Montelukast Sodium

FORMULATION
Each Chewable tablet contains
Montelukast (as sodium)

Pharmacology
Mechanism of action
The cysteinyl leukotrienes (LTC„ LTD4, LTE4) are products of arachidonic acid metabolism and are released from various cells, including mast cells and eosinophils. These eicosanoids bind to cysteinyl leukotriene receptors (CysLT1) found in the human airway. Cysteinyl leukotrienes and leukotriene receptor occupation have been correlated with the pathophysiology of asthma, including airway edema, smooth muscle contraction, and altered cellular activity associated with the inflammatory process, which contribute to the signs and symptoms of asthma.
Montelukast is an orally active compound that binds with high affinity and selectivity to the CysLTl receptor (in preference to other pharmacologically important airway receptors, such as the prostanoid, cholinergic, or ß-adrenergic receptor). Montelukast inhibits physiologic actions of LTD4 at the CysLT1 receptor without any agonist activity.

PHARMACOKINETICS
Absorption
Montelukast is rapidly absorbed following oral administration the mean peak Montelukast plasma concentration (Cmax) is achieved in 3 to 4 hours (Tmax). The mean oral bioavailability is 64%. The oral bioavailability and Cmax are not influenced by a standard meal in the morning. For the 5 mg chewable tablet, the mean Cmax is achieved in 2 to 2.5 hours after administration to adults in the fasted state. The mean oral bioavailability is 73% in the fasted state versus 63% when administered with a standard meal in the morning. The safety and efficacy of Montelukast were demonstrated in clinical trials in which both formulations were administered in the evening without regard to the timing of food ingestion. The comparative pharmacokinetics of Montelukast, when administered as two 5 mg chewable tablets versus one 10 mg film-coated tablet, have not been evaluated.

Distribution
Montelukast is more than 99% bound to plasma proteins. The steady-state volume of distribution of Montelukast averages 8 to 11 liters. Studies in rats with radiolabeled Montelukast indicate minimal distribution across the blood-brain barrier. In addition, concentrations of radiolabeled material at 24 hours post-dose were minimal in all other tissues.

Metabolism
Montelukast is extensively metabolized in the liver.

Elimination
The plasma clearance of Montelukast averages 45 mL/min in healthy adults

Special Populations
Gender: The pharmacokinetics of Montelukast are similar in males and females.
Elderly: The pharmacokinetic profile and the oral bioavailability of a single 1 Omg oral dose of Montelukast
are similar in elderly and younger adults. The plasma half-life of Montelukast is slightly longer in the elderly.
No dosage adjustment in the elderly is required.
Hepatic Insufficiency: No dosage adjustment is required in patients with mild to moderate hepatic insufficiency.
Renal Insufficiency: Since Montelukast and its metabolites are not excreted in the urine, no dosage adjustment is recommended in these patients.

INDICATIONS
Prophylaxis and chronic treatment of bronchial asthma in adults and paediatric patients 2 years of age and older.

DOSAGEANDADMINISTRATION
Adolescents and adults 15 years of age and older:
The dosage for adults & adolescents 15 years of age and older is one 10-mg tablet daily to be taken in the evening.

Pediatric patients 6 to 14 years of age
The dosage for pediatric patients 6 to 14 years of age is one 5-mg chewable tablet daily to be taken in the evening. No dosage adjustment within this age group is necessary.

Pediatric patients 2 to 5 years of age
The dosage for pediatric patients 2 to 5 years of age is one 4-mg chewable tablet daily to be taken in the evening. No dosage adjustment within this age group is necessary.

CONTRAINDICATIONS
Hypersensitivity to any component of this product.

PRECAUTIONS
General
Montelukast is not indicated for use in the reversal of bronchospasm in acute asthma attacks, including status asthmaticus. Patients should be advised to have appropriate rescue medication available. Therapy with Montelukast can be continued during acute exacerbations of asthma. While the dose of inhaled corticosteroid may be reduced gradually under medical supervision, Montelukast should not be abruptly substituted for inhaled or oral corticosteroids. Montelukast should not be used as monotherapy for the treatment and management of exercise-induced bronchospasm.

Pregnancy
Teratogenic Effects, Pregnancy Category B: No teratogenicity was observed, however, there are no adequate and well-controlled studies in pregnant women. Montelukast should be used during pregnancy only if clearly needed.

Pediatric Use
The safety and effectiveness in pediatric patients below the age of2 years have not been established.

ADVERSE EFFECTS
Most common adverse events are asthenia/fatigue, fever, abdominal pain.

OVERDOSAGE
Adolescents and adults 15 years of age and older:
The dosage for Adults & Adolescents 15 years of age and older is one 10-mg tablet daily to be taken in the evening.

DRUG – DRUG INTERACTIONS
Montelukast was used concomitantly with a wide range of commonly prescribed drugs in clinical studies without evidence of clinical adverse interactions. These medications included theophylline, warfarin, digoxin, prednisolone, thyroid hormones, sedative hypnotics, non-steroidal anti-inflammatory agents, benzodiazepines, and decongestants.
It is reasonable to employ appropriate clinical monitoring when potent cytochrome P450 enzyme inducers, such as phenobarbital or rifampin, are co-administered with Montelukast.

CAUTION
Foods, Drugs, Devices and Cosmetics Act prohibits dispensing without prescription.

STORAGE CONDITION
Store at temperatures not exceeding 300C. Protect from moisture.

KEEP ALL MEDICINES OUT OF REACH OF CHILDREN.

AVAILABILITY
Montelukast 5 mg Tablet
Strip foil x 10’s (Box of 30’s).

“For suspected adverse drug reaction, report to the FDA: www.fda.gov.ph“.