During initial clinical trials, montelukast was evaluated for safety in over 2600 adolescent (>= 15 years) and adult patients and over 1000 pediatric patients <= 14 years, many of whom received the drug for at least one year. Overall, montelukast was well tolerated. The adverse reaction profile of montelukast is generally similar among pediatric and adult patients. Adverse reactions in adults and adolescents > = 15 years with asthma that were reported more frequently in montelukast-treated patients than in placebo-treated patients included asthenia or fatigue (1.8% vs. 1.2%), fever (1.5% vs. 0.9%), trauma (1% vs. 0.8%), abdominal pain (2.9% vs. 2.5%), dyspepsia (2.1% vs. 1.1%), gastritis (1.5% vs. 0.5%), dental pain (1.7% vs. 1%), dizziness (1.9% vs. 1.4%), headache (18.4% vs. 18.1%), influenza (4.2% vs. 3.9%), nasal congestion (1.6% vs. 1.3%), cough (2.7% vs. 2.4%), pyuria (1% vs. 0.9%), and rash (unspecified) (1.6% vs. 1.2%). Other adverse reactions in adults and adolescents > = 15 years with allergic rhinitis that occurred >= 1% and more frequently than placebo included cough, sinusitis, upper respiratory infection (1.9%), sinus headache, and epistaxis. Adverse reactions reported in one or more pediatric study groups (6 months—14 years) that occurred >= 2% and more frequently than placebo include: abdominal pain, atopic dermatitis, cough, diarrhea, dyspepsia, fever, gastroenteritis, laryngitis, pharyngitis, rhinorrhea, nausea, vomiting, otitis, sinusitis, viral infection, conjunctivitis, dermatitis, rash, ear pain, eczema, pneumonia, urticaria, varicella, acute bronchitis, wheezing, tonsillitis, myopia, rhinitis (infective), skin infection, and tooth infection.[29630]

In rare cases, patients on montelukast therapy presented with systemic eosinophilia, sometimes presenting with clinical features of vasculitis consistent with Churg-Strauss syndrome, a systemic eosinophilic vasculitis which is often treated with systemic corticosteroids. These events usually, but not always, have been associated with the reduction of oral corticosteroid therapy. Symptoms include eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy. Patients may initially complain of generalized, flu-like symptoms such as fever, myalgia, and weight loss. Pulmonary eosinophilia has been reported with post-marketing use. Although a causal relationship with leukotriene receptor antagonism has not been established, caution is advised when oral corticosteroid reduction is being considered in patients receiving montelukast.[29630]

During premarketing clinical trials, the incidence of elevated hepatic enzymes during montelukast treatment was not significantly different from patients taking placebo. ALT increased in 2.1% of montelukast-treated patients and 2% of placebo-treated patients; AST increased in 1.6% and 1.2% of patients, respectively. Increased ALT was also reported in >= 1% of patients in a clinical trial of adults and adolescents >= 15 years with perennial allergic rhinitis. According to the manufacturer, there are reports of eosinophilic infiltration of the liver (hypersensitivity hepatitis), and, in post-marketing experience, cholestatic hepatitis, hepatocellular liver-injury, and mixed-pattern liver-injury. Most of the post-marketing events occurred in patients who had underlying potential for liver disease, such as those with a history of alcohol abuse or other forms of hepatitis.[29630]

In post-marketing experience, the following additional adverse reactions have been reported with montelukast: hypersensitivity reactions, including anaphylaxis (anaphylactoid reactions), Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), angioedema, drowsiness, pruritus, erythema nodosum, erythema multiforme, arthralgia, myalgia, muscle cramps, pancreatitis, thrombocytopenia, increased bleeding tendency, bruising (ecchymosis), edema, paresthesias, hypoesthesia, and palpitations.[29630]

Neuropsychiatric events, including changes in mood or behavioral changes, have been reported in adult, adolescent, and pediatric patients taking montelukast. Postmarketing reports include, but are not limited to: agitation, aggressive behavior or hostility, anxiety, depression, disorientation (confusion), attention disturbance, abnormal dreams, dysphemia (stuttering), hallucinations, insomnia, irritability, memory impairment, obsessive-compulsive symptoms (impulse control symptoms), restlessness, somnambulism, suicidal ideation and behavior (including suicide), drowsiness, seizures, tic, and tremor.[29630] Nightmares may be more common in children and typically resolve after drug discontinuation.[56593] In many cases, symptoms resolved after montelukast was discontinued, however, symptoms persisted after discontinuation in some cases. Although neuropsychiatric events were not commonly observed during clinical trials, the clinical details present in some of the postmarketing reports suggest a drug-induced effect, possibly related to the leukotriene pathway. Available data are insufficient to characterize at-risk patients. Advise patients to report changes in behavior and mood; consider alternate therapy if patients develop neuropsychiatric symptoms.[29630] [52011]

Enuresis (night-time urinary incontinence) has been reported in children during post-marketing use of montelukast.[29630]

Montelukast is not effective for the treatment of acute asthma attacks, including status asthmaticus or acute bronchospasm. Thus, patients should be advised to have appropriate rescue medication (e.g., inhaled beta-agonist) available. In addition, according to the manufacturer, montelukast should not be used as monotherapy for the management of exercise-induced bronchospasm. However, montelukast therapy may be continued during the treatment of an acute asthmatic event. Patients should be advised not to stop taking or decrease the use of other asthma treatments when starting montelukast unless otherwise directed by their health care prescriber.

Montelukast is contraindicated for use in those patients with hypersensitivity to any product component. Montelukast chewable tablets should be used with caution in patients with phenylketonuria. Each 4 mg and 5 mg chewable tablet contains 0.674 and 0.842 mg, respectively, of phenylalanine. Before prescribing montelukast chewable tablets to a patient with PKU, consider the combined daily amount of phenylalanine from all sources, including montelukast.[29630]

Behavioral changes consistent with a neuro-psychiatric event have been reported in adult, adolescent, and pediatric patients taking montelukast, and some of these psychiatric and neurologic events appear to be consistent with a drug-related effect.[29630] A Boxed Warning was added to the montelukast prescribing information because of serious neuropsychiatric events and recommended that montelukast only be used to treat allergic rhinitis in patients who are not treated effectively with or cannot tolerate other allergy medicines.[29630] [65079] Postmarketing reports include psychiatric and neurologic events such as agitation, aggressive behavior or hostility, anxiousness, depression, disorientation, disturbance in attention, dream abnormalities, dysphemia (stuttering), hallucinations, insomnia, irritability, memory impairment, obsessive-compulsive symptoms, restlessness, somnambulism, suicidal ideation and behavior (including suicide), tic, and tremor. In many cases, symptoms resolved after montelukast was discontinued, however, symptoms persisted after discontinuation in some cases. Available data are insufficient to characterize at-risk patients. Advise patients and their caregivers to report changes in mood or behavior immediately. Discontinue montelukast immediately if neuropsychiatric systems occur and continue to monitor and provide supportive care until symptoms resolve. Re-evaluate the benefits and risks of restarting montelukast treatment.[29630]

Published data from prospective and retrospective cohort studies of montelukast use during human pregnancy have not established a drug-associated risk of major birth defects. Some of these studies did have limitations including small sample size, retrospective design, and inconsistent comparator groups. In animal reproduction studies, no adverse developmental effects were observed with montelukast administration to pregnant rats and rabbits during organogenesis at oral doses approximately 100 and 110 times, respectively, the maximum recommended human daily oral dose (MRHDOD) based on AUCs.[29630] The National Asthma Education and Prevention Program, Asthma and Pregnancy Working Group list leukotriene receptor antagonists as an alternative treatment option in the recommended stepwise management of asthma in pregnancy. The Working Group states that leukotriene receptor antagonists may be considered for use during pregnancy for patients who had a favorable response prior to becoming pregnant.[45934]

Montelukast may be used during breast-feeding when necessary. Montelukast is present in human milk. However, data available for infants exposed to montelukast either directly (for selected indications) or through breast milk do not suggest a significant risk of adverse effects. Montelukast is approved for use in infants 6 months and older and has been used in newborns in dosages that provide concentrations greater than the amounts in breastmilk. The effects of montelukast on human milk production are unknown. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for montelukast and any potential adverse effects on the breast-fed infant from montelukast or the underlying maternal condition.[29630] The National Asthma Education and Prevention Program, Asthma and Pregnancy Working Group list leukotriene receptor antagonists, such as montelukast, as an alternative treatment option in the recommended stepwise management of asthma in lactating women.[45934]

Safety and effectiveness of montelukast have not been established in neonates and infants < 6 months of age. Montelukast is available in chewable tablets for use in children and oral granules for use in older infants and children.

Montelukast should be used cautiously in patients with hepatic disease. Based on pharmacokinetic studies in mild-moderate stable cirrhosis, the manufacturer has recommended no specific dosage adjustments. However, use caution in patients with severe hepatic impairment, jaundice, or hepatitis. Rarely, in patients with hepatic disease (e.g., from alcoholism or hepatitis), there have been post-marketing reports of cholestatic hepatitis, hepatocellular liver injury, or mixed pattern liver injury.

Caution is advised when oral corticosteroid withdrawal or a reduction in corticosteroid dose is being considered in patients taking montelukast. Although a causal relationship has not been established; in rare cases, reduction in oral corticosteroid dose in patients taking montelukast has resulted in Churg-Strauss syndrome, a systemic eosinophilic vasculitis. Symptoms may include eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy (see Adverse Reactions).

The clearance of montelukast is only slightly decreased in geriatric patients. Dosage reductions in this population are not needed; clinical responses and side effects of montelukast are similar for the elderly as for younger adults.