Montelukast, the active ingredient in Zokast, is a selective and orally active leukotriene receptor antagonist that inhibits the cysteinyl leukotriene CysLT1 receptor. Montelukast sodium is described chemically as [R (E)]-1-[[[1-[3-[2-(7-chloro-2-quinoliny) ethenyl] phenyl]-3-[2-(1-hydroxy-1-methylethyl) phenyl] thio] methyl] cyclopropaneacetic acid, monosodium salt. The empirical formula is C35CINNaO3S, and its molecular weight is 608.18.
Zokast is indicated for the prophylaxis and chronic treatment of asthma in adults and pediatric patients 2 years of age and older.
Zokast is indicated for prevention of exercise induced bronchoconstriction in patients 6 years of age and older.
Zokast is indicated in adults and pediatric patients 2 years of age and older for the relief of symptoms of seasonal allergic rhinitis and perennial allergic rhinitis.
Dosage and administration
Zokast should be administered once daily without regard of food ingestion. This medicinal product is to be given to a child under adult supervision. The dosage of Zokast for patients of various age groups is as follows
- Adults and adolescents 15 years of age and older: one 10mg tablet once daily.
- Pediatric patients 6 to 14 years of age: one 5mg chewable tablet once daily.
- Pediatric patients 2 to 5 years of age: One 4mg chewable tablet once daily.
Asthma: Zokast should be taken once daily in the evening
Exercise-induced Bronchoconstriction (EIB) 6 years of age and older: For prevention of EIB, a single dose of Zokast should be taken at least 24 hours before exercise.
An additional dose of Zokast should not be taken within 24 hours of a previous dose. Patients already taking Zokast daily for another indication (including chronic asthma) should not take an additional dose to prevent EIB. All patients should have available for rescue a short-acting β-agonist. Safety and efficacy in patients younger than 6 years of age have not been established.
Daily administration of Zokast for the chronic treatment of asthma has not been established to prevent acute episodes of EIB.
Allergic Rhinitis: For allergic rhinitis, Zokast should be taken once daily in the morning or the evening. The time for administration may be individualized to suit patient’s needs.
Asthma and allergic rhinitis: Patients with both asthma and allergic rhinitis should take only on Zokast dose daily in the evening.
Mechanism of action
The cysteinyl leukotrienes (LTC4, LTD4 AND LTE4) are products of arachidonic acid metabolism and are released from various cells, including mast cells and eosinophils. These eicosanoids bind to cysteinyl leukotriene (CysLT) receptors. The CysLT type-1 (CysLT1) receptor is found in the human airway (including airway smooth muscle cells and airway macrophages) and on other pro-inflammatory cells (including eosinophils and certain myeloid stem cells). CysLTs have been correlated with the pathophysiology of asthma and allergic rhinitis. In asthma, leukotriene-mediated effects include airway edema, smooth muscle contraction, and altered cellular activity associated with the inflammatory process. In allergic rhinitis, CysLTs are released from the nasal mucosa after allergen exposure during both early-and late-phase reactions and are associated with symptoms of allergic rhinitis.
Montelukast is an orally active compound that binds with high infinity and selectivity to the CysLT1 receptor (in preference to other pharmacologically important airway receptors, such as the prostanoid, cholinergic, or β-adrenergic receptor). Montelukast inhibits physiologic actions of LTD4 at the CysLT1 receptor without any agonist activity.
Hypersensitivity to the active substance or to any of the excipients.
Warnings and precautions
Acute asthma: Montelukast is not indicated for use in the reversal of bronchospasm in acute asthma attacks, including status asthmaticus. Therapy with Montelukast can be continued during exacerbations of asthma. Patients who have exacerbations of asthma after exercise should have available for rescue a short-acting inhaled β-agonist.
Concomitant Corticosteroid use: While the dose of inhaled corticosteroid may be reduced gradually under medical supervision, Montelukast should not be abruptly substituted for inhaled or oral corticosteroids.
Aspirin sensitivity: Patients with known aspirin sensitivity should continue avoidance of aspirin or non-steroidal anti-inflammatory agents while taking Montelukast.
Neuropsychiatric events: Neuropsychiatric events have been reported in adults, adolescents and pediatric patients taking Montelukast. Post marketing reports with Montelukast use induce agitation, aggressive behavior or hostility, anxiousness, depression, disorientation, dream abnormalities, hallucinations, insomnia, irritability, restlessness, somnambulism, suicidal thinking and behavior (including suicide), and tremor.
Eosinophilic conditions: In rare cases, patients with asthma on therapy with Montelukast may present with systemic eosinophilia, sometimes presenting with clinical features of vasculitis consistent withChurg-Strauss syndrome, a condition which is often treated with systemic corticosteroid therapy. A causal association between Montelukast and these underlying conditions has been established.
Phenylketonurics: Phenylketonuric patients should be informed that the 4mg and 5mg chewable tablets contain phenylalanine, 0.674 and 0.842 mg per 4mg and 5mg chewable tablets, respectively. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.
No dose adjustment is needed when Montelukast is co-administered with theophylline, prednisolone, oral contraceptives, terfenadine, digoxin, warfarin, thyroid hormones, sedative hypnotics, non-steroidal anti-inflammatory agents, benzodiazepines, decongestants, and Cytochrome p450 enzyme inducers.
Blood and lymphatic system disorder: Increased bleeding tendency.
Immune system disorder: hypersensitivity reactions including anaphylaxis, very rarely hepatic eosinophilic infiltration
Psychiatric disorders: agitation including aggressive behavior, anxiousness, dream abnormalities and hallucinations, depression, insomnia, irritability, restlessness, suicidal thinking and behavior (including suicide), tremor.
Nervous system disorders: Drowsiness, paraesthesia/hypoesthesia, very rarely seizures.
Cardiac disorders: palpitations.
Respiratory, thoracic and mediastinal disorders: epistaxis.
Gastrointestinal disorders: diarrhea, dyspepsia, nausea, very rarely pancreatitis, vomiting.
Hepatobiliary disorders: rare cases of cholestatic hepatitis, hepatocellular liver injury, and mixed pattern liver injury have been reported in patients treated with Montelukast.
Skin and subcutaneous tissue disorders: angioedema, bruising, erythema nodosum, pruritus, urticarial.
Musculoskeletal and connective tissue disorders: arthralgia, myalgia including muscle cramps.
General disorders and administration site conditions: edema
Use in specific populations
Pregnancy: Pregnancy category B. There are no adequate and well controlled STUDIES IN PREGNANT WOMEN. Results from animal studies have shown that Montelukast crosses the placenta following oral dosing.
Nursing mothers: Studies in rats have shown that Montelukast is excreted in milk. It is not known if Montelukast is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Montelukast is given to a nursing mother.
Adolescents and pediatric patients: safety and efficacy of Montelukast tablets and chewable tablets have been established in pediatric patients 2 years of age and above. Safety of Montelukast has been established in pediatric patients 6 months of age and above. Suitable formulations of Montelukast, such as granules, may be used in paediatric patients who are less than 2 years of age.
No specific information is available on the treatment of overdosage with Montelukast. In chronic asthma studies, montelukast has been administered at doses up to 200mg/day and 900mg/day for 22 weeks and for approximately a week to adult patients, without clinically important adverse experiences.
There have been reports of acute overdosage in post-marketing experience and clinical studies with Montelukast. These include reports in adults and children with a dose as high as 1000mg. There were no adverse experience in the majority of overdosage reports.
It is not known whether Montelukast is removed by peritoneal dialysis or hemodialysis.