Aspira

Montelukast.

Pharmacology: Pharmacodynamics: Montelukast is a selective and active leukotriene receptor antagonist. Montelukast inhibits bronchoconstriction due to antigen challenge. Montelukast is a selective leukotriene receptor antagonist of the cysteinyl leukotriene CysLT1 receptor. The cysteinyl leukotrienes (LTC 4, LTD 4, LTE 4) are products of arachidonic acid metabolism that are released from various cells, including mast cells and eosinophils. They bind to cysteinyl leukotriene receptors (CysLT) found in the human airway. Binding of cysteinyl leukotrienes to leukotriene receptors has been correlated with the pathophysiology of asthma, including airway edema, smooth muscle contraction and altered cellular activity associated with the inflammatory process, factors that contribute to the signs and symptoms of asthma.
It binds to CysLT type-1 receptors found in human airway (smooth muscle cells and macrophages), which prevents airway edema, smooth muscle contraction and other respiratory inflammation. The leukotrienes are also released from the nasal mucosa after allergen exposure where montelukast sodium may inhibit symptoms of allergic rhinitis.
Montelukast binding to the CysLT1 receptor is high-affinity and selective, preferring the CysLT1 receptor to other pharmacologically important airway receptors eg, the prostanoid, cholinergic or β-adrenergic receptor. Montelukast inhibits physiologic actions of LTD4 at the CysLT1 receptors, without any agonist activity.
Montelukast causes bronchodilation within 2 hrs of oral administration; these effects were additive to the bronchodilation caused by a β-agonist.
Pharmacokinetics: Absorption: Montelukast is rapidly and nearly completely absorbed following oral administration. Peak plasma concentrations of montelukast occur 3-4 hrs after oral doses. The mean oral bioavailability is 64%. The oral bioavailability and peak plasma concentration (C_max) are not influenced by a standard meal.
Distribution: Montelukast is >99% bound to plasma proteins. The steady-state volume of distribution of montelukast averages 8-11 L. Studies in rats with radiolabeled montelukast indicate minimal distribution across the blood-brain barrier.
Metabolism: Montelukast is extensively metabolized in the liver by cytochrome P-450 isoenzymes CYP3A4 and CYP2C9. Therapeutic plasma concentrations of montelukast do not inhibit cytochromes P-450 3A4, 2C9, 1A2, 2A6, 2C19 or 2D6.
Elimination: The plasma clearance of montelukast averages 45 mL/min in healthy adults. Montelukast and its metabolites are excreted principally in the faeces via the bile.
Elimination Half-Life: 2.7-5 hrs.

Prophylaxis and chronic treatment of asthma in adults and pediatric patients ≥12 months.
Montelukast is indicated in adults and pediatric patients ≥2 years for the relief of daytime and nighttime symptoms of seasonal allergic rhinitis.

Asthma and Allergic Rhinitis: 1 tab daily in the evening.
Asthma and/or Seasonal Allergic Rhinitis: Adults ≥15 years: One 10-mg tablet daily. Children 6-14 years: One 5-mg chewable tablet daily, 2-5 years: One 4-mg chewable tablet or 1 sachet of 4-mg oral granules daily, 12 months-2 years: 1 sachet of 4-mg oral granules daily.
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 1st dose), the patients 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.
Impaired Hepatic Function: No dosage adjustment is required in patients with mild to moderate hepatic insufficiency. There are no clinical data in patients with severe hepatic insufficiency.
Renal Failure: No dosage adjustment is recommended in these patients.
Elderly: No dosage adjustment in the elderly is required.
General Recommendations: The therapeutic effect of montelukast on parameters of asthma control occurs within 1 day. Montelukast tablets, chewable tablets and oral granules can be taken with or without food. 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.
Montelukast is a long-term controller medication which should not be substituted for short acting β-agonists. It is effective alone or in combination with other prophylactic agent. Montelukast is a preventive agent, which should be used in addition to other drugs for the management of asthma.
Administration: Montelukast should be taken once daily. For asthma, the dose should be taken in the evening. For allergic rhinitis, the time of administration may be individualized to suit patient needs.
Oral Granules: Montelukast oral granules can be administered either directly in the mouth, or mixed with a spoonful of cold or room temperature soft food (eg, applesauce) or dissolved in 1 teaspoonful (5 mL) of cold or room temperature baby formula or breast milk. The sachet should not be opened until ready to use. After opening the packet, the full dose of montelukast oral granules must be administered immediately (within 15 mins). If mixed with food or dissolved in baby formula or breast milk, montelukast oral granules must not be stored for future use. Montelukast oral granules are not intended to be dissolved in any liquid other than baby formula or breast milk for administration. However, liquids may be taken subsequent to administration.

Symptoms: Symptoms include abdominal pain, somnolence, thirst, headache, vomiting and psychomotor hyperactivity.
Treatment: Treatment is symptomatic and supportive. Treatment may include removal of unabsorbed material from the gastrointestinal tract, clinical monitoring and supportive therapy if required. It is not known if montelukast can be removed by peritoneal dialysis or hemodialysis.

Hypersensitivity to montelukast or to any component of Aspira.

Aspira chewable tablets are unsuitable for phenylketonurics.

The efficacy of oral montelukast for the treatment of acute asthma attacks has not been established. Therefore, oral montelukast 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 [eg, agitation, aggression, anxiousness, dream abnormalities, hallucinations, depression, disorientation, insomnia, irritability, restlessness, suicidal thinking and behavior (including suicide), tremor] have occurred. 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 physicians if these changes occur.
The reduction in systemic corticosteroids dose in patients receiving antiasthma agents including leukotriene receptor antagonists has been followed in rare cases by the occurrence of ≥1 of the following: Eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy sometimes diagnosed as Churg-Strauss syndrome, a systemic eosinophilic vasculitis.
Although a casual relationship with leukotriene receptor antagonism has not been established, caution and appropriate clinical monitoring are recommended when systemic corticosteroid reduction is considered in patients receiving montelukast.
Patients with known aspirin sensitivity should continue avoidance of aspirin or nonsteroidal anti-inflammatory agents while taking montelukast.
Although montelukast is effective in improving airway function in asthmatics with documented aspirin sensitivity, it has not been shown to truncate bronchoconstrictor response to aspirin and other documented aspirin sensitivity.
Effects on the Ability to Drive or Operate Machinery: Montelukast is not expected to affect a patient's ability to drive a car or operate machinery. However, in very rare cases, individuals have reported drowsiness or dizziness.
Use in pregnancy: The safety and efficacy of montelukast have not been determined in pregnant women. Rarely, congenital limb defects have been reported during post-marketing surveillance; however, causality has not been established. Due to the lack of human safety information, montelukast should be used in pregnant women only if the potential benefit outweighs the potential risk to the fetus.
Use in lactation: Lactation studies with montelukast in humans have not been conducted. Montelukast is excreted into the milk of lactating rats. Until further data are available, caution is advised if montelukast is used in nursing women. Available evidence and/or expert consensus is inconclusive or is inadequate for determining infant risk when used during breastfeeding. Weigh the potential benefits of drug treatment against potential risks before prescribing Aspira during breastfeeding.

Use in pregnancy: The safety and efficacy of montelukast have not been determined in pregnant women. Rarely, congenital limb defects have been reported during post-marketing surveillance; however, causality has not been established. Due to the lack of human safety information, montelukast should be used in pregnant women only if the potential benefit outweighs the potential risk to the fetus.
Use in lactation: Lactation studies with montelukast in humans have not been conducted. Montelukast is excreted into the milk of lactating rats. Until further data are available, caution is advised if montelukast is used in nursing women. Available evidence and/or expert consensus is inconclusive or is inadequate for determining infant risk when used during breastfeeding. Weigh the potential benefits of drug treatment against potential risks before prescribing Aspira during breastfeeding.

Montelukast has been generally well-tolerated. Side effects, which usually were mild, generally did not require discontinuation of therapy.
Cardiovascular Effects: Palpitations, allergic granulomatous angiitis (systemic eosinophilia with vasculitis and a clinical presentation consistent with Churg-Strauss. Symptoms may include eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiac complications and/or neuropathy).
Skin and Subcutaneous Tissue Disorders: Angioedema, bruising, erythema nodosum, atopic dermatitis, eczema, infection of skin and/or SC tissue, rash, urticaria.
Gastrointestinal Effects: Abdominal pain, dental pain, diarrhea, gastroenteritis, indigestion, infection of tooth, nausea, pancreatitis, tonsillitis, vomiting.
Hematologic Effects: Blood coagulation disorder (increased bleeding tendency).
Hepatic Effects: Raised alanine aminotransferase (ALT)/aspartate aminotransferase (AST) levels, cholestatic hepatitis.
Immunologic Effects: Hypersensitivity reactions, including anaphylaxis, varicella and viral infection.
Neurologic Effects: Asthenia, disoriented, dizziness, headache, hyperactive behavior, hypesthesia, insomnia, paresthesia, seizure, sinus headache, drowsiness and tremor.
Ophthalmic Effects: Conjunctivitis, myopia.
Otic Effects: Otalgia, otitis, otitis media.
Psychiatric Effects: Aggressive behavior, agitation, altered behavior, anxiety, depression, dream disorder, feeling nervous, hallucinations, irritability, nightmares, restlessness, sleep disorder, somnambulism; suicidal thinking and behavior (including suicide).
Renal Effects: Pyuria.
Respiratory Effects: Acute bronchitis, cough, epistaxis, laryngitis, nasal congestion and discharge, pharyngitis, pneumonia, respiratory tract infection, rhinitis, sinusitis, upper respiratory infection, wheezing.
Musculoskeletal and Connective Tissue Disorders: Arthralgia, myalgia including muscle cramps.
Others: Fatigue, fever, influenza, malaise, traumatic injury.

Montelukast may be administered with other therapies routinely used in the prophylaxis and chronic treatment of asthma and in the treatment of allergic rhinitis.
Since montelukast is metabolised by CYP3A4, caution should be exercised, particularly in children, when montelukast is co-administered with enzyme inducers of CYP3A4 eg, phenytoin, phenobarbital and rifampicin.
Montelukast is not anticipated to markedly alter the metabolism of medicinal products metabolised by this enzyme (eg, paclitaxel, rosiglitazone, and repaglinide).
Concurrent use of gemfibrozil and montelukast may result in elevated montelukast plasma concentrations.
Concurrent use of prednisone and montelukast may result in severe peripheral edema.
Concurrent use of montelukast and repaglinide may result in increased repaglinide plasma concentrations.

Store below 30°C. Protect from 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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