NIKP-Montelukast

NIKP-Montelukast chewable tablet 5 mg: A pale red round biconvex uncoated tablet with printed red-purple Japanese characters on both sides.
NIKP-Montelukast chewable tablet 5 mg contains 5.2 mg montelukast sodium which is equivalent to 5.0 mg of free acid.
Excipients/Inactive Ingredients: D-Mannitol, Microcrystalline Cellulose, Croscarmellose Sodium, Hydroxypropyl Cellulose, Magnesium Stearate, Coloring and Flavoring agents.

Pharmacology: Pharmacodynamics: Montelukast causes potent inhibition of airway cysteinyl leukotriene receptors as demonstrated by the ability to inhibit bronchoconstriction due to inhaled LTD₄ in asthmatic patients. Doses as low as 5 mg cause substantial blockage of LTD₄-induced bronchoconstriction.
Montelukast causes bronchodilation within 2 hours of oral administration; these effects were additive to the bronchodilation caused by a β-agonist.
Clinical studies in adults 15 years of age and older demonstrated there is no additional clinical benefit to montelukast doses above 10 mg once daily. This was shown in two chronic asthma studies using doses up to 200 mg once daily and in one exercise challenge study using doses up to 50 mg, evaluated at the end of the once-daily dosing interval.
Pharmacokinetics: Absorption: For the 5-mg chewable tablet, the C_max is achieved 2 hours after administration in adults in the fasted state. The mean oral bioavailability is 73%. Food does not have a clinically important influence with chronic administration.
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 studies with therapeutic doses, plasma concentrations of metabolites of montelukast are undetectable at steady state in adults and pediatric patients.
In vitro studies using human liver microsomes indicate that cytochrome P450 3A4, 2C8 and 2C9, are involved in the metabolism of montelukast. Based on further in vitro results in human liver microsomes, therapeutic plasma concentrations of montelukast do not inhibit cytochromes P450 3A4, 2C9, 1A2, 2A6, 2C19, or 2D6.
Elimination: The 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 montelukast and its metabolites are excreted almost exclusively via the bile. In several studies, the mean plasma half-life of montelukast ranged from 2.7 to 5.5 hours in healthy young adults. The pharmacokinetics of montelukast are nearly linear for oral doses up to 50 mg.

Montelukast is indicated for pediatric patients 6-14 years of age for the prophylaxis and chronic treatment of asthma, including the prevention of day-and nighttime symptoms, the treatment of aspirin-sensitive asthmatic patients, and the prevention of exercise-induced bronchoconstriction.
Montelukast is indicated for the relief of daytime and nighttime symptoms of allergic rhinitis (seasonal allergic rhinitis in pediatric patients 6-14 years of age).

For mild persistent asthmatic, Montelukast chewable tablet 5 mg should be taken once daily. For moderate to severe asthma, Montelukast chewable tablet 5 mg should be taken once daily concomitantly with inhaled corticosteroids to provide additional benefit. The dose should be taken in the evening and should be chewed thoroughly before swallowing.
For allergic rhinitis, Montelukast chewable tablet 5 mg should be taken once daily in the evening and should be chewed thoroughly before swallowing. In patients who are not adequately controlled on the standard therapy according to specialized physicians' consideration, concomitant administration of Montelukast chewable tablet 5 mg may result in further improvement of symptoms. The time of administration may be individualized to suit patient needs.
General Recommendations: The therapeutic effect of Montelukast on parameters of asthma control occurs within one day. Patients should be advised to continue taking Montelukast while their asthma is controlled, as well as during periods of worsening asthma.
No dosage adjustment is necessary for pediatric patients, for the elderly, for patients with renal insufficiency, or mild-to-moderate hepatic impairment, or for patients of either gender.
Therapy with Montelukast in Relation to Other Treatments for Asthma: Montelukast can be added to a patient's existing treatment regimen.
Reduction in Concomitant Therapy: Bronchodilator Treatments: Montelukast can be added to the treatment regimen of patients who are not adequately controlled on bronchodilator alone. When a clinical response is evident (usually after the first dose), the patient's bronchodilator therapy can be reduced as tolerated.
Inhaled Corticosteroids: Treatment with Montelukast provides additional clinical benefit to patients treated with inhaled corticosteroids. A reduction in the corticosteroid dose can be made as tolerated. The dose should be reduced gradually with medical supervision. In some patients, the dose of inhaled corticosteroids can be tapered off completely. Montelukast should not be abruptly substituted for inhaled corticosteroids.

No specific information is available on the treatment of overdosage with Montelukast. In chronic asthma studies, Montelukast has been administered at doses up to 200 mg/day to adult patients for 22 weeks and in short-term studies, up to 900 mg/day to patients for approximately one week 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 1,000 mg. The clinical and laboratory findings observed were consistent with the safety profile in adults and pediatric patients. There were no adverse experiences in the majority of overdosage reports.
The most frequently occurring adverse experiences were consistent with the safety profile of Montelukast and included abdominal pain, somnolence, thirst, headache, vomiting, and psychomotor hyperactivity.
It is not known whether montelukast is dialyzable by peritoneal or hemodialysis.

Hypersensitivity to any component of this product.

The efficacy of oral Montelukast for the treatment of acute asthma attacks has not been established. Therefore, oral Montelukast Sodium should not be used to treat acute asthma attacks. Patients should be advised to have appropriate rescue medication available. While the dose of concomitant inhaled corticosteroid may be reduced gradually under medical supervision, Montelukast should not be abruptly substituted for inhaled or oral corticosteroids.
Neuropsychiatric events have been reported in patients taking Montelukast (see Adverse Reactions). Since other factors may have contributed to these events, it is not known if they are related to Montelukast. Physicians should discuss these adverse experiences with their patients and/or caregivers. Patients and/or caregivers should be instructed to notify their physician if these changes occur.
In rare cases patients receiving anti-asthma agents, including leukotriene receptor antagonists have experienced one or more of the following: eosinophilia, vasculitis, rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy sometimes diagnosed as Churg-Strauss syndrome, a systemic eosinophilic vasculitis. These cases have been sometimes associated with the reduction or withdrawal of oral corticosteroid therapy. Although a causal relationship with leukotriene receptor antagonism has not been established, caution and appropriate clinical monitoring are recommended in patients receiving Montelukast.
Use in Children: Safety and effectiveness in pediatric patients younger than 6 months of age have not been studied. Studies have shown that Montelukast does not affect the growth rate of pediatric patients.
Use in the Elderly: In clinical studies, there were no age-related differences in the efficacy or safety profiles of Montelukast.

Pregnancy: Montelukast has not been studied in pregnant women. Montelukast should be used during pregnancy only if clearly needed. During worldwide marketing experience, congenital limb defects have been rarely reported in the offspring of women being treated with Montelukast during pregnancy. Most of these women were also taking other asthma medications during their pregnancy. A causal relationship between these events and Montelukast has not been established.
Breastfeeding: 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 breastfeeding mother.

Montelukast has been generally well tolerated. Side effects, which usually were wild, generally did not require discontinuation of therapy. The overall incidence of side effects reported with Montelukast was comparable to placebo.
Pediatric Patients 6 to 14 Years of Age with Asthma: Montelukast has been evaluated in approximately 475 pediatric patients 6 to 14 years of age. The safety profile in pediatric patients is generally similar to the adult safety profile and to placebo.
In an 8-week, placebo-controlled clinical study, the only adverse experience reported as drug related in >1% of patients treated with Montelukast and at a greater incidence than in patients treated with placebo was headache. The incidence of headache was not significantly different in the two treatment groups.
In studies evaluating growth rate, the safety profile in these pediatric patients was consistent with the safety profile previously described for Montelukast.
Cumulatively, 263 pediatric patients 6 to 14 years of age were treated with Montelukast for at least 3 months and 164 for 6 months or longer. With prolonged treatment, the adverse experience profile did not change.
Pediatric Patients 2 to 14 Years of Age with Seasonal Allergic Rhinitis: Montelukast has been evaluated in 280 pediatric patients 2 to 14 years of age and older with perennial allergic rhinitis in a 2-week, placebo-controlled, clinical study. Montelukast administered once daily in the evening was generally well tolerated with a safety profile similar to that of placebo. In this study, no adverse experiences reported as drug related ≥1% of patients treated with Montelukast and at a greater incidence of somnolence was similar to that of placebo.
Post marketing Experience: The following side effects have been reported in post marketing use: Infections and infestations: upper respiratory infection.
Blood and lymphatic system disorders: increased bleeding tendency, thrombocytopenia.
Immune system disorders: hypersensitivity reactions including anaphylaxis, hepatic eosinophilic infiltration.
Psychiatric disorders: agitation including aggressive behavior or hostility, anxiousness, depression, disorientation, disturbance in attention, dream abnormalities, dysphemia (stuttering), hallucinations, insomnia, memory impairment, obsessive-compulsive symptoms, psychomotor hyperactivity (including irritability, restlessness and tremor), somnambulism, suicidal thinking and behavior (suicidality), tic.
Nervous system disorders: dizziness, drowsiness, paraesthesia/hypoesthesia, seizure.
Cardiac disorders: palpitations.
Respiratory, thoracic and mediastinal disorders: epistaxis, pulmonary eosinophilia.
Gastrointestinal disorders: diarrhea, dyspepsia, nausea, vomiting.
Hepatobiliary disorders: increased ALT and AST, hepatitis (including cholestatic, hepatocellular, and mixed-pattern liver injury).
Skin and subcutaneous tissue disorders: angioedema, bruising, erythema multiforme, erythema nodosum, pruritus, rash, urticaria.
Musculoskeletal and connective tissue disorders: arthralgia, myalgia including muscle cramps.
Renal and urinary disorders: enuresis in children.
General disorders and administration site conditions: asthenia/fatigue, edema, pyrexia.

Montelukast may be administered with other therapies routinely used in the prophylaxis and chronic treatment of asthma, and in the treatment of allergic rhinitis. In drug-interactions studies, the recommended clinical dose of montelukast did not have clinically important effects on the pharmacokinetics of the following drugs: theophylline, prednisone, prednisolone, oral contraceptives (ethinyl estradiol/norethindrone 35/1), terfenadine, digoxin and warfarin.
The area under the plasma concentration-time curve (AUC) for montelukast was decreased approximately 40% in subjects with co-administration of Phenobarbital. No dosage adjustment for Montelukast is recommended.
In vitro studies have shown that montelukast is an inhibitor of CYP 2C8. However, data from a clinical drug-drug interaction study involving montelukast and rosiglitazone (a probe substrate representative of drugs primarily metabolized by CYP 2C8) demonstrated that montelukast does not inhibit CYP 2C8 in vivo. Therefore, montelukast is not anticipated to alter the metabolism of drugs metabolized by this enzyme (e.g., paclitaxel, rosiglitazone, repaglinide).
In vitro studies have shown that montelukast is a substrate of CYP 2C8, 2C9, and 3A4. Data from a clinical drug-drug interaction study involving montelukast and gemfibrozil (an inhibitor of both CYP 2C8 and 2C9) demonstrated that gemfibrozil increased the systemic exposure of montelukast by 4.4-fold. Co-administration of itraconazole, a strong CYP 3A4 inhibitor, with gemfibrozil and montelukast did not further increase the systemic exposure of montelukast. The effect of gemfibrozil on systemic exposure of montelukast is not considered to be clinically meaningful based on clinical safety data with doses greater than the 10 mg approved dose in adults (e.g., 200 mg/day to adult patients for 22 weeks, and up to 900 mg/day to patients for approximately one week) where clinically important adverse experiences were not observed. Therefore, no dosage adjustment of montelukast is required upon co-administration with gemfibrozil. Based on in vitro data, clinically important drug interactions with other known inhibitors of CYP 2C8 (e.g., trimethoprim) are not anticipated. In addition, co-administration of montelukast with itraconazole alone resulted in no significant increase in the systemic exposure of montelukast.

Chewable tablets: Store below 30°C. Protect from moisture and light.

Antiasthmatic & COPD Preparations

R03DC03 - montelukast ; Belongs to the class of leukotriene receptor antagonists. Used in the systemic treatment of obstructive airway diseases.

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