MONTELUKAST SODIUM- montelukast sodium_tablet, film coated

The cysteinyl leukotrienes (LTC 4 4 4 1 1 4 1 Montelukast causes inhibition of airway cysteinyl leukotriene receptors as demonstrated by the ability to inhibit bronchoconstriction due to inhaled LTD 4 4 [see Clinical Studies (14) Montelukast is rapidly absorbed following oral administration. After administration of the 10 mg film-coated tablet to fasted adults, the mean peak montelukast plasma concentration (C max max max max max 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 postdose were minimal in all other tissues. 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. 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 that montelukast and its metabolites are excreted almost exclusively via the bile. Hepatic Insufficiency: max max max [see Adverse Reactions (6. 1) Theophylline, Prednisone, and Prednisolone: in vitro. in vitro In vitro [see Overdosage (10).

Montelukast sodium is a leukotriene receptor antagonist indicated for: Prophylaxis and chronic treatment of asthma in patients 2 years of age and older ( 1. 1 Acute prevention of exercise-induced bronchoconstriction (EIB) in patients 6 years of age and older ( 1. 2 Relief of symptoms of allergic rhinitis (AR): seasonal allergic rhinitis (SAR) in patients 2 years of age and older, and perennial allergic rhinitis (PAR) in patients 2 years of age and older ( 1. 3 Montelukast sodium is indicated for the prophylaxis and chronic treatment of asthma in adults and pediatric patients 2 years of age and older. Montelukast sodium is indicated for prevention of exercise-induced bronchoconstriction (EIB) in patients 6 years of age and older. Montelukast sodium is indicated for the relief of symptoms of seasonal allergic rhinitis in patients 2 years of age and older and perennial allergic rhinitis in patients 2 years of age and older.

Administration (by indications): Asthma ( 2. 1 Acute prevention of EIB ( 2. 2 Seasonal allergic rhinitis ( 2. 3 Perennial allergic rhinitis ( 2. 3 Dosage (by age) (2) 15 years and older: one 10 mg tablet. 6 to 14 years: one 5 mg chewable tablet. 2 to 5 years: one 4 mg chewable tablet. Patients with both asthma and allergic rhinitis should take only one dose daily in the evening ( 2. 4 Montelukast sodium should be taken once daily in the evening. The following doses are recommended: For prevention of EIB, a single dose of montelukast should be taken at least 2 hours before exercise. The following doses are recommended: For allergic rhinitis, montelukast sodium should be taken once daily. Efficacy was demonstrated for seasonal allergic rhinitis when montelukast was administered in the morning or the evening without regard to time of food ingestion. The time of administration may be individualized to suit patient needs. Patients with both asthma and allergic rhinitis should take only one montelukast sodium dose daily in the evening.

Most common adverse reactions (incidence >=5% and greater than placebo listed in descending order of frequency): upper respiratory infection, fever, headache, pharyngitis, cough, abdominal pain, diarrhea, otitis media, influenza, rhinorrhea, sinusitis, otitis ( 6. 1 To report SUSPECTED ADVERSE REACTIONS, contact Lucid Pharma LLC at 1-855-224-6100 or FDA at 1-800-FDA-1088 or www. gov/medwatch Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. In the following description of clinical trials experience, adverse reactions are listed regardless of causality assessment. Adults and Adolescents 15 Years of Age and Older with Asthma TABLE 1: Adverse Experiences Occurring in >=1% of Patients with an Incidence Greater than that in Patients Treated with Placebo Montelukast Placebo * Number of patients tested (montelukast sodium and placebo, respectively): ALT and AST, 1935, 1170; pyuria, 1924, 1159. Body As A Whole Pain, abdominal 2. 5 Asthenia/fatigue 1. 9 Trauma 1 0. 8 Digestive System Disorders Dyspepsia 2. 1 Pain, dental 1. 7 1 Gastroenteritis, infectious 1. 5 Nervous System/Psychiatric Headache 18. 1 Dizziness 1. 4 Respiratory System Disorders Influenza 4. 4 Congestion, nasal 1. 3 Skin/Skin Appendages Disorder Rash 1. 2 Laboratory Adverse Experiences* ALT increased 2. 1 2 AST increased 1. 2 Pyuria 1 0. 9 The frequency of less common adverse events was comparable between montelukast sodium and placebo. Pediatric Patients 6 to 14 Years of Age with Asthma The following adverse reactions have been identified during post-approval use of montelukast sodium. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. [see Warnings and Precautions (5. 4) [see Warnings and Precautions (5.

Hypersensitivity to any component of this product. Hypersensitivity to any component of this product ( 4.

Pregnancy Category B: [see Nonclinical Toxicology (13. 2) 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 sodium is given to a nursing mother. Safety and efficacy of montelukast sodium have been established in adequate and well-controlled studies in pediatric patients with asthma 6 to 14 years of age. Safety and efficacy profiles in this age group are similar to those seen in adults [see Adverse Reactions (6. 1) Clinical Pharmacology, Special Populations (12. 3) Clinical Studies (14. 2) The efficacy of montelukast sodium for the treatment of seasonal allergic rhinitis in pediatric patients 2 to 14 years of age and for the treatment of perennial allergic rhinitis in pediatric patients 2 years to 14 years of age is supported by extrapolation from the demonstrated efficacy in patients 15 years of age and older with allergic rhinitis as well as the assumption that the disease course, pathophysiology and the drug’s effect are substantially similar among these populations. The safety of montelukast chewable tablets 4 mg in pediatric patients 2 to 5 years of age with asthma has been demonstrated by adequate and well-controlled data [see Adverse Reactions (6. 1) The safety of montelukast chewable tablets 4 mg and 5 mg in pediatric patients aged 2 to 14 years with allergic rhinitis is supported by data from studies conducted in pediatric patients aged 2 to 14 years with asthma. A safety study in pediatric patients 2 to 14 years of age with seasonal allergic rhinitis demonstrated a similar safety profile [see Adverse Reactions (6. 1) A 56-week, multi-center, double-blind, randomized, active- and placebo-controlled parallel group study was conducted to assess the effect of montelukast sodium on growth rate in 360 patients with mild asthma, aged 6 to 8 years. Treatment groups included montelukast 5 mg once daily, placebo, and beclomethasone dipropionate administered as 168 mcg twice daily with a spacer device. For each subject, a growth rate was defined as the slope of a linear regression line fit to the height measurements over 56 weeks. The primary comparison was the difference in growth rates between montelukast sodium and placebo groups. Growth rates, expressed as least-squares (LS) mean (95% CI) in cm/year, for the montelukast sodium, placebo, and beclomethasone treatment groups were 5. 08), respectively. The differences in growth rates, expressed as least-squares (LS) mean (95% CI) in cm/year, for montelukast sodium minus placebo, beclomethasone minus placebo, and montelukast sodium minus beclomethasone treatment groups were 0. 09), respectively. Growth rate (expressed as mean change in height over time) for each treatment group is shown in FIGURE 1. FIGURE 1: Change in Height (cm) from Randomization Visit by Scheduled Week (Treatment Group Mean +/- Standard Error* of the Mean) Of the total number of subjects in clinical studies of montelukast, 3. 5% were 65 years of age and over, and 0. 4% were 75 years of age and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. The pharmacokinetic profile and the oral bioavailability of a single 10 mg oral dose of montelukast are similar in elderly and younger adults. The plasma half-life of montelukast is slightly longer in the elderly. No dosage adjustment in the elderly is required. No dosage adjustment is required in patients with mild-to-moderate hepatic insufficiency [see Clinical Pharmacology (12. 3) No dosage adjustment is recommended in patients with renal insufficiency [see Clinical Pharmacology (12.

No dose adjustment is needed when montelukast sodium is co-administered with theophylline, prednisone, prednisolone, oral contraceptives, terfenadine, digoxin, warfarin, gemfibrozil, itraconazole, thyroid hormones, sedative hypnotics, non-steroidal anti-inflammatory agents, benzodiazepines, decongestants, and Cytochrome P450 (CYP) enzyme inducers [see Clinical Pharmacology (12.3)

OVERDOSAGE
No specific information is available on the treatment of overdosage with montelukast sodium. 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 a week without clinically important adverse experiences. In the event of overdose, it is reasonable to employ the usual supportive measures; e.g., remove unabsorbed material from the gastrointestinal tract, employ clinical monitoring, and institute supportive therapy, if required.
NONCLINICAL TOXICOLOGY
No evidence of tumorigenicity was seen in carcinogenicity studies of either 2 years in Sprague-Dawley rats or 92 weeks in mice at oral gavage doses up to 200 mg/kg/day or 100 mg/kg/day, respectively. The estimated exposure in rats was approximately 120 and 75 times the AUC for adults and children, respectively, at the maximum recommended daily oral dose. The estimated exposure in mice was approximately 45 and 25 times the AUC for adults and children, respectively, at the maximum recommended daily oral dose. in vivo Reproductive Toxicology Studies [see Pregnancy (8.
CLINICAL STUDIES
Adults and Adolescents 15 Years of Age and Older with Asthma 1 1 1 1 1 1 The effect of montelukast sodium on other primary and secondary endpoints, represented by the Multinational study is shown in TABLE 2. Results on these endpoints were similar in the U. TABLE 2: Effect of Montelukast Sodium on Primary and Secondary Endpoints in a Multinational Placebo-controlled Trial (ANOVA Model) Montelukast Sodium Placebo Endpoint N Baseline Mean Change from Baseline N Baseline Mean Change from Baseline * p<0. 001, compared with placebo Daytime Asthma Symptoms (0 to 6 scale) 372 2. 26 beta-agonist (puffs per day) 371 5. 42 AM PEFR (L/min) 372 339. 03* 244 335. 83 PM PEFR (L/min) 372 355. 13* 244 354. 49 Nocturnal Awakenings (#/week) 285 5. 78 Both studies evaluated the effect of montelukast sodium on secondary outcomes, including asthma attack (utilization of health-care resources such as an unscheduled visit to a doctor’s office, emergency room, or hospital; or treatment with oral, intravenous, or intramuscular corticosteroid), and use of oral corticosteroids for asthma rescue. In the Multinational study, significantly fewer patients (15. 6% of patients) on montelukast sodium experienced asthma attacks compared with patients on placebo (27. 8% of patients on montelukast sodium and 10. 3% of patients on placebo experienced asthma attacks, but the difference between the two treatment groups was not significant (p = 0. In the Multinational study, significantly fewer patients (14. 8% of patients) on montelukast sodium were prescribed oral corticosteroids for asthma rescue compared with patients on placebo (25. 9% of patients on montelukast sodium and 9. 9% of patients on placebo were prescribed oral corticosteroids for asthma rescue, but the difference between the two treatment groups was not significant (p = 0. Onset of Action and Maintenance of Effects Pediatric Patients 6 to 14 Years of Age with Asthma 1 1 Pediatric Patients 2 to 5 Years of Age with Asthma Effects in Patients on Concomitant Inhaled Corticosteroids 1 1 1 [see Warnings and Precautions (5. 3) FIGURE 2: FEV1 Mean Percent Change from Baseline Exercise-Induced Bronchoconstriction (Adults, Adolescents, and Pediatric Patients 6 years of age and older) 1 TABLE 3: Mean Maximum Percent Fall in FEV 1 Time of exercise challenge Mean Maximum percent fall in 1 Treatment difference % for Montelukast Placebo * Least squares-mean 2 hours 13 22 -9 (-12, -5) 8. 5 hours 12 17 -5 (-9, -2) 24 hours 10 14 -4 (-7, -1) The efficacy of montelukast 5 mg chewable tablets, when given as a single dose 2 hours before exercise for the prevention of EIB, was investigated in one multinational, randomized, double-blind, placebo-controlled crossover study that included a total of 64 pediatric patients 6 to 14 years of age with EIB. Exercise challenge testing was conducted at 2 hours and 24 hours following administration of a single dose of study drug (montelukast 5 mg or placebo). The primary endpoint was the mean maximum percent fall in FEV 1 1 Time of exercise challenge following medication administration Mean Maximum percent fall in FEV 1 Treatment difference % for Montelukast Sodium versus Placebo (95%CI)* Montelukast Sodium Placebo 2 hours 15 20 -5 (-9, -1) 24 hours 13 17 -4 (-7, -1) *Least squares-mean The efficacy of montelukast sodium for prevention of EIB in patients below 6 years of age has not been established. Daily administration of montelukast sodium for the chronic treatment of asthma has not been established to prevent acute episodes of EIB. 1 1 1 1 Seasonal Allergic Rhinitis TABLE 5: Effects of Montelukast Sodium on Daytime Nasal Symptoms Score* in a Placebo- and Active-controlled Trial in Patients with Seasonal Allergic Rhinitis (ANCOVA Model) Treatment Group (N) Baseline Mean Change Difference Between * dagger double dagger Montelukast 10 mg 2. 13 dagger Placebo 2. Active Control double dagger 2. 24 dagger Perennial Allergic Rhinitis TABLE 6: Effects of Montelukast Sodium on Daytime Nasal Symptoms Score* in a Placebo-controlled Trial in Patients with Perennial Allergic Rhinitis (ANCOVA Model) Treatment Group (N) Baseline Mean Mean Change Difference Between Treatment * dagger Montelukast 10 mg (1000) 2. 08 dagger Placebo (980) 2. The other 6-week study evaluated montelukast 10 mg (n=626), placebo (n=609), and an active-control (cetirizine 10 mg; n=120). The primary analysis compared the mean change from baseline in daytime nasal symptoms score for montelukast sodium vs. placebo over the first 4 weeks of treatment; the study was not designed for statistical comparison between montelukast sodium and the active-control. The primary outcome variable included nasal itching in addition to nasal congestion, rhinorrhea, and sneezing. The estimated difference between montelukast sodium and placebo was -0. 04 with a 95% CI of (-0. The estimated difference between the active-control and placebo was -0. 1 with a 95% CI of (-0.
Patient Information
Montelukast Sodium Tablets Montelukast Sodium Chewable Tablets (mon te loo'' kast soe'' dee um) Montelukast sodium is a prescription medicine that blocks substances in the body called leukotrienes. This may help to improve symptoms of asthma and allergic rhinitis. Montelukast sodium does not contain a steroid. Montelukast sodium is used to: Prevent asthma attacks and for the long-term treatment of asthma in adults and children ages 2 years and older. Do not take montelukast sodium if you need relief right away for a sudden asthma attack. Prevent exercise-induced asthma in people 6 years of age and older. Help control the symptoms of allergic rhinitis (sneezing, stuffy nose, runny nose, itching of the nose). Montelukast sodium is used to treat: outdoor allergies that happen part of the year (seasonal allergic rhinitis) in adults and children ages 2 years and older, and indoor allergies that happen all year (perennial allergic rhinitis) in adults and children ages 2 years and older. Who should not take montelukast sodium? Before taking montelukast sodium, tell your healthcare provider if you: are allergic to aspirin have phenylketonuria. Montelukast sodium chewable tablets contain aspartame, a source of phenylalanine have any other medical conditions are pregnant or plan to become pregnant. Talk to your doctor if you are pregnant or plan to become pregnant, as montelukast sodium may not be right for you. are breast-feeding or plan to breast-feed. It is not known if montelukast sodium passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby while taking montelukast sodium. Tell your healthcare provider about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Some medicines may affect how montelukast sodium works, or montelukast sodium may affect how your other medicines work. How should I take montelukast sodium? For anyone who takes montelukast sodium: Take montelukast sodium exactly as prescribed by your healthcare provider. Your healthcare provider will tell you how much montelukast sodium to take, and when to take it. Do not stop taking montelukast sodium or change when you take it without talking with your healthcare provider. You can take montelukast sodium with food or without food. If you or your child misses a dose of montelukast sodium, just take the next dose at your regular time. If you take too much montelukast sodium tablets and/or montelukast sodium chewable tablets, call your healthcare provider or a Poison Control Center right away. For adults and children 2 years of age and older with asthma: Take montelukast sodium 1 time each day, in the evening. Continue to take montelukast sodium every day for as long as your healthcare provider prescribes it, even if you have no asthma symptoms. Tell your healthcare provider right away if your asthma symptoms get worse, or if you need to use your rescue inhaler medicine more often for asthma attacks. Do not take montelukast sodium if you need relief right away from a sudden asthma attack. Always have your rescue inhaler medicine with you for asthma attacks. Do not stop taking or lower the dose of your other asthma medicines unless your healthcare provider tells you to. For patients 6 years of age and older for the prevention of exercise-induced asthma: Take montelukast sodium at least 2 hours before exercise. Always have your rescue inhaler medicine with you for asthma attacks. If you take montelukast sodium every day for chronic asthma or allergic rhinitis, do not Do not take 2 doses of montelukast sodium within 24 hours (1 day). For adults and children 2 years of age and older with seasonal allergic rhinitis, or for adults and children 2 years of age and older with perennial allergic rhinitis: Take montelukast sodium 1 time each day, at about the same time each day. What is the dose of montelukast sodium? 2 to 5 years: one 4 mg chewable tablet. 6 to 14 years: one 5 mg chewable tablet. 15 years and older: one 10 mg tablet. What should I avoid while taking montelukast sodium? What are the possible side effects of montelukast sodium? Montelukast sodium may cause serious side effects. Behavior and mood-related changes. agitation including aggressive behavior or hostility attention problems bad or vivid dreams depression disorientation (confusion) feeling anxious hallucinations (seeing or hearing things that are not really there) irritability memory problems restlessness sleep walking suicidal thoughts and actions (including suicide) tremor trouble sleeping Increase in certain white blood cells (eosinophils) and possible inflamed blood vessels throughout the body (systemic vasculitis). Tell your healthcare provider right away if you get one or more of these symptoms: a feeling of pins and needles or numbness of arms or legs a flu-like illness rash severe inflammation (pain and swelling) of the sinuses (sinusitis) The most common side effects with montelukast sodium include: upper respiratory infection fever headache sore throat cough stomach pain diarrhea earache or ear infection flu runny nose sinus infection Other side effects with montelukast sodium include: increased bleeding tendency, low blood platelet count allergic reactions [including swelling of the face, lips, tongue, and/or throat (which may cause trouble breathing or swallowing), hives and itching] dizziness, drowsiness, pins and needles/numbness, seizures (convulsions or fits) palpitations nose bleed, stuffy nose, swelling (inflammation) of the lungs heartburn, indigestion, inflammation of the pancreas, nausea, stomach or intestinal upset, vomiting hepatitis bruising, rash, severe skin reactions (erythema multiforme, Stevens-Johnson syndrome/toxic epidermal necrolysis) that may occur without warning joint pain, muscle aches and muscle cramps bedwetting in children tiredness, swelling Tell your healthcare provider if you have any side effect that bothers you or that does not go away. These are not all the possible side effects of montelukast sodium. For more information ask your healthcare provider or pharmacist. How should I store montelukast sodium? Store montelukast sodium tablets and montelukast sodium chewable tablets at 20° to 25°C (68° to 77°F). Keep montelukast sodium tablets and montelukast sodium chewable tablets in the container it comes in. Keep montelukast sodium tablets and montelukast sodium chewable tablets in a dry place and away from light. General Information about the safe and effective use of montelukast sodium Keep montelukast sodium and all medicines out of the reach of children. What are the ingredients in montelukast sodium tablets and montelukast sodium chewable tablets? Active ingredient: Inactive ingredients: 4 mg and 5 mg chewable tablet: People with Phenylketonuria: Aurolife Pharma LLC LUCID PHARMA LLC

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MONTELUKAST SODIUM- montelukast sodium_tablet, film coated Product manual source documgent