Montulair 4/Montulair 10

Montelukast.

Each MONTULAIR 10 film coated tablet contains Montelukast Sodium 10.4 mg eq. to Montelukast 10 mg.
Each MONTULAIR 4 ORAL GRANULES packet contains Montelukast Sodium 4.16 mg eq. to Montelukast 4 mg.

Pharmacology: PHARMACODYNAMICS: Montelukast sodium is a selective leukotriene receptor antagonist that inhibits the cysteinyl leukotriene receptor. Cysteinyl leukotrienes and leukotriene receptor occupation have been correlated with the pathophysiology of asthma, including airway edema, smooth muscle contraction, and altered cellular activity associated with the inflammatory process, which contribute to the signs and symptoms of asthma. Cysteinyl leukotrienes are also released from the nasal mucosa following allergen exposure leading to symptoms associated with allergic rhinitis.
PHARMACOKINETICS: Absorption: Tmax, oral, film-coated tablet: 3 hours to 4 hours.
Tmax, oral, granules: 2.3 hours.
Bioavailability: (Film-coated tablet) 64%.
Effect of food: (Granule) Decreases Cmax by 35% and prolonged Tmax to 6.4 hours.
Distribution: Vd: 8 to 11 L.
Protein binding: More than 99%.
Metabolism: Hepatic: Extensively, primarily via CYP 2C8.
Substrate of CYP 2C8, CYP 2C9, and CYP 3A4.
Excretion: Bile: Almost exclusively.
Fecal: 86%.
Renal: Less than 0.2%.
Dialyzable: Unknown (hemodialysis), unknown (peritoneal dialysis).
Plasma clearance: 45 mL/min.
Elimination Half Life: 2.7 to 5.5 hours.
Mild to moderate hepatic impairment: 7.4 hours.

MONTULAIR is indicated in adult and pediatric patients 6 months of age and older 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.
MONTULAIR is indicated for the relief of daytime and nighttime symptoms of allergic rhinitis (seasonal allergic rhinitis in adults and pediatric patients 2 years of age and older, and perennial allergic rhinitis in adults and pediatric patients 6 months of age and older).

MONTULAIR 10: Adult dosing: One 10 mg tablet orally once daily.
Pediatric dosing: 6 to 14 years: 5 mg (half of 10 mg tablet) daily.
15 years and over: one 10 mg tablet daily.
MONTULAIR 4 ORAL GRANULES: Pediatric dosing: 6 months up to 2 years: one packet of 4 mg (as granules) daily.
2 to 5 years: one packet of 4 mg (as granules) daily.
Dose Adjustments: Renal impairment: Dosage adjustment is not recommended.
Hepatic impairment (mild to moderate): Dosage adjustment is not recommended.
Hepatic impairment (severe, or with hepatitis): No specific recommendations are available; has not been evaluated.
Geriatric (65 years or older): Dosage adjustment is not required.
Administration: For asthma, administer the daily dose in the evening, with or without food.
For allergic rhinitis, administer once daily without regard to the time of food ingestion; time of administration can be individualized to suit patient needs.
For exercise-induced bronchoconstriction, administer at least 2 hours before exercise; however, do not take an additional dose within 24 hours of a previous dose.
Granules can be administered either directly in mouth, dissolved in 5 mL of cold or room temperature baby formula or breast milk, or mixed with a spoonful of cold or room-temperature food (applesauce, carrots, rice, or ice cream only). Dose must be administered within 15 minutes of opening packet; discard unused portion.

OVERDOSE AND TREATMENT: In chronic asthma studies, Montelukast was 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 a week without clinically important adverse experiences. In postmarketing experience and clinical studies, most adults and children did not experience any toxicity following Montelukast doses as high as 1000 mg. The most common reported adverse effects were abdominal pain, somnolence, thirst, headache, vomiting, and psychomotor hyperactivity. In a large pediatric case series, Montelukast ingestions of up to 536 mg resulted in minimal or no adverse events. Treatment is symptomatic and supportive.

Hypersensitivity to Montelukast or any component of the formulation.

Concomitant use: Avoid with aspirin or NSAIDs in aspirin-sensitive patients.
Do not abruptly substitute for inhaled or oral corticosteroids, reduce dose of inhaled corticosteroid gradually.
Hematologic: Eosinophilic conditions, including systemic eosinophilia and vasculitis consistent with Churg-Strauss syndrome, have been reported in patients with asthma who are receiving Montelukast. May be associated with reduction of oral corticosteroid therapy.
Psychiatric: Serious neuropsychiatric events have been reported, including suicidal thoughts or completed suicides, and in some cases occurring after discontinuation of therapy, in adult, adolescent, and pediatric patients with and without a previous history of a psychiatric disorder. Alternative therapy should be considered; monitoring required and discontinuation may be required.
Respiratory: Do not use for the reversal of bronchospasm in acute asthma attacks, including status asthmaticus; may continue use with appropriate rescue medication during acute exacerbation of asthma.

Pregnancy: Based on available data, an increased risk of teratogenic effects has not been observed with Montelukast use in pregnancy. Uncontrolled asthma is associated with adverse events on pregnancy (increased risk of perinatal mortality, preeclampsia, preterm birth, low birth weight infants). Poorly controlled asthma or asthma exacerbations may have a greater fetal/maternal risk than what is associated with appropriately used asthma medications. When clinically indicated, treatment with Montelukast should not be withheld during pregnancy.
Breastfeeding considerations: Montelukast is present in breast milk. The decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.
Patients with asthma should be encouraged to breastfeed their infants.

Common: Gastrointestinal: Abdominal pain (2% or greater), Diarrhea (Pediatric, 2% or greater).
Neurologic: Headache (Adult and adolescent, 18.4%; pediatric, 2% or greater).
Otic: Otitis (Pediatric, 2% or greater), Otitis media (Pediatric, 2% or greater).
Respiratory: Cough (1% or greater), Nasal discharge (Pediatric, 2% or greater), Pharyngitis (Pediatric, 2% or greater), Sinusitis (1% or greater), Upper respiratory infection (1% or greater).
Other: Fever (Adult and adolescent, 1.5%; pediatric, 2% or greater), Influenza (Adult and adolescent, 4.2%; pediatric, 2% or greater).
Serious: Cardiovascular: Eosinophilic granulomatosis with polyangiitis.
Neurologic: Disorientated, Disturbance of attention, Insomnia (0.7% to 6%), Memory impairment, Stuttering, Tic, Tremor.
Psychiatric: Aggressive behavior, Agitation, Anxiety (0.14%), Depression (0.15%), Dream disorder, Hallucinations, Irritability (0.27%), Nightmares (0.12%), Obsessive-compulsive disorder, Restlessness (0.11%), Sleep walking disorder, Suicidal behavior, Suicidal thoughts.

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 coadministration 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.

Store below 30°C.

Antiasthmatic & COPD Preparations / Antihistamines & Antiallergics

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

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