creatinine clearance (ml/min) Dosage and frequency


table

table Further uncommon incidences of adverse reactions (uncommon >1/1000, <1/100) like asthenia or abdominal pain were observed.
The incidence of sedating adverse drug reactions such as somnolence, fatigue, and asthenia was altogether more common (8.1 %) under levocetirizine 5 mg than under placebo (3.1%). In addition 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.
> Immune system disorders:
Hypersensitivity including anaphylaxis

> Psychiatric disorders:
Aggression, agitation

> Nervous system disorders:
Convulsion

> Eyes disorders:
Visual disturbances
> Cardiac disorders:
Palpitations

> Respiratory, thoracic, and mediastinal disorders:
Dyspnoea

> Gastrointestinal disorders:
Nausea

> Hepatobiliary disorders:
Hepatitis

> Skin and subcutaneous tissue disorders:
Angioneurotic oedema, fixed drug eruption, pruritus, rash, urticaria

> Musculoskeletal, connective tissues, and bone disorders:
Myalgia

> Investigations:
Weight increased, abnormal liver function tests

Side effects and drug interactions.

Adverse Drug Reaction
"Inform doctors about unexpected reactions after using drug."

Drug Interactions: No interaction studies have been performed with levocetirizine (including no studies with CYP3A4 inducers); studies with the racemate compound cetirizine demonstrated that there were no clinically relevant adverse interactions (with pseudoephedrine, cimetidine, ketoconazole, erythromycin, azithromycin, glipizide and diazepam). A small decrease in the clearance of cetirizine (16%) was observed in a multiple dose study with theophylline (400) mg once a day); while the disposition of theophylline was not altered by concomitant cetirizine administration.
The extent of absorption of levocetirizine is not reduced with food, although the rate of absorption is decreased.
In sensitive patients the simultaneous administration of cetirizine or levocetirizine and alcohol or other CNS depressants may have effects on the central nervous system, although it has been shown that the racemate cetirizine does not potentiate the effect of alcohol. Drug interaction studies have been performed with racemic cetirizine.
Antipyrine, Azithromycin, Cimetidine, Erythromycin, Ketoconazole, Theophylline,and Pseudoephedrine: Pharmacokinetic interaction studies performed with racemic cetirizine demonstrated that cetirizine did not interact with antipyrine, pseudoephedrine, erythromycin, azithromycin, ketoconazole, and cimetidine. There was a small decrease (~16%) in the clearance of cetirizine caused by a 400 mg dose of theophylline. It is possible that higher theophylline doses could have a greater effect.

Pseudoephedrine:
Pharmacokinetic interaction studies performed with racemic cetirizine demonstrated that cetirizine did not interact with antipyrine, pseudoephedrine, erythromycin, azithromycin, ketoconazole, and cimetidine. There was a small decrease (~16%) in the clearance of cetirizine caused by a 400 mg dose of theophylline. It is possible that higher theophylline doses could have a greater effect.

Warnings and precautions

Precautions in use:
The use of the film-coated tablet formulation is not recommended in children aged less than 6 years since this formulation does not allow for appropriate dose adaptation. It is recommended to use a paediatric formulation of levocetirizine.
The administration of levocetirizine to infants and toddlers aged less than 2 years is not recommended. Precaution is recommended with intake of alcohol.

Overdosage and Contraindications

Contraindication:
Hypersensitivity to levocetirizine, to other piperazine derivatives, or to any of the excipients. Patients with severe renal impairment at less than 10 ml/min creatinine clearance. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Overdosage:
a) Symptoms
Symptoms of overdose may include drowsiness in adults and initially agitation and restlessness, followed by drowsiness in children.

b) 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 short-term ingestion. Levocetirizine is not effectively removed by haemodialysis.

Clinical pharmacology.

Pharmaceutical Form: Film-coated tablet.
Pharmacotherapeutic group: Antihistamine for systemic use.
Pharmacological properties:
Pharmacodynamic: Levocetirizine, the (R) enantiomer of cetirizine, is a potent and selective antagonist of peripheral H1-receptors.
Binding studies revealed that levocetirizine has high affinity for human H1-receptors (Ki = 3.2 nmol/l). Levocetirizine has an affinity 2-fold higher than that of cetirizine (Ki = 6.3 nmol/l). Levocetirizine dissociates from H1-receptors with a half-life of 115 ± 38 min. Pharmacodynamic studies in healthy volunteers demonstrate that, at half the dose, levocetirizine has comparable activity to cetirizine, both in the skin and in the nose. In vitro studies (Boyden chambers and cell layers techniques) show that levocetirizine inhibits eotaxin-induced eosinophil transendothelial migration through both dermal and lung cells. A pharmacodynamic experimental study in vivo (skin chamber technique) showed three main inhibitory effects of levocetirizine 5 mg in the first 6 hours of pollen-induced reaction, compared with placebo in 14 adult patients: inhibition of VCAM-1 release, modulation of vascular permeability and a decrease in eosinophil recruitment. The efficacy and safety of levocetirizine have been demonstrated in several double-blind, placebo controlled, clinical trials performed in patients suffering from seasonal allergic rhinitis or perennial allergic rhinitis. Clinical experience with 5 mg levocetirizine as a - tablet formulation is currently available for a 6-month treatment period. For chronic urticaria and chronic allergic rhinitis, up to one year's clinical experience is available for the racemate, and up to 18 months in patients with pruritus associated with atopic dermatitis. A 6-month clinical study in 551 patients (incl. 276 levocetirizine-treated patients) suffering from PAR (symptoms present 4 days a week for at least 4 consecutive weeks) and sensitized to house dust mites and grass pollen demonstrated that levocetirizine 5 mg was clinically and statistically significantly more potent than placebo on the relief from the total symptom score of allergic rhinitis throughout the whole duration of the study, without any tachyphylaxis. During the whole dura
Pharmacokinetic / pharmacodynamic relationship: 5 mg levocetirizine provide a similar pattern of inhibition of histamine-induced wheal and flare than 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

Pharmacokinetic properties:
Mechanism of Action: Levocetirizine, the active enantiomer of cetirizine, is an antihistamine; its principal effects are mediated via inhibition of H1 receptors. The antihistaminic activity of levocetirizine has been documented in a variety of animal and human models. In vitro binding studies revealed that levocetirizine has an affinity for the human H1-receptor 2- fold higher than that of cetirizine (Ki = 3 nmol/L vs. 6 nmol/L, respectively. The clinical relevance of this finding is unknown.
The pharmacokinetics of levocetirizine are linear with dose- and time-independent with low inter-subject 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 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 the blood-brain-barrier. In rats and dogs, the highest tissue levels are found in liver and kidneys, the lowest in the 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.

Biotransformation:
The 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.

Elimination:
The plasma half-life in adults is 7.9 ± 1.9 hours. The half-life is shorter in small children.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 a mean of 85.4% of the dose. Excretion via faeces accounts for only 12.9% of the dose. Levocetirizine is excreted both by glomerular filtration and active tubular secretion.

Renal impairment:
The 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. The amount of levocetirizine removed during a standard 4-hour hemodialysis procedure was < 10%.

Preclinical safety data:
Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, toxicity to reproduction, genotoxicity or carcinogenicity.

Storage
Store below 30°C.

Shelf life
2 years

Packing
Levocetrizine dihydrochloride film coated tablets are supplied in PVC/PVDC Blister pack of 10's and 3 such blisters (3 x 10 Tablets) are packed in a carton along with pack insert. Manufacturer
Kusum Healthcare Private Limited Address SP 289 (A), RIICO Industrial Area, Chopanki, Bhiwadi, India

CERTIFICATES

KEEP IN TOUCH

Kusum Healthcare Pvt Ltd

Regd. Office: D-158A, Okhla Industrial Area

Phase-1, New Delhi-110020, India

Tel: 011-41005147, 40514919

Fax: +91-11-40527575

Email: kusumhealth@kusumhealthcare.com

CIN: U65929DL1997PTC085780