Unimed Levocetirizine

Levocetirizine dihydrochloride.

Tablet: Each film coated tablet contains: Levocetirizine Dihydrochloride 5mg, Titanium dioxide and Quinoline yellow as colouring agents.
Syrup: Each 5ml contains: Levocetirizine dihydrochloride 2.5mg and sunset yellow as permitted colour.
Orange coloured syrup pleasantly flavoured having a sweet taste and no sediment filled in amber colour bottle, sealed with ROPP cap labeled and placed in a printed carton.

Pharmacology: Pharmacodynamics: Levocetirizine is the active component of Cetirizine. It is a selective competitive inhibitor for the H1-histamine receptor, both in vitro and in vivo. There is no evidence of any binding with other receptors at concentrations 500 fold higher than those displacing a H1-ligand. It is effective in antagonizing histamine effects in both cutaneous and pulmonary models after IV and PO administration of 0.1-0.2 mg/kg. As with cetirizine safety pharmacology studies indicate a high margin of safety for adverse effects on the CNS, GI, immune and cardiovascular systems. Levocetirizine is unlikely to be involved in torsades de pointes or other arrhythmias. In addition, as levocetirizine is mainly excreted unchanged in man and does not inhibit the major CYP isoforms in human liver microsomes, cardiac and other adverse effects due to pharmacokinetic interactions are also unlikely.
Pharmacokinetics: The pharmacokinetic profile of levocetirizine is linear and time-independent with low inter-subject variability. The clearance of levocetirizine differs slightly in men and women. This difference is clearance, however, does not necessitate the use of a different dose or different dosage intervals in men and women. The pharmacokinetic profiles 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. Peak plasma concentrations are achieved 0.9 h after dosing. Steady state is achieved after two days. Peak concentrations are typically 270ng/ml and 308ng/ml following a single and 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. Levocetirizine is 90% bound to plasma proteins. The distribution of Levocetirizine is restrictive, as the volume of distribution is 0.41 /kg.
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 is via urine, accounting for a mean of 85.4% of the dose. Excretion via faeces accounts for only 12.9% of the dose. The renal clearance of levocetirizine is close to 30 ml /min/ 1.73m². When corrected for protein binding the value is about 260ml/min/1.73 m². Therefore, 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%.

Levocetirizine is indicated for the symptomatic treatment of allergic rhinitis (including persistent allergic rhinitis) and chronic idiopathic urticaria.

Tablet: 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 in recommended in elderly patients with compromised renal function (see patients with renal impairment as follows).
Children aged 6 to 12 years: The daily recommended dose is 5 mg (1 film-coated tablet). For children aged less than 6 years no adjusted dosage is yet possible.
Solution: Instruction for use: Appropriate volume of oral solution should be measured with oral syringe, and poured in a spoon or in a glass of water. The oral solution must be taken orally immediately after dilution, and may be taken with or without food.
Adults and adolescents 12 years and above: The daily recommended dose is 5 mg (10 ml of solution).
Elderly: Adjustment of the dose is recommended in elderly patients with moderate to severe renal impairment (see Patients with renal impairment as follows).
Children aged 6 to 12 years: The daily recommended dose is 5 mg (10 ml of solution).
Children aged 2 to 6 years: The daily recommended dose is 2.5 mg to be administered in 2 takes of 1.25 mg (2.5 ml of solution twice daily).
Due to the lack of data in this population, the administration of the product to infants and toddlers aged less than 2 years is not recommended.
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 patients creatinine clearance (CLcr) in ml/min is needed. The CLcr (ml/min) may be estimated from serum creatinine (mg/dl) determination using the following: (See equation.)

Click on icon to see table/diagram/image

Dosing adjustments for patients with impaired renal function: (See table.)

Click on icon to see table/diagram/image

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 as previously mentioned).
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 >4 days/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, clinical experience is available for the racemate.
Mode of administration: Oral.

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

History of hypersensitivity to levocetirizine or any of the other constituents of the formulation or to any piperzine derivatives. Patients with severe renal impairment at less than 10 ml/min creatinine clearance.

The use of LEVOCETIRIZINE TABLETS 5MG is not recommended in children aged less than 6 years since the currently available film-coated tablets do not yet allow dose adaption. Precaution is recommended with intake of alcohol (see Interactions). Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Effects on ability to drive and use machines: Comparative clinical trials have revealed no evidence that cetirizine, the racemate of levocetirizine, impairs mental alertness, reactivity or the ability to drive. This also applies to the use of this drug in the recommended dosage. Nevertheless, patients intending to drive, engage in potentially hazardous activities or operate machinery should not exceed the recommended dose and should take their response to the medicinal product into account. In those sensitive patients, concurrent use with alcohol or other CNS depressants may cause additional reductions in alertness and impairment of performance.

For Levocetirizine no clinical data an 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.

From clinical studies, mainly mild to moderate side effects such as dry mouth, headache, fatigue and somnolence have been reported commonly (above 1%). Further uncommon incidences of adverse reactions like asthenia or abdominal pain were observed. In addition to the adverse reported during clinical studies and listed as previously mentioned, very rare cases of the following adverse drug reactions have been reported in post-marketing experience: hypersensitivity including anaphylaxis, dyspnoea, nausea, angioneurotic oedema, pruritus, rash, urticaria and weight increased.

No interactions studies have been performed with levocetirizine (including no studies with CYP3A3 inducer); 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 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.

Store below 30°C. Protect from light and moisture.
Shelf-Life: 2 years from the date of manufacture.

Antihistamines & Antiallergics

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

C