Montelukast

586.18

586.18

605-168-4

MHM278SD3E

DTXSID9023334

C66189

R03DC03|R - Respiratory system

95.7

7.9

Solid

1.272±0.06 g/cm3(Predicted)

145-148 °C @ Solvent: Toluene, Methanol

750.5±60.0 °C(Predicted)

407.7±32.9 °C

1.678

8.20e-06 g/L

Commercially available montelukast sodium film-coated and chewable tablets and oral granules should be stored at 25 deg C and protected from light and moisture with exposure for short periods to temperatures of 15-30 deg C permitted. When stored as directed, montelukast sodium film-coated and chewable tablets have an expiration date of 2 years after the date of manufacture.

4.14X10-21 mm Hg at 25 deg C (est)

Henry's Law constant = 1.42X10-20 atm-cu m/mole at 25 °C (est)

243 Ų [M+H]+ [CCS Type: TW, Method: Major Mix IMS/Tof Calibration Kit (Waters)]

Hydroxyl radical reaction rate constant = 1.06X10-14 cu cm/molec-sec at 25 °C (est) /cis isomer/|Hydroxyl radical reaction rate constant = 1.14X10-14 cu cm/molec-sec at 25 °C (est) /trans isomer/|Ozone reaction rate constant = 1.3X10-18 cu cm/molec-sec at 25 °C (est) /cis isomer/|Ozone reaction rate constant = 2.5X10-18 cu cm/molec-sec at 25 °C (est) /trans isomer/

P261, P264, P270, P271, P280, P301+P312, P302+P352, P304+P312, P304+P340, P312, P322, P330, P363, P501

H302

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl Montelukast sodium, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Montelukast sodium/

|Warning|H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]|P261, P264, P270, P271, P280, P301+P312, P302+P352, P304+P312, P304+P340, P312, P322, P330, P363, and P501|Aggregated GHS information provided by 2 companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

The adverse effects associated with overdosage of montelukast include abdominal pain, somnolence, thirst, headache, vomiting, psychomotor hyperactivity, and less frequently, convulsion. The oral LD50 value determined for mice and rats is >5000 mg/kg. Montelukast has not been studied in pregnant women. Consequently, it should be used during pregnancy only if clearly needed. Additionally, as it is unknown whether montelukast is excreted into human breast milk, there is also caution regarding the use of the medication in nursing mothers. The plasma half-life of montelukast is somewhat prolonged in elderly patients, although no dosage adjustment is generally necessary.

In clinical trials, mild elevations in serum aminotransferase levels were found in 1% to 2% of patients taking montelukast chronically, but similar rates are reported in matched placebo recipients. The ALT abnormalities were usually mild, asymptomatic and self limited. Clinically apparent liver injury from montelukast is rare; but more than a dozen cases reported in the literature. In these cases, the latency to onset of injury was highly variable, ranging from a few days to several years. Patients presented with anorexia, nausea, right upper quadrant pain, dark urine, and jaundice. The pattern of enzyme elevation was usually mixed, but both hepatocellular or cholestatic patterns have been reported. Allergic features and autoantibody formation were rare. Eosinophilia was often reported, but this may have been due to the underlying allergic condition rather than the liver injury. The injury usually resolved within 1 to 4 months of stopping the drug.

Concurrent use /of phenobarbital/ results in significant decreases (approximately 40%) in the area under the curve [AUC] for montelukast, of induction of hepatic metabolism...|... This study was designed to evaluate whether montelukast at clinically used dosage levels would interfere with the anticoagulant effect of warfarin. In a two-period, double-blind, randomized crossover study, 12 healthy male subjects received a single oral dose of 30 mg warfarin on the 7th day of a 12-day treatment with montelukast, 10 mg daily by mouth, or a placebo. Montelukast had no significant effect on the area under the plasma concentration-time curves and peak plasma concentrations of either R- or S-warfarin. However, slight but statistically significant decreases in time to peak concentration of both warfarin enantiomers and in elimination half-life of the less potent R-warfarin were observed in the presence of montelukast. These changes were not considered as clinically relevant. Montelukast had no significant effect on the anticoagulant effect of warfarin, as assessed by the international normalized ratio (INR) for prothrombin time (AUC0-144 and INR maximum). The results of this study suggest that a clinically important interaction between these drugs is unlikely to occur in patients requiring concomitant administration of both drugs.|The effect of montelukast (MK-0476), a cysteinyl leukotriene receptor antagonist, ... on single-dose theophylline plasma concentrations was studied in three separate clinical trials. Montelukast was evaluated at 10 mg once daily (the clinical dosage), 200 mg once daily, and 600 mg (200 mg three times daily). At the clinical dosage, montelukast did not change single-dose theophylline plasma concentration in a clinically important manner. The geometric mean ratios for theophylline area under the plasma concentration versus time curve (AUC0-->infinity ) (0.92) and maximal plasma concentration (Cmax ) (1.04) were well within the predefined and generally accepted bioequivalence range of 0.80 and 1.25. Montelukast decreased theophylline Cmax by 12% and 10%, AUC0-->infinity by 43% and 44%, and elimination half-time by 44% and 39% at 200 mg/d (oral and intravenous, respectively), and at 600 mg/d, montelukast decreased theophylline Cmax by 25%, AUC0-->infinity by 66%, and elimination half-time by 63%. These results show that montelukast at the clinical dosage did not change theophylline pharmacokinetics in a clinically important manner, but at 20- to 60-fold higher dosages, montelukast significantly reduced the theophylline pharmacokinetics parameters; an apparent dosage dependence is suggested.|High aminotransferases and prolonged prothrombin time on entering our liver unit were revealing parenchymal collapse for this 45-year-old obese woman; treatment failure led her to death. Autoimmunity, paracetamol use, alcoholism, and Wilson's disease were all excluded as causes. Because of chronic asthma, she had been receiving a leukotriene receptor antagonist (montelukast) for 5 years before the current presentation; 1 week before onset she had had 1 week of treatment with two dietary supplements for weight control; one of these included Garcinia Cambogia, a possible cause of two recent cases of hepatitis in the USA; in addition, both formulas contained a citrus derivative that interferes cytochrome functions. /The authors/ speculate on a causal relationship between the assumption of the additives and the fatal hepatitis and envisage a synergy between the additives and montelukast, which per se has well been studied as a hepatotoxic drug. Despite the speculative nature of this presentation, /investigators/ believe the warning may serve to focus attention on the uncontrolled escalation of food additives going on /at present/.|... The present case describes an asthmatic patient, who developed severe obstructive symptoms and progressive heart failure after two sequential exposures to montelukast. As the patient exhibited a markedly raised blood eosinophil count with diffuse infiltrates on chest x-ray and signs of myocarditis, Churg-Strauss syndrome (CSS) was suspected. The disease was confirmed by open lung biopsy. The symptoms improved rapidly after administration of high dose immunosuppression with methylprednisolone and cyclophosphamide. This case is noteworthy because the time course of events strongly suggests a direct aetiological role for montelukast in the development of CSS. The pathophysiological mechanism of the association remains unknown.

It has been determined that the protein binding of montelukast to plasma proteins exceeds 99%.

Montelukast's production and use as an antiasthmatic(1) may result in its release to the environment through various waste streams(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 6.0X10+7(SRC), determined from a structure estimation method(2), indicates that montelukast is expected to be immobile in soil(SRC). The estimated pKa of montelukast is 4.3(3), indicating that this compound will primarily exist in the anion form in the environment and anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Volatilization of montelukast from moist soil surfaces is not expected to be an important fate process(SRC) based upon the estimated pKa(3). Montelukast is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 4.1X10-21 mm Hg(SRC), determined from a fragment constant method(5). Biodegradation data for montelukast were not available(SRC, 2008).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 6.0X10+7(SRC), determined from a structure estimation method(2), indicates that montelukast is expected to adsorb to suspended solids and sediment(SRC). An estimated pKa of 4.3(3) indicates montelukast will exist almost entirely in the anion form at pH values of 5 to 9 and therefore volatilization from water surfaces is not expected to be an important fate process(4). According to a classification scheme(5), an estimated BCF of 3.2(SRC), from an estimated log Kow of 9.5(6) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data for montelukast were not available(SRC, 2008).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), montelukast, which has an estimated vapor pressure of 4.1X10-21 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase montelukast may be removed from the air by wet or dry deposition(SRC). Montelukast contains chromophores that absorb at wavelengths >290 nm(3) and therefore may be susceptible to direct photolysis by sunlight(SRC).

Montelukast is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(1). Montelukast contains chromophores that absorb at wavelengths >290 nm(1) and therefore may be susceptible to direct photolysis by sunlight(SRC).

An estimated BCF of 3.2 was calculated for montelukast(SRC), using an estimated log Kow of 9.5(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of montelukast can be estimated to be 6.0X10+7(SRC). According to a classification scheme(2), this estimated Koc value suggests that montelukast is expected to be immobile in soil. The estimated pKa of montelukast is 4.3(3), indicating that this compound will primarily exist in the anion form in the environment and anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4).

An estimated pKa of 4.3(1) indicates montelukast will exist almost entirely in the anion form at pH values of 5 to 9 and therefore volatilization from water surfaces or moist soil is not expected to be an important fate process(2). Montelukast is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 4.1X10-21 mm Hg(SRC), determined from a fragment constant method(3).

While data specific to montelukast were not located(SRC, 2008), the literature suggests that some pharmaceutically active compounds originating from human and veterinary therapy are not eliminated completely in municipal sewage treatment plants and are therefore discharged into receiving waters(1). Wastewater treatment processes often were not designed to remove them from the effluent(2). Selected organic waste compounds may be degrading to new and more persistent compounds that may be released instead of or in addition to the parent compound(2). Studies have indicated that several polar pharmaceutically active compounds can leach through subsoils into aquifers(1).

Occupational exposure to montelukast may occur through dermal contact with this compound at workplaces where montelukast is produced or used. Exposure to montelukast among the general population may be limited to those administered the drug (Singulair), an antiasthmatic agent. (SRC)

Montelukast is indicated for: (a) the prophylaxis and chronic treatment of asthma in adults and pediatric patients who are 12 months of age and older, although other regional health authorities specifically note this indication for adults and adolescents who are 15 years and older and also include indications for preventing day and night-time symptoms, and the treatment of acetylsalicylic acid-sensitive asthma; (b) the prevention of exercise-induced bronchoconstriction (EIB) in patients who are 6 years of age and older, although other regional health authorities specifically note this indication for adults and adolescents who are 15 years and older; and (c) the relief of symptoms of seasonal allergic rhinitis in patients 2 years of age and older and perennial allergic rhinitis in patients 6 months of age and older, although other regional health authorities specifically note the relief of seasonal allergic rhinitis symptoms for adults and adolescents who are 15 years and older. Furthermore, some formulations like chewable montelukast tablets may also be specifically indicated by particular regulatory bodies for the prophylaxis and chronic treatment of asthma, including the prevention of day and night-time symptoms, the treatment of acetylsalicylic acid based asthma, and the prevention of exercise-induced bronchoconstriction in adult and pediatric patients aged 2 and older, between the ages 2 and 5, or between the ages of 6 and 14 years. Moreover, when employed for such indications montelukast is considered effective as monotherapy or when combined with other medications indicated for the maintenance treatment of chronic asthma. For instance, montelukast and inhaled corticosteroids can be used concomitantly to demonstrate additive effects to control asthma or to decrease the necessary inhaled corticosteroid dose while still maintaining clinical stability. Additionally, in patients who continue to experience asthma symptoms, montelukast can also be combined with an 'as required' short-acting beta-agonist, an inhaled corticosteroid, or inhaled corticosteroid paired with a long-acting beta-agonist.|FDA Label|Treatment of allergic rhinitis

Montelukast is an orally available leukotriene receptor antagonist which is widely used for the prophylaxis and chronic treatment of asthma and has been linked to rare cases of clinically apparent liver injury.

Antiasthma Agents

Anti-Asthmatic agents; Leukotriene Antagonists|Montelukast is indicated for prophylaxis and chronic treatment of asthma in adults and pediatric patients 12 months of age and older. /Included in US product label/|Montelukast is indicated for the relief of symptoms of seasonal allergic rhinitis in adults and pediatric patients 2 years of age and older. /Included in US product label/|Montelukast is not indicated for treatment of bronchospasm in acute asthma attacks, including status asthmaticus. /Not included in US product label/

Headache is the most frequently reported adverse effect with montelukast, occurring in 18-19% of children 6 years of age or older, adolescents, and adults. Headache has been reported in at least 2% of children 2-8 years of age with asthma receiving montelukast and in at least 1% (and more frequently than with placebo) of adults and adolescents 15 years of age or older with asthma. Sinus headache has been reported in at least 1% of adult and adolescent patients 15 years of age or older with perennial allergic rhinitis receiving montelukast and more frequently than in those receiving placebo. Dizziness or asthenia/fatigue has occurred in about 1.8-1.9% of patients 15 years of age or older receiving the drug in clinical studies. Dream abnormalities, hallucinations, agitation including aggressive behavior, paresthesia/hypoesthesia, drowsiness, insomnia, irritability, or restlessness also has been reported; seizures have been reported very rarely.|Abdominal pain has occurred in 2.9% of patients 15 years of age or older receiving montelukast. Dyspepsia, infectious gastroenteritis, and dental pain have been reported in 2.1, 1.5, and 1.7% of patients in this age group, respectively. Diarrhea or nausea has been reported in at least 2% of children 6-14 years of age receiving montelukast. Abdominal pain, diarrhea, and gastroenteritis has been reported in at least 2% of children 2-5 years of age with asthma and more frequently than in those receiving placebo. Gastroenteritis has been reported in at least 2% of children 6-8 years of age with asthma and more frequently than in those receiving placebo. Nausea, vomiting, dyspepsia, pancreatitis (rarely), and diarrhea also have been reported with montelukast therapy during postmarketing experience.|Elevations in the results of one or more liver function tests have occurred in patients receiving montelukast in clinical studies. Increases in serum ALT (SGPT) or AST (SGOT) concentrations occurred in 2.1 or 1.6%, respectively, of patients 15 years of age or older with asthma receiving montelukast in clinical studies. Increases in ALT occurred in at least 1% of adult and adolescent patients 15 years of age or older with perennial allergic rhinitis receiving montelukast in clinical studies and more frequently than in those receiving placebo. Changes in laboratory values returned to normal despite continuing montelukast therapy or were not directly attributable to drug therapy. Elevations in serum aminotransferase (transaminase) concentrations also have been reported in children 2-14 years of age receiving montelukast, but the incidence of these elevations was similar to that in children receiving placebo. Hepatic eosinophilic infiltration has been reported very rarely through postmarketing experience with montelukast. Hepatocellular injury, cholestatic hepatitis, or mixed-pattern liver injury also has been reported rarely through postmarketing experience with montelukast. Confounding factors were present in most of these patients, such as the concomitant use of other drugs or alcohol or in the presence of coexisting conditions (e.g., other forms of hepatitis).|Rash has occurred in 1.6% of adults and adolescents 15 years of age or older receiving montelukast. Rash, eczema, dermatitis, or urticaria has been reported in at least 2% of children 2-5 years of age receiving the drug. Atopic dermatitis, varicella, and skin infection have been reported in at least 2% of children 6-8 years of age with asthma receiving montelukast and more frequently than in those receiving placebo. Hypersensitivity reactions, including anaphylaxis, angioedema, pruritus, urticaria, and rarely hepatic eosinophilic infiltration, have been reported in patients receiving montelukast.|For more Drug Warnings (Complete) data for MONTELUKAST (17 total), please visit the HSDB record page.

Montelukast is a leukotriene receptor antagonist that demonstrates a marked affinity and selectivity to the cysteinyl leukotriene receptor type-1 in preference to many other crucial airway receptors like the prostanoid, cholinergic, or beta-adrenergic receptors. As a consequence, the agent can elicit substantial blockage of LTD4 leukotriene-mediated bronchoconstriction with doses as low as 5 mg. Moreover, a placebo-controlled, crossover study (n=12) demonstrated that montelukast is capable of inhibiting early and late phase bronchoconstriction caused by antigen challenge by 75% and 57% respectively. In particular, it has been documented that montelukast can cause bronchodilation as soon as within 2 hours of oral administration. This action can also be additive to the bronchodilation caused by the concomitant use of a beta agonist. Nevertheless, clinical investigations performed with adults 15 years of age and older revealed that no additional clinical benefit is obtained when doses of montelukast greater than 10 mg a day are used. Additionally, in clinical trials with adults and pediatric asthmatic patients aged 6 to 14 years, it was also determined that montelukast can reduce mean peripheral blood eosinophils by about 13% to 15% from baseline in comparison to placebo during double-blind treatment periods. At the same time, in patients aged 15 years and older who were experiencing seasonal allergic rhinitis, the use of montelukast caused a median reduction of 13% in peripheral blood eosinophil counts when compared to placebo as well.

Drugs that are used to treat asthma. (See all compounds classified as Anti-Asthmatic Agents.)|Drugs and compounds that induce the synthesis of CYTOCHROME P-450 CYP1A2. (See all compounds classified as Cytochrome P-450 CYP1A2 Inducers.)|A class of drugs designed to prevent leukotriene synthesis or activity by blocking binding at the receptor level. (See all compounds classified as Leukotriene Antagonists.)

It has been observed that montelukast is quickly absorbed following administration by the oral route. The oral bioavailability documented for the drug is 64%. Furthermore, it seems that having a regular meal in the morning or even a high fat snack in the evening does not affect the absorption of montelukast.|It has been reported that montelukast and its metabolites are almost exclusively excreted in the bile and into the feces.|The steady-state volume of distribution recorded for montelukast is an average between 8 to 11 litres.|The plasma clearance documented for montelukast is an average of 45 mL/min when observed in healthy adults.|Montelukast is rapidly absorbed from the GI tract, and peak plasma concentrations are attained within 3-4, 2-2.5, or 2 hours following oral administration in the fasted state of a single 10-mg film-coated (in adults), 5-mg chewable (in adults), or 4-mg chewable (in children 2-5 years of age) tablet, respectively. ... Ingestion of a high-fat meal in the morning with the 4-mg oral granules formulation had no effect on the AUC of montelukast; however, the time to peak plasma concentrations was prolonged from 2.3 hours to 6.4 hours and peak plasma concentrations were reduced by 35%.|Absorption /of montelukast is/ rapid. For the 10-mg tablets: mean oral bioavailability is 64%. Bioavailability is not affected by a standard meal in the morning. For the 5-mg chewable tablet: mean oral bioavailability is 73% in the fasted state versus 63% when administered with a standard meal in the morning.|Following oral administration of montelukast 10 mg daily for 7 days in fasting young adults, peak plasma concentrations averaged 541 ng/mL on day 1 and 602.8 ng/mL on day 7. Trough concentrations on days 3-7 were essentially constant and ranged from 18-24 ng/mL. In this study, values for area under the plasma concentration-time curve (AUC) at steady-state were about 14-15% higher than those achieved with a single dose, and were reached within 2 days.|The pharmacokinetics of montelukast are nearly linear at doses of up to 50 mg.|For more Absorption, Distribution and Excretion (Complete) data for MONTELUKAST (15 total), please visit the HSDB record page.

It has been determined that montelukast is highly metabolized and typically so by the cytochrome P450 3A4, 2C8, and 2C9 isoenzymes. In particular, it seems that the CYP2C8 enzymes play a significant role in the metabolism of the drug. Nevertheless, at therapeutic doses, the plasma concentrations of montelukast metabolites are undetectable at steady state in adults and pediatric patients.|Biotransformation /is/ hepatic and extensive involving cytochrome P450 3A4 and 2C9|The metabolic fate of montelukast has not been fully determined, but the drug is extensively metabolized in the GI tract and/or liver and excreted in bile. Several metabolic pathways have been identified including acyl glucuronidation, and oxidation catalyzed by several cytochrome P-450 (CYP) isoenzymes. In vitro studies indicate that the microsomal P-450 isoenzyme CYP3A4 is the major enzyme involved in formation of the 21-hydroxy metabolite (M5) and a sulfoxide metabolite (M2), and CYP2C9 is the major isoenzyme involved in the formation of the 36-hydroxy metabolite (M6). Other identified metabolites include an acyl glucuronide (M1) and a 25-hydroxy (a phenol, M3) analog.|Following oral administration of 54.8 mg of radiolabeled montelukast, metabolites of the drug represented less than 2% of circulating radioactivity. Montelukast metabolites that have been identified in plasma in radiolabeled studies include the 21-hydroxy (diastereomers of a benzylic acid, M5a and M5b) and the 36-hydroxy (diastereomers of a methyl alcohol, M6a and M6b) metabolites. Following oral administration of therapeutic doses of montelukast, plasma concentrations of metabolites at steady-state in adults and children were below the level of detection.|Montelukast has known human metabolites that include 21(S)-Hydroxy Montelukast, 21-Hydroxymontelukast, Montelukast 1, 2-Diol, and montelukast sulfoxide.

Studies have demonstrated that the mean plasma half-life of montelukast varies from 2.7 to 5.5 hours when observed in healthy young adults.|The mean plasma elimination half-life of montelukast in adults 19-48 years of age is 2.7-5.5 hours, and plasma clearance averages 45 mL/minute. A plasma elimination half-life of 3.4-4.2 hours has been reported in children 6-14 years of age. Limited data indicate that the plasma elimination half-life of montelukast is prolonged slightly in geriatric adults and in patients with mild to moderate hepatic impairment, although dosage adjustment is not required. A plasma elimination half-life of 6.6 or 7.4 hours has been reported in geriatric adults 65-73 years of age or patients with mild to moderate hepatic impairment, respectively.

Cysteinyl leukotrienes (CysLT) like LTC4, LTD4, and LTE4, among others, are eicosanoids released by a variety of cells like mast cells and eosinophils. When such CysLT bind to corresponding CysLT receptors like CysLT type-1 receptors located on respiratory airway smooth muscle cells, airway macrophages, and on various pro-inflammatory cells like eosinophils and some specific myeloid stem cells activities that facilitate the pathophysiology of asthma and allergic rhinitis are stimulated. In particular, CysLT-mediated airway bronchoconstriction, occluding mucous secretion, vascular permeability, and eosinophil recruitment are all types of effects that facilitate asthma. Alternatively, in allergic rhinitis, CysLTs are released by the nasal mucosa when exposed to allergens during both early and late phase reactions and participate in eliciting symptoms of allergic rhinitis like a congested nose and airway. Subsequently, montelukast is a leukotriene receptor antagonist that binds with high affinity and selectivity to the CysLT type 1 receptor, which consequently assists in inhibiting any physiological actions of CysLTs like LTC4, LTD4, and LTE4 at the receptor that may facilitate asthma or allergic rhinitis.|Montelukast inhibits bronchoconstriction due to antigen challenge. Montelukast is a selective leukotriene receptor antagonist of the cysteinyl leukotriene CysLT1 receptor. The cysteinyl leukotrienes (LTC4 , LTD4, LTE4) 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. Montelukast binding to the CysLT1, receptor is high-affinity and selective, preferring the CysLT1 receptor to other pharmacologically important airway receptors, such as the prostanoid, cholinergic, or beta-adrenergic receptor. Montelukcast inhibits physiologic actions of LTD4 at the CysLT1 receptors, without any agonist activity.|Because of the role of leukotrienes in the pathogenesis of asthma, modification of leukotriene activity may be used to reduce airway symptoms, decrease bronchial smooth muscle tone, and improve asthma control. Inhibition of leukotriene-mediated effects may be achieved by drugs that interrupt 5-lipoxygenase activity and prevent formation of leukotrienes (e.g., zileuton) or by antagonism of leukotriene activity at specific receptor sites in the airway (e.g., montelukast, zafirlukast). The antagonist activity of montelukast is selective, competitive, and reversible. Montelukast competitively inhibits the action of LTD4 at a subgroup of CysLT receptors (CysLT1) in airway smooth muscle. In vitro, montelukast possesses affinity for the CysLT1 receptor that is similar to that of LTD4. In in vitro studies, montelukast antagonized contraction of isolated animal smooth muscle produced by LTD4, but did not antagonize contraction produced by LTC4. In animal studies, montelukast antagonized contraction of airway smooth muscle produced by LTD4 or antigen.

/SIGNS AND SYMPTOMS/ There have been reports of acute overdosage with Montelukast doses of up to 1 g in adults and children. While adverse effects were not reported in most incidents of overdosage, the most frequently reported adverse experiences that were reported included abdominal pain, somnolence, thirst, headache, vomiting, and psychomotor hyperactivity. Clinical and laboratory findings associated with these reports were consistent with the safety profile of the drug in adults and pediatric patients.|/CASE REPORTS/ The case history is presented of a man with allergic rhinitis and asthma who had received intermittent pulse therapy with oral corticosteroids. Pulmonary eosinophilia developed while he was receiving treatment with montelukast, a chemically distinct cysteinyl leukotriene type 1 receptor antagonist. After discontinuation of montelukast therapy and administration of systemic corticosteroids the patient's symptoms reversed rapidly and there was prompt resolution of the pulmonary infiltrates. /Investigators/ believe that cysteinyl leukotriene type 1 receptor antagonists are safe and effective drugs for most patients with asthma but caution is needed for those with more severe disease who require systemic corticosteroids, especially if they show characteristics of the atypical allergic diathesis seen in the prodromal phase of Churg-Strauss syndrome.|/CASE REPORTS/ A 68-year-old asthmatic presented markedly unwell with arthralgia, mononeuritis multiplex, peripheral neuropathy, and eosinophilia. His past medical history included perennial rhinitis, and nasal polyps. Three months prior to admission his prednisolone was stopped and Montelukast was started. The diagnosis of Montelukast-associated Churg-Strauss syndrome was made. The drug was stopped and steroids started with general improvement and reduction of eosinophilia; however, the neurological deficit persisted.|/CASE REPORTS/ ... A 28-year-old man with allergic rhinitis and moderate persistent asthma developed generalized urticaria 5 days after the initiation of montelukast and inhaled fluticasone. Symptoms disappeared within one day after suspension of both drugs. Two months later, after the resumption of montelukast and fluticasone, the patient developed generalized urticaria and eyelid angioedema, which were successfully treated with intravenous betamethasone, achieving complete remission within hours. After 2 days, the patient resumed inhaled fluticasone only and continued this therapy for several months without any adverse reaction. /Investigators/ attributed the adverse reaction to montelukast because of the temporal relationship between use of montelukast and urticaria, the absence of other identified causative factors and other explanations for allergic reactions, and the positive dechallenge and rechallenge. The Naranjo probability scale showed a probable relationship between skin manifestations and montelukast treatment. ...|For more Human Toxicity Excerpts (Complete) data for MONTELUKAST (9 total), please visit the HSDB record page.

1-((((1R)-1-(3-((E)-2-(7-chloro-2-quinolinyl)ethenyl)phenyl)-3-(2-(1-hydroxy-1-methylethyl)phenyl)propyl)thio)methyl)-cyclopropaneacetic acid

Montelukast oral formulations: Granules 4 mg (of Montelukast) Singulair, Merck; Tablets, chewable 4 and 5 mg (of Montelukast) Singulair, Merck; Tablets, film-coated 10 mg (of Montelukast) Singulair, Merck

Montelukast sodium, the active ingredient in Singulair, is a selective and orally active leukotriene receptor antagonist that inhibits the cysteinyl leukotrience CysLT, receptor. /Montelukast sodium/

Analyte: monteleukast; matrix: bile, blood (plasma); procedure: high-performance liquid chromatography with tandem mass spectrometry detection|Analyte: monteleukast; matrix: blood (plasma); procedure: high-performance liquid chromatography with fluorescence detection at 350 nm (excitation) and 400 nm (emission)|Analyte: monteleukast; matrix: blood (plasma); procedure: high-performance liquid chromatography with fluorescence detection at 350 nm (excitation) and 400 nm (emission); limit of detection 9.6 ng/mL

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