Each film coated tablets contains;
Levocetirizine Dihydrochloride 5mg
For excipients, see section 6.1

Therapeutic indications
– Seasonal allergic rhinitis, hay fever (pollinosis);
– Chronic allergic rhinitis, provoked by pets, dust, cold and other factors;
– Allergic conjunctivitis;
– Allergic dermatitis, eczema, urticaria, including chronic idiopathic urticaria, atopic dermatitis, angioedema; – Along with the drugs having a high risk of allergization (antibiotics, vaccines, sera).

Posology and method of administration
The medicine is administered orally without chewing with some water. The medicine effect is more rapid if used on empty stomach. The recommended dose for adults is 5 mg (1 tablet 1 time per day). The course of the treatment of hay fever (pollinosis) is from 1 to 6 weeks. In chronic allergic diseases the course of treatment can continue up to 18 months.
Elderly:
Adjustment of the dose is recommended in elderly patients with moderate to severe renal impairment (see Patients with renal impairment below).

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:

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 his body weight. There are no specific data for children with renal impairment.

Patients with hepatic impairment:
No dose adjustment is needed in patients with solely hepatic impairment. In patients with hepatic impairment and renal impairment, adjustment of the dose is recommended (see Patients with renal impairment above).
Duration of use:
Intermittent allergic rhinitis (symptoms <4days/week or during less than 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 >4days/week and during more than 4 weeks), continuous therapy can be proposed to the patient during the period of exposure to allergens. Clinical experience with 5 mg levocetirizine as a film-coated 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.

Effects on ability to drive and use machines
Taking into consideration the possibility of side effects development (drowse, fatigability, asthenia) ability to drive and operate other machines must conduct a doctor after studying an individual patient’s reaction to the medicine.

Undesirable effects
Central nervous system:
headache, drowse, fatiguability, weakness.
Cardio-vascular system:
palpitation sensation.
Visual organ:
visual impairment.
Hepatobiliary system:
hepatitis.
Immune system:
hypersensitivity, including anaphylaxis and angioneurotic edema.
Respiratory system:
short breath.
Digestive system:
dry mouth, nausea.
Skin and subcutaneous tissue:
skin itch, rash and urticaria.
Others:
body weight enlargement; gastric pain; mialgia; liver function test can be increased.

Interaction with other medicinal products and other forms of interaction
The synchronous usage of the medicine with theophylline reduces the total Levocetirizine clearance. In trials of the concomitant usage of Levocetirizine with Ketoconazole and macrolides there were not any valid changes of cardiac function in electrocardiograms. In a case of the synchronous usage of Levocetirizine with central nervous system depressive medicines (tranquilizers, tricyclic antidepressants, MAO inhibitors) and alcohol it may cause drowsiness.
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.

Special warnings and precautions for use
Not recommended to use more than recommended dose.
Because of the medicine mainly elimination via kidneys it is necessary to administrate L-CET® carefully for patients with renal pathology.
In patients with the renal insufficiency (creatinine clearance < 40 ml/min) the Levocetirizine elimination is reduced (up to 80% in hemodialysis patients).
In renal insufficiency the therapeutic dose depends on creatinine clearance (CC). If CC is 50–80 ml/min and more the administration is 1 tablet per a day, if CC is 30–49 ml/min – 1 tablet every other day, if CC is 30 ml/min – 1 tablet every three days. If value of CC is less than 10 ml/min it is contraindicated. In hepatic insufficiency dose changes is not needed.

Pregnancy and lactation
For levocetirizine 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, parturition or postnatal development. Caution should be exercised when prescribing to pregnant or lactating women.

Effects on ability to drive and use machines
Taking into consideration the possibility of side effects development (drowse, fatigability, asthenia) ability to drive and operate other machines must conduct a doctor after studying an individual patient’s reaction to the medicine.

Overdose
Symptoms:
drowsiness, headache, dry mouth, nausea and epigastric pain.
In some cases:
blood stain in phlegm and bleeding.
Treatment:
removing the medicine from gastro-intestinal tract via gastric lavage and administration of sorbents with further symptomatic therapy. Less than 10% of Levocetirizine is removed via hemodialysis.

Contraindications
-Hypersensitivity to Levocetirizine or other drug components;
-Pregnancy and lactation;
-Children age less than 18 years.

PHARMACEUTICAL FORM
Film coated tablet
Green colored, round, biconvex film-coated tablets.

PHARMACOLOGICAL PROPERTIES
Pharmacotherapeutic Group:
antihistamine for systemic use, piperazine derivative
ATC Code   :     R06AE09

Pharmacodynamic properties
Pharmacotherapeutic group: Antihistamine for systemic use, piperazine derivatives, Levocetirizine, the (R) enantiomer of cetirizine, is a potent and selective antagonist of peripheral H1-receptors. Levocetirizine is rapidly absorbed after oral administration; the simultaneous use of meal decreases the absorption rate but does not affect over its completeness. After single dose intake the drug effect begins after 15 minutes and lasts for 24 hours.
Levocetirizine bioavailability is 100%. The concentration peak is 207ng/ml, TCmax – 0.9 hours, distribution volume – 0.4 l/kg. The binding with plasma proteins is 90%. The half-life period is 7–10 hours. More than 85% of the drug gets eliminated via kidneys. Levocetirizine is excreted in the breast milk.
Pharmacokinetic properties
Levocetirizine is H1-histamine receptors blocker, Cetirizine enantiomer and competitive antagonist of Histamine. Levocetirizine influences on a histamine dependent stage of allergic reactions, reduces the vessels penetrability and eosinophil migration, limits the release of inflammatory mediators and in this way prevents the allergic reactions development and significantly relieves their course, removes the exudation and itch. Levocetirizine has almost no anticholinergic and antiserotonin action. It does not pass through hematoencephalic barrier. Levocetirizine has almost no sedative effect if therapeutic doses used.
After oral administration of single dose the medication effect begins after 15 minutes and continues for 24 hours.

Absorption:
Levocetirizine is rapidly and extensively absorbed following oral administration. 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 levocetirizine through the blood-brain-barrier. In rats and dogs, the highest tissue levels are found in liver and kidneys, the lowest in the CNS compartment.
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 mean apparent total body clearance 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 feces 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, genotoxicity, carcinogenic potential, toxicity to reproduction.

PHARMACEUTICAL PARTICULARS
List of excipients
Microcrystalline cellulose (PH 102), Croscarmellose sodium, Colloidal silicon dioxide, Magnesium stearate, Opadry II 85 G 51300 green & Purified water

Incompatibilities Not applicable

Shelf life
3 years

Special precautions for storage
Store below 30°C. Keep out of reach of children.

Nature and contents of container 10 tablets are packed in an Alu/Alu blister pack and such 10 blisters are packed in a carton along with pack insert.

MARKETING AUTHORISATION HOLDER
Kusum Healthcare Private Limited
D-158 A, Okhla Industrial Area,
Phase I, New Delhi-110020,
India
MARKETING AUTHORISATION NUMBER(S)
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MANUFACTURER NAME
Kusum Healthcare Pvt. Ltd.
SP 289 (A), RIICO Indl. Area Chopanki, Bhiwadi (Rajasthan), INDIA
Telephone: +91-1493-516560/61/63
Telefax: +91-1493-516562
DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
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DATE OF REVISION OF THE TEXT
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