Sunday, June 21, 2009

COMPOSITION

Each uncoated tablet contains:
Montelukast sodium equivalent to Montelukast .........................................................10 mg Levocetirizine dihydrochloride I.P. ……………..5 mg Colour-Ponceau-4R

DESCRIPTION

Montelukast is a
leukotriene receptor antagonist (LTRA) used for the maintenance treatment of asthma and to relieve symptoms of seasonal allergies. It is usually administered orally.

Levocetirizine is the R-enantiomer of cetirizine. Levocetirizine is an orally active, potent, selective and long acting H1-histamine receptor antagonist with no anticholinergic activity.

It has been demonstrated by recent studies that the treatment of AR with concomitant administration of an antileukotriene (montelukast) and an antihistamine (levocetrizine), shows significantly better symptom relief compared with the modest improvement of rhinitis symptomatology with each of the treatments alone.

Montelukast was approved by FDA in 1998

PHARMACOLOGY

PHARMACODYNAMICS

Montelukast:
Montelukast is a
CysLT1 antagonist; that is it blocks the action of leukotriene D4 on the cysteinyl leukotriene receptor CysLT1 in the lungs and bronchial tubes by binding to it. This reduces the bronchoconstriction otherwise caused by the leukotriene, and results in less inflammation

Because of its method of operation, it is not useful for the treatment of acute asthma attacks. Again because of its very specific focus of operation, it does not interact with other allergy medications such as theophylline.

The Mont in Montelukast stands for Montreal, the place where Merck developed the drug (Singulair)

Leukotrienes are chemical substances that are responsible for an inflammatory response in the lower respiratory pathway, in bronchus and lung. Leukotrienes are produced in the body from
arachidonic acid by the enzyme 5-lipoxygenase. Their production by the body is part of a complex response that usually includes the production of histamine therefore anti-histaminics are also needed to inhibit the trigger


Levocetirizine,

the (R) enantiomer of cetirizine, is a potent and selective antagonist of peripheral H 1 -receptors

Benefit of combination
Levocetirizine is highly effective in relieving the symptoms of seasonal & perennial allergic rhinitis including sneezing ,pruritus & rhinorrhoea
Montelukast has shown particular benefit in improving night time symptoms of allergic rhinitis: including difficult in going to sleep ,nasal congestion & night time awakening.
Pharmacokinetics

Montelukast

Ø AbsorptionAfter administration of the 10-mg film-coated tablet to fasted adults, the mean peak montelukast plasma concentration (C max ) is achieved in 3 to 4 hours (T max ). The mean oral bioavailability is 64%. The oral bioavailability and C max are not influenced by a standard meal in the morning.
Ø DistributionMontelukast is more than 99% bound to plasma proteins. The steady-state volume of distribution of montelukast averages 8 to 11 litres.
Ø MetabolismMontelukast is extensively metabolized. In studies with therapeutic doses, plasma concentrations of metabolites of montelukast are undetectable at steady state in adults and pediatric patients.
Ø EliminationThe plasma clearance of montelukast averages 45 mL/min in healthy adults. Following an oral dose of radiolabeled montelukast, 86% of the radioactivity was recovered in 5-day fecal collections and <0.2% was recovered in urine. Coupled with estimates of montelukast oral bioavailability, this indicates that montelukast and its metabolites are excreted almost exclusively via the bile.

Levocetirizine
The pharmacokinetics of levocetirizine are linear with dose and time independent with low inter-subject variability.
Ø Absorption: Levocetirizine is rapidly and extensively absorbed following oral administration. Peak plasma concentrations are achieved 0.9 g h after dosing. Steady state is achieved after two days. The extent of absorption is dose-independent and is not altered by food, but the peak concentration is reduced and delayed.
Ø 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 0.4 l/kg.
Ø Metabolism 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.Due to its low metabolism and absence of metabolic inhibition potential, the interaction of levocetirizine with other substances, or vice-versa, is unlikely. The plasma half-life in adults is 7.9 + 1.9 hours..
Ø Excretion
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.



INDICATIONS
Seasonal Allergic Rhinitis.
Perennial Allergic Rhinitis.
Allergic Rhinitis with asthma.
Exercise induced bronchoconstriction.

DOSAGE
Adults 15 yrs & above 1 tablet OD with or without food

Renal impairmentAs levocetirizine is mainly excreted through urine, dosage adjustment may be required in patients with impaired renal function. Hence this combination should be used with caution in such patients.

Hepatic ImpairmentAs montelukast is mainly excreted through bile, caution is to be exercised while prescribing this combination in patients with impaired hepatic function.

PregnancyThere are no adequate and well controlled studies of either montelukast or levocetirizine in pregnant women. Hence this combination should not be used during pregnancy.
LactationSince levocetirizine is excreted in breast-milk the combination is not recommended during lactation
Elderly
No dosage adjustment in the elderly is required.

STORAGE
Store in a cool dry place

PRESENTATION
Strip of 10 Tablets.


No comments:

Post a Comment

There was an error in this gadget