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Brand Name, Dosage Format and Strength
Kastair EZTab 5 mg TABLET
Therapeutic Category
Respiratory System
Class
Corticosteroid, Anticholinergic, Beta2-Agonist, Leukotriene Inhibitor, Beta2-Agonist, Beta2-Agonist, Expectorant, Antiasthma-Beta2- Agonist, Mucolytic, Beta2-Agonist, Mucolytic, Antitussive, Nasal Decongestant, Analgesic-Antipyretic, Antitussive, Nasal Decongestant, Analgesic-Antipyretic, Nasal Decongestant, Antihistamine, Nasal Decongestant, Antihistamine, Analgesic-Antipyretic, Nasal Decongestant, Analgesic-Antipyretic, Alpha Adrenergic Agonist, Nasal Decongestant, Antihistamine, Analgesic-Antipyretic
CLINICAL PHARMACOLOGY
Pharmacodynamics
Montelukast is a selective leukotriene receptor antagonist that binds to CysLT1 receptor. The cysteinyl leukotrienes (LTC4, LTD4, and LTE4) are formed from the metabolism of arachidonic acid and are produced by a number of cells including eosinophils, basophils, mast cells, macrophages, and monocytes. The effects of these eicosanoids are mediated by binding to cysteinyl leukotriene (CysLT) receptors. The CysLT type-1 (CysLT1) receptor is present in various contractile tissues including airway smooth muscle cells. CysLTs contribute to the pathophysiology of asthma and allergic rhinitis. In asthma, CysLTs are found to increase mucus secretion and vascular permeability, airway edema, bronchoconstriction, and altered cellular activity associated with the inflammatory process. In allergic rhinitis, CysLTs are released within minutes from the nasal mucosa after exposure to allergens. This release leads to inflammation and symptoms such as nasal congestion and rhinorrhea. Montelukast inhibits bronchoconstriction and reduces nasal mucosa inflammation induced by exposure to known precipitants.
Pharmacokinetics
Montelukast is readily absorbed after oral administration. Cmax of montelukast is achieved within 2 hrs (Tmax) after oral administration of a 4 mg chewable tablet to fasted children 2 to 5 years old.
After oral administration of a 5 mg EZTab to fasted adults, Cmax of montelukast (252.71 ± 63.6 ng/mL) is achieved within 2.75 ± 0.77 hrs (Tmax). The elimination half life of montelukast is 4.23 ± 1.238 hrs.
In two pharmacokinetic trials by Knorr, et al., in asthmatic pediatric patients aged 2 to 5 yrs (2001) and 6 to 14 yrs (1999), Cmax of montelukast 4 mg (471 ± 65 ng/mL) and 5 mg (495 ± 129 ng/mL) as chewable tablets are attained within 2.07± 0.3 hrs and 2.6 ± 1 hrs, respectively.
After oral administration of a 10 mg film-coated tablet to fasted adults, Cmax of montelukast is achieved in 2 to 4 hrs (Tmax); the mean oral bioavailability is 64%. The oral bioavailability and Cmax are not influenced by a standard meal in the morning.
The mean systemic exposure of the 4 mg and 5 mg tablet in children 2 yrs to 5 yrs and 6 yrs to 14 yrs old, respectively, is similar to the mean systemic exposure of the 10 mg tablet in adults.
Montelukast’s steady state volume of distribution is 8 to 11 L. Plasma protein binding is more than 99%.
Montelukast is metabolized in the liver by CYP-450 enzymes 3A4, 2A6, and 2C9. Plasma concentrations of montelukast metabolites are undetectable at steady state in studies in adults and children using therapeutic doses. Metabolism in patients with mild to moderate hepatic impairment is reduced; elimination half life is prolonged. Montelukast is excreted mainly in the feces via the bile as unchanged drug and metabolites.
Animal studies indicate that montelukast crosses the placenta in rats and rabbits and is distributed into milk in rats after oral administration; in humans, it is not known whether the drug crosses the placenta or distributes in milk.