Montelukast Sodium

Pronunciation: (mon-te-LOO-kast SOE-dee-um)
Class: Leukotriene receptor antagonist

Trade Names

Singulair
- Tablets, oral 10 mg
- Tablets, chewable, oral 4 mg
- Tablets, chewable, oral 5 mg
- Granules 4 mg/packet, oral

Pharmacology

Binds to cysteinyl leukotriene type 1 (CysLT ₁ ) receptor in the upper and lower airways to prevent leukotriene-mediated effects associated with asthma and allergic rhinitis.

Pharmacokinetics

Absorption

Rapidly absorbed. T _max is 3 to 4 h and bioavailability is 64% for 10 mg oral tablet in the fasted state. T _max is 2 to 2.5 h and bioavailability is 73% (63% if taken with food) for the 5 mg chewable tablet. T _max is 2 h for the 4 mg chewable tablet taken without food. The 4 mg granule formulation is bioequivalent to the 4 mg chewable tablet when administered in the fasted state. Administration of granules with a high-fat meal does not affect AUC, but prolongs T _max to 6.4 h and decreases C _max by 35%.

Distribution

Protein binding is more than 99%. Vd is 8 to 11 L.

Metabolism

Extensively metabolized; plasma concentrations of metabolites are undetectable at steady state. CYP-450 3A4 and 2C9 are involved in metabolism.

Elimination

Plasma Cl averages 45 mL/min and mean plasma half-life is 2.7 to 5.5 h; 86% recovered in feces and less than 0.2% in urine.

Special Populations

Renal Function Impairment

Pharmacokinetics were not evaluated in patients with renal impairment.

Hepatic Function Impairment

AUC increased 41% and half-life was prolonged to 7.4 h in patients with mild to moderate hepatic impairment and cirrhosis. Patients with severe hepatic impairment and hepatitis have not been evaluated.

Elderly

Plasma half-life is slightly longer.

Children

In children 6 to 23 mo of age, the systemic exposure to montelukast is higher than in adults.

Gender

Pharmacokinetics are similar in male and female patients.

Race

Differences have not been studied.

Indications and Usage

Prophylaxis and chronic treatment of asthma in patients 12 mo of age and older; relief of symptoms of seasonal allergic rhinitis in patients 2 y of age and older; relief of symptoms of perennial allergic rhinitis in patients 6 mo of age and older; prevention of exercise-induced bronchoconstriction (EIB) in patients 15 y of age and older.

Unlabeled Uses

Atopic dermatitis, chronic urticaria.

Contraindications

Hypersensitivity to any component of the product.

Dosage and Administration

Asthma
Adults and adolescents 15 y of age and older

PO 10 mg daily.

Children 6 to 14 y of age

PO 5 mg daily.

Children 12 mo to 5 y of age

PO 4 mg daily.

EIB
Adults and children 15 y of age and older

PO 10 mg 2 h prior to exercise. An additional dose should not be taken within 24 h of the previous dose.

Perennial Allergic Rhinitis
Adults and adolescents 15 y of age and older

PO 10 mg daily in the evening.

Children 6 to 14 y of age

PO 5 mg once daily in the evening.

Children 6 mo to 5 y of age

PO 4 mg once daily.

Seasonal Allergic Rhinitis
Adults and adolescents 15 y of age and older

PO 10 mg daily.

Children 6 to 14 y of age

PO 5 mg daily.

Children 2 to 5 y of age

PO 4 mg daily.

General Advice

Provide patients with appropriate rescue medication.
Patients taking a daily dose for a particular indication, including chronic asthma, should not take an additional dose to prevent EIB.
Patients with both asthma and allergic rhinitis should take only 1 tablet daily in the evening.

Oral granules
Do not open packet containing granules until ready for use; the full dose must be administered within 15 min of opening packet.
Granules can be administered directly in the mouth, dissolved in 1 teaspoonful (5 mL) of cold or room temperature baby formula or breast milk, or mixed with a spoonful of cold or room temperature soft foods (applesauce, carrots, rice, or ice cream only). If mixing with baby formula, breast milk, or food, do not prepare ahead of time or store for future use. Discard any unused portion.
Do not dissolve granules in any liquid other than baby formula or breast milk for administration; however, liquids can be taken subsequent to administration.

Storage/Stability

Store between 59° and 86°F. Protect from moisture and light.

Drug Interactions

Gemfibrozil

Montelukast plasma concentrations may be elevated, increasing the pharmacologic effects and risk of adverse reactions. Monitor the clinical response and adjust the montelukast dose as needed.

Prednisone

Adverse effects of prednisone (eg, edema) may be increased. Monitor the clinical response. If an interaction is suspected, consider discontinuing one or both agents.

Strong CYP2C9 and CYP3A4 inducers (eg, phenobarbital, rifampin)

May decrease montelukast levels. Monitor the clinical response and adjust the montelukast dose as needed.

Adverse Reactions

Cardiovascular

Cardiac complications, palpitations (postmarketing).

CNS

Headache (18%); asthenia/fatigue, dizziness (2%); abnormal dreams, agitation (including aggressive behavior, hostility, irritability, restlessness, and tremor), anxiousness, depression, disorientation, drowsiness, hallucinations, insomnia, neuropathy, paraesthesia/hypoesthesia, seizures, somnambulism, suicidal thinking and behavior (including suicide) (postmarketing).

Dermatologic

Atopic dermatitis, dermatitis, eczema, rash, skin infection, urticaria (at least 2%); angioedema, bruising, erythema nodosum, pruritus, urticaria, vasculitic rash (postmarketing).

EENT

Conjunctivitis, ear pain, laryngitis, myopia, otitis, pharyngitis, rhinitis, rhinorrhea, sinusitis, tonsillitis (at least 2%); nasal congestion (2%); epistaxis (at least 1%).

GI

Abdominal pain (3%); diarrhea, dyspepsia, gastroenteritis, nausea, tooth infection (at least 2%); dental pain, infectious gastroenteritis (2%); pancreatitis, vomiting (postmarketing).

Hematologic-Lymphatic

Eosinophilia, increased bleeding tendency (postmarketing).

Hepatic

Cholestatic hepatitis, hepatocellular liver injury, mixed-pattern liver injury (postmarketing).

Hypersensitivity

Anaphylaxis, angioedema, hepatic eosinophilic infiltration (postmarketing).

Lab Tests

ALT/AST increased (2%).

Musculoskeletal

Arthralgia, myalgia (including muscle cramps) (postmarketing).

Respiratory

Influenza (4%); cough (3%); acute bronchitis, pneumonia, upper respiratory tract infection, wheezing (at least 2%); sinus headache, cough, epistaxis (at least 1%); worsening of pulmonary symptoms (postmarketing).

Miscellaneous

Fever, varicella, viral infection (at least 2%); pyuria, trauma (1%); edema (postmarketing).

Precautions

Monitor

Monitor patients for mood or behavioral changes, including suicidal thinking and behavior.

Pregnancy

Category B .

Lactation

Undetermined.

Children

Safety and efficacy not established for treatment of EIB in patients younger than 15 y of age. Safety and efficacy not established for treatment of allergic rhinitis in patients younger than 2 y of age. Safety and efficacy not established for treatment of asthma in patients younger than 12 mo of age. Safety and efficacy not established for treatment of perennial allergic rhinitis in patients younger than 6 mo of age.

Acute asthma attacks

Do not use for reversal of bronchospasm in acute asthma attacks, including status asthmaticus.

Aspirin sensitivity

Continue to avoid aspirin or NSAIDs in patients with aspirin sensitivity.

Concurrent corticosteroids

Do not abruptly substitute montelukast for inhaled or oral corticosteroids.

Eosinophilic conditions

Systemic eosinophilia may occur, sometimes presenting with clinical features of vasculitis consistent with Churg-Strauss syndrome.

Exercise-induced asthma

Do not use montelukast as monotherapy for treatment and management of EIB.

Neuropsychiatric events

Carefully evaluate the risk/benefit of continuing treatment if these events occur.

Phenylketonuria

Montelukast chewable tablets contain phenylalanine.

Overdosage

Symptoms

Abdominal pain, headache, psychomotor hyperactivity, somnolence, thirst, vomiting.

Patient Information

Advise patient to read patient information leaflet before using this medicine for the first time and to reread and check for new information with each refill.
Caution patient with asthma not to decrease the dose or stop taking any other asthma medications unless advised by health care provider.
Advise patient that montelukast can be taken without regard to meals, but to take with food if stomach upset occurs.
Advise patient with asthma or asthma and allergic rhinitis to take prescribed dose once daily in the evening.
Advise patient with allergic rhinitis to take prescribed dose once daily at a time that is convenient, but at about the same time each day.
Advise patient or caregiver using granules that the packet containing granules should not be opened until ready for use and that the full dose must be administered within 15 min. Granules can be administered directly in the mouth, dissolved in 1 teaspoonful (5 mL) of cold or room temperature formula or breast milk, or mixed with a spoonful of cold or room temperature soft foods (applesauce, carrots, rice, or ice cream only). Caution patient or caregiver mixing granules with baby formula, breast milk, or food not to prepare ahead of time or store for future use. Instruct patient to discard any unused portion.
Caution patient with asthma that medication is not to be used to treat acute asthma attacks. Instruct patient to always have a short-acting beta-agonist available for acute treatment of asthma symptoms.
Instruct patient to take montelukast every day as prescribed, even when symptoms have been controlled.
Caution patient not to increase montelukast dose or frequency of use, but to notify health care provider if symptoms return or worsen. Caution patients with asthma to notify their health care provider if the need for rescue medication increases or if rescue medication does not seem to work as well.
Advise patients with EIB to use the usual regimen of beta-agonists as prophylaxis unless otherwise instructed by their health care provider.
Advise patient with known aspirin sensitivity to continue avoidance of aspirin and NSAIDs while taking montelukast.
Inform phenylketonuric patients that the chewable tablets contain phenylalanine.
Advise patients to notify their health care provider if neuropsychiatric events (eg, agitation, aggressive behavior, depression, hallucinations, insomnia) occur.