Kastair EZ Tab/Kastair

Kastair EZ Tab: It is a white, round tablet with red specks, with EZ logo on one side and plain on the other side. Easy to swallow, cherry-flavored tablet that melts in the mouth in less than 30 seconds without chewing.
Montelukast (Kastair EZ Tab) 4 mg tablet contains 4.2 mg montelukast sodium equivalent to 4 mg of montelukast.
Montelukast (Kastair EZ Tab) 5 mg tablet contains 5.2 mg montelukast sodium equivalent to 5 mg of montelukast.
Kastair: Montelukast (Kastair) 4 mg oral granules is a white, homogenous powder.
Each sachet of granules contains: Montelukast (as sodium) (equivalent to 4.15 mg montelukast sodium) 4 mg.

Leukotriene Receptor Antagonist.
Pharmacology: Pharmacodynamics: Montelukast is a selective leukotriene-receptor antagonist that specifically inhibits the cysteinyl leukotriene CysLT₁ receptor. The cysteinyl leukotrienes [CysLT (LTC₄, LTD₄, and LTE₄)] are potent inflammatory eicosanoids released from various cells including mast cells and eosinophils that bind to CysLT receptors. The CysLT type 1 (CysLT₁) receptor is present in the human airway (including airway smooth muscle cells and airway macrophages). CysLTs contribute to the pathophysiology of asthma and allergic rhinitis. In asthma, CysLTs are found to increase mucus secretion, vascular permeability, and bronchoconstriction. In allergic rhinitis, CysLTs are released from the nasal mucosa after exposure to allergens and are associated with symptoms of allergic rhinitis. Montelukast inhibits bronchoconstriction and reduces inflammation of the nasal mucosa induced by exposure to known precipitants.
Pharmacokinetics: Kastair EZ Tab: Montelukast's steady state volume of distribution is 8 to 11 liters. Plasma protein binding is more than 99%.
4 mg: Montelukast is rapidly absorbed after oral administration. After administration of 10 mg film-coated tablet in adults in the fasted state, mean peak montelukast plasma concentration (C_max) is achieved in 3 to 4 hours. The mean oral bioavailability is 64%. The oral bioavailability and C_max are not influenced by a standard meal in the morning.
In a pharmacokinetic trial in asthmatic pediatric patients aged 2 to 5 years, peak plasma concentration of montelukast 4 mg (471±65 ng/mL) as chewable tablet is attained within 2.07±0.3 hours.
Montelukast is extensively metabolized in the liver by cytochrome P450 (CYP) isoenzymes CYP2C8, CYP3A4, and CYP2C9. Plasma concentrations of montelukast metabolites are undetectable at steady state in studies using therapeutic doses in adults and children.
Montelukast is excreted mainly in the feces via the bile as unchanged drug and metabolites.
Special Population: Hepatic Impairment: Patients with mild to moderate hepatic impairment and cirrhosis had evidence of decreased metabolism of montelukast resulting in 41% increase in mean area under the plasma concentration-time curve (AUC). The elimination of montelukast is prolonged in these patients relative to patients with normal hepatic function.
5 mg: In a pharmacokinetic trial in asthmatic patients aged 6 to 14 years, peak plasma concentration of Montelukast 5 mg 495±129 ng/mL as chewable tablet is attained within 2.6±1 hour.
Montelukast is extensively metabolized in the liver by cytochrome P450 isoenzymes CYP2C8, CYP3A4, and CYP2C9, and is excreted principally in the feces via the bile.
Bioequivalence Study: Montelukast sodium (Kastair EZ Tab) 5 mg tablet was shown to be bioequivalent to the reference product (innovator) in adults under fasting conditions. The following are important pharmacokinetic parameters of montelukast in adult volunteers who received montelukast sodium (Kastair EZ Tab) 5 mg tablet (as a single oral dose) under fasting conditions: See Table 1.

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Kastair: Montelukast is rapidly absorbed after oral administration.
In a pharmacokinetic trial in asthmatic pediatric patients 6 to 24 months old, peak plasma concentrations (514.4 ng/mL) of montelukast 4 mg as oral granules are attained within 2.2 hours.
Montelukast's steady state volume of distribution is 8 to 11 liters. Plasma protein binding is more than 99%.
Montelukast is extensively metabolized in the liver by cytochrome P450 isoenzymes CYP2C8, CYP3A4, and CYP2C9, and is excreted principally in the feces via the bile.

Kastair EZ Tab: For the relief of symptoms of allergic rhinitis: Seasonal allergic rhinitis in children 2 years and older and in adults; Perennial allergic rhinitis in children 6 months old and older and in adults.
For the prophylaxis and chronic treatment of asthma in children 6 months old and older and in adults.
Montelukast is effective alone or when used together with other agents for the management of chronic asthma. Montelukast may be used concomitantly with inhaled corticosteroids to control asthma and to reduce the dose of inhaled corticosteroids required by patients with moderate to severe asthma.
For the prevention of exercise-induced bronchoconstriction in children 2 years and older and in adults.
Kastair: For the prophylaxis and chronic treatment of asthma in children 6 months old to 5 years old.
For the relief of symptoms of allergic rhinitis: Seasonal allergic rhinitis in children 2 to 5 years old; Perennial allergic rhinitis in children 6 months old to 5 years old.
For the prevention of exercise-induced bronchoconstriction in children 2 to 5 years old.

Kastair EZ Tab: 4 mg: Montelukast 4 mg tablet can be dissolved in the mouth or chewed before swallowing.
This medicine may be taken with or without food. (See Table 2.)

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*For younger children (6 months to 2 years old), montelukast 4 mg tablet can be: Administered directly in the mouth, or; the tablet can be crushed or mixed with a spoonful of one of the following soft foods at cold or room temperature: applesauce, mashed carrots, rice, or ice cream; or, dissolved in 5 mL (1 teaspoonful) of cold or room temperature breast milk or baby formula.
The crushed tablet should not be dissolved in liquid other than breast milk or baby formula. However, liquids can be taken after administration.
The tablet should not be crushed until ready for use.
The entire dose of the crushed tablet must be administered within 15 minutes. The crushed tablet should not be stored for future use if dissolved in breast milk or baby formula or mixed with food.
For patients with allergic rhinitis: The time of administration may be individualized to suit patient needs.
For patients with asthma with or without coexisting allergic rhinitis: The dose should be taken in the evening to obtain simultaneous peak plasma concentration and peak airway reactivity in the morning.
Take at regular intervals (i.e., daily) to be therapeutically effective, even if the patient has no asthma symptoms, or as prescribed by a physician.
For the prevention of exercise-induced bronchoconstriction: Take at least 2 hours before exercise.
Do not take an additional dose within 24 hours of a previous dose.
Do not take an additional dose to prevent exercise-induced bronchoconstriction if the patient is taking montelukast daily for chronic asthma or allergic rhinitis. Consult a physician about treatment of exercise-induced bronchoconstriction (see Precautions).
5 mg: See Table 3.

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Directions for Use: For patients with allergic rhinitis: The time of administration may be individualized to suit patient needs.
Take everyday, at about the same time each day, or, as prescribed by a physician.
For patients with asthma with or without coexisting allergic rhinitis: The dose should be taken in the evening to obtain simultaneous peak plasma concentration and peak airway reactivity in the morning.
Take at regular intervals (i.e., daily) to be therapeutically effective, even if the patient has no asthma symptoms, or, as prescribed by a physician.
For the prevention of exercise-induced bronchoconstriction: Take at least 2 hours before exercise.
Do not take an additional dose within 24 hours of a previous dose.
Do not take an additional dose to prevent exercise-induced bronchoconstriction if the patient is taking montelukast daily for chronic asthma or allergic rhinitis. Consult a physician about treatment of exercise-induced bronchoconstriction.
Montelukast 5 mg tablet can be dissolved in the mouth or chewed before swallowing.
May be taken with or without food.
Kastair: This medicine should be taken orally, once a day, with or without food. (See Table 4.)

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Directions for Use: *For younger children (6 months to 2 years old), montelukast 4 mg granules can be: Administered directly in the mouth, or mixed with a spoonful of one of the following soft foods at cold or room temperature: applesauce, mashed carrots, rice, or ice cream; or, dissolved in 5 mL (1 teaspoonful) of cold or room temperature breast milk or baby formula.
The granules should not be dissolved in liquid other than breast milk or baby formula.
However, liquids can be taken after administration.
The sachet should not be opened until ready for use.
The entire dose of the sachet must be administered within 15 minutes. The granules should not be stored for future use if dissolved in breast milk or baby formula or mixed with food.
For patients with asthma with or without coexisting allergic rhinitis: The dose should be taken in the evening to obtain simultaneous peak plasma concentration and peak airway reactivity in the morning.
Montelukast is effective alone or when used together with other agents for the management of chronic asthma. Montelukast may be used concomitantly with inhaled corticosteroids to control asthma and to reduce the dose of inhaled corticosteroids required by patients with moderate to severe asthma.
For patients with allergic rhinitis: The time of administration may be individualized to suit patient needs.
For the prevention of exercise-induced bronchoconstriction: Take at least 2 hours before exercise.
Do not take an additional dose within 24 hours of a previous dose.
Do not take an additional dose to prevent exercise-induced bronchoconstriction if the patient is taking montelukast daily for chronic asthma or allergic rhinitis.

Montelukast given in doses up to 200 mg/day for 22 weeks and up to 900 mg/day for approximately a week to adult patients showed no clinically important adverse reactions. Acute overdosages in adults and children given montelukast with a dose as high as 1000 mg have been reported. There were no adverse effects reported in majority of overdosage reports. The most frequent adverse effects observed were abdominal pain, headache, psychomotor hyperactivity, somnolence, thirst, vomiting, and less frequently convulsion.
There is no specific information available on the treatment of overdosage with montelukast. In case of overdose, institute supportive and symptomatic therapy, i.e., remove unabsorbed material from the gastrointestinal tract. There is no adequate evidence to support the use of dialysis in the treatment of montelukast overdose.

Hypersensitivity to Montelukast or other ingredients in the product.

Kastair EZ Tab 4 mg: Risks for Serious Neuropsychiatric Events: Serious neuropsychiatric events have been reported with the use of montelukast. The highly variable types of neuropsychiatric events reported with montelukast included, but are not limited to, agitation, aggression, depression, sleep disturbances, suicidal thoughts and behavior (including suicide).
Because of the risk of neuropsychiatric events, the benefits of montelukast may not outweigh the risks in some patients, particularly when the symptoms of disease may be mild and adequately treated with alternative therapies.
The benefits and risks of montelukast should be discussed with patients and/or caregivers.
The use of montelukast should be reserved for patients with allergic rhinitis who have an inadequate response or intolerance to alternative therapies. In patients with asthma or exercise-induced bronchoconstriction, the benefits and risks should be considered before prescribing montelukast.
When taking montelukast, patients and/or caregivers must be alert for any changes in behavior or new neuropsychiatric symptoms. If changes in behavior are observed, or if new neuropsychiatric symptoms or suicidal thoughts and/or behavior occur, patients should be advised to discontinue montelukast and to contact a physician immediately.

Kastair EZ Tab 4 mg: Neuropsychiatric Events: Neuropsychiatric events have been reported in adult, adolescent and pediatric patients taking montelukast with or without a previous history of psychiatric disorders. These postmarketing reports include agitation, aggressive behavior or hostility, anxiousness, depression, disorientation, disturbance in attention, dream abnormalities, dysphemia, hallucinations, insomnia, irritability, memory impairment, obsessive-impulsive disorders, restlessness, somnambulism, suicidal thoughts and behavior (including completed suicide), tic, and tremor. Patients should inform their physician if these changes occur.
Patients should discontinue montelukast and inform their physician immediately if these changes or new neuropsychiatric symptoms occur. Neuropsychiatric events have been reported mostly during montelukast treatment, but some were reported after discontinuation of montelukast treatment. Therefore, continuous monitoring and supportive care is recommended until symptoms have resolved. If neuropsychiatric events occur, the benefits and risks of restarting treatment with montelukast must be re-evaluated.
Eosinophilic Conditions: Eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy consistent with Churg-Strauss syndrome have been reported in patients with asthma being treated with montelukast. In almost all cases, these events were associated with reduction (tapered dosage) or withdrawal of oral or high-dose inhaled corticosteroid therapy. Patients and/or caregivers should be advised to report symptoms (i.e., feeling of pins and needles, numbness of extremities, flu-like symptoms, rash, sinusitis) immediately to their physician.
Aspirin Sensitivity: Patients with known aspirin sensitivity should be advised to avoid aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) while taking montelukast. Although montelukast can improve airway function in asthmatics with aspirin sensitivity, the drug has not been shown to shorten the bronchoconstrictor response to aspirin or other NSAIDs in such patients.
Acute Asthma: Montelukast is not indicated for the treatment of acute asthma attacks, including status asthmaticus. Patients should have appropriate rescue medications (e.g., short-acting inhaled β-agonist) available to treat asthma exacerbations. However, therapy with montelukast can be continued during acute asthmatic attacks.
While using montelukast, patients should consult a physician for medical advice if more than the recommended dose of short-acting inhaled bronchodilators is needed.
Patients taking montelukast should not discontinue or reduce the dosage of other medicines for asthma unless directed by a physician.
Exercise-induced bronchospasm: Montelukast should not be used as monotherapy for prevention of exercise-induced bronchospasm. Patients who experience exacerbations of asthma after exercise should continue their usual regimen of inhaled β-agonist for prophylaxis and have a short-acting orally inhaled β-agonist available for rescue. Daily administration of montelukast for the chronic treatment of asthma has not been established to prevent acute episodes of exercise-induced bronchospasm.
Concomitant Use with Corticosteroids: While the dose of inhaled corticosteroids may be reduced gradually under medical supervision, montelukast should not be abruptly substituted for inhaled or oral corticosteroids.
Renal Impairment: No dosage adjustment is required for patients with renal impairment.
Hepatic Impairment: No dosage adjustment is necessary for patients with mild to moderate hepatic impairment. There is no available data on patients with severe hepatic impairment or hepatitis.
Kastair EZ Tab 5 mg/Kastair: Acute Asthma: Montelukast is not indicated for the treatment of acute asthma attacks, including status asthmaticus. Patients should have appropriate short-acting inhaled beta-agonist medication available to treat asthma exacerbations. However, therapy with montelukast can be continued during acute asthmatic attacks.
Patients taking montelukast should not discontinue or reduce the dosage of other medicines for asthma unless directed by a physician.
Aspirin Sensitivity: Avoid aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) while taking montelukast in patients with known aspirin sensitivity.
Neuropsychiatric Events: Neuropsychiatric events have been reported in patients taking montelukast. These postmarketing reports include agitation, aggressive behavior or hostility, anxiousness, depression, disorientation, disturbance in attention, dream abnormalities, hallucinations, insomnia, irritability, memory impairment, restlessness, somnambulism, suicidal thinking and behavior (including suicide), and tremor. Patients should inform their physician if these changes occur.
Eosinophilic Conditions: Eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy consistent with Churg-Strauss syndrome have been reported in patients with asthma being treated with montelukast.
Effects on Ability to Drive and Use Machines: Montelukast is not expected to affect patients' physical coordination (e.g., driving, operating machinery). However, in very rare cases, individuals have reported dizziness or drowsiness.
Use in Children: Kastair EZ Tab 4 mg: The safety and effectiveness of montelukast in pediatric patients vary depending on the therapeutic indication. The efficacy and safety of the drug in this population are supported by adequate and well-controlled studies and by extrapolation from demonstrated efficacy studies in various age groups, including adolescents and adults.
Data on montelukast 4 mg tablet and granules have not been established in patients with asthma below 6 months of age, patients with perennial allergic rhinitis below 6 months of age; patients with seasonal allergic rhinitis below 2 years of age, and patients with exercise-induced bronchoconstriction below 2 years of age.
Kastair EZ Tab 5 mg/Kastair: The safety and efficacy of Montelukast in infants younger than 6 months old have not been established.
Use in the Elderly: Kastair EZ Tab: There were no age-related differences in the efficacy or safety profile of montelukast, but greater sensitivity of some older individuals cannot be ruled out. No dosage adjustment is required for the elderly.

Pregnancy: Kastair EZ Tab: Pregnancy Category B. No adequate and well-controlled studies in pregnant women are available for montelukast. Montelukast should only be used during pregnancy when clearly needed.
There have been reports of congenital limb defects in children of patients treated with montelukast. Some of the mothers, however, were receiving various medications in the course of their pregnancies. Since there is no consistent pattern of congenital abnormality development, a relationship between the use of montelukast and the development of congenital anomalies cannot be established.
Lactation: Kastair EZ Tab 4 mg: A published clinical lactation study reported the presence of montelukast in human milk. Data available on the effects of the drug on infants, either directly or through breast milk, do not suggest a significant risk of adverse reactions from exposure to montelukast. The effects of the drug on milk production are unknown. Therefore, do not administer to breastfeeding women unless, in the opinion of a physician, the potential benefit of the drug justifies the possible risk to the infant.
Kastair EZ Tab 5 mg: It is not known if montelukast is excreted in human milk. Therefore, do not administer to breastfeeding women unless, in the opinion of a physician, the potential benefit of the drug justifies the possible risk to the infant.

The most frequently reported adverse effects with montelukast include upper respiratory tract infection, fever, headache, pharyngitis, cough, abdominal pain, diarrhea, otitis media, influenza, rhinorrhea, sinusitis, and otitis.
Infection and infestations: Pyuria, skin infection, tooth infection, varicella, viral infection.
Blood and lymphatic system disorders: Increased bleeding tendency, thrombocytopenia.
Immune system disorders: Hypersensitivity reactions including anaphylaxis.
Psychiatric disorders: Agitation including aggressive behavior or hostility, anxiousness, depression, disorientation, disturbance in attention, dream abnormalities, hallucinations, insomnia, irritability, memory impairment, restlessness, somnambulism, suicidal thinking and behavior (including suicide), tic, tremor.
Nervous system disorders: Dizziness, drowsiness, hyperkinesia, hypoesthesia, paresthesia, seizure.
Eye disorders: Conjunctivitis, myopia.
Ear and labyrinth disorders: Ear pain.
Cardiac disorders: Palpitations.
Vascular disorders: Vasculitis.
Respiratory, thoracic and mediastinal disorders: Acute bronchitis, asthma, Churg-Strauss syndrome, epistaxis, laryngitis, nasal congestion, pneumonia, pulmonary eosinophilia, rhinitis/infective rhinitis, sinus headache, tonsillitis, wheezing.
Gastrointestinal disorders: Dry mouth, dyspepsia, gastroenteritis/infectious gastroenteritis, nausea, pancreatitis, vomiting.
Hepatobiliary disorders: Cholestatic hepatitis, hepatic eosinophilic infiltration, hepatocellular liver injury, mixed-pattern liver injury, increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST).
Skin and subcutaneous tissue disorders: Angioedema, atopic dermatitis, bruising, dermatitis, eczema, erythema multiforme, erythema nodosum, Stevens-Johnson syndrome, pruritus, rash, toxic epidermal necrolysis, 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, dental pain, edema, fatigue, leg pain, malaise, thirst.
Injury, poisoning and procedural complications: Trauma.
Kastair EZ Tab 4 mg: Immune system disorders: Hypersensitivity reactions (including anaphylaxis and angioedema).
Psychiatric disorders: Dream abnormalities (including nightmares), dysphemia (stuttering), obsessive-compulsive symptoms, suicidal thinking and behavior (including completed suicide).

Montelukast may be administered with other drugs routinely used in the prophylaxis and chronic treatment of asthma and in the treatment of allergic rhinitis.
No clinically important effects were observed when montelukast was concomitantly administered with: benzodiazepines, decongestants, digoxin, fexofenadine, itraconazole, nonsteroidal anti-inflammatory agents, oral contraceptives (ethinyl estradiol with norethindrone), prednisone, prednisolone, sedative hypnotics, terfenadine, theophylline, trimethoprim, thyroid hormones, and warfarin.
Kastair EZ Tab 4 mg: Thus, no dosage adjustment is needed when montelukast is coadministered with these medicines.
In addition, montelukast is not anticipated to significantly alter the metabolism of medicines which are metabolized by CYP 2C8 enzyme such as paclitaxel, rosiglitazone, and repaglinide.
Phenobarbital: The area under the plasma concentration-time curve of montelukast decreased by approximately 40% with coadministration of phenobarbital. No dosage adjustment for montelukast is recommended.
Gemfibrozil: Gemfibrozil increased the systemic exposure of montelukast by 4.4-fold in a clinical drug-drug interaction study. No dosage adjustment of montelukast is required upon coadministration with gemfibrozil, but the physician should be aware of the potential for an increase in adverse reactions.
CYP enzyme inducers: Since montelukast is metabolized by CYP 3A4, 2C8, and 2C9, caution should be exercised. Appropriate clinical monitoring should be initiated, particularly in children, when montelukast is coadministered with potent CYP enzyme inducers such as phenobarbital, phenytoin, and rifampicin.
Kastair EZ Tab 5 mg/Kastair: Montelukast-treated patients with known aspirin sensitivity should continue to avoid aspirin and other NSAIDs. Although montelukast can improve airway function in asthmatics with aspirin sensitivity, the drug has not been shown to shorten the bronchoconstrictor response to aspirin or other NSAIDs in such patients.
The area under the plasma concentration-time curve of montelukast decreased by approximately 40% with coadministration of phenobarbital. No dosage adjustment for montelukast is recommended. However, appropriate clinical monitoring should be initiated with concomitant administration of montelukast with potent cytochrome P450 enzyme inducers such as phenobarbital, phenytoin, and rifampicin.

Store at temperatures not exceeding 30°C.
Kastair: 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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