Usage
Montelukast is prescribed for the prophylaxis and chronic treatment of asthma in patients 12 months and older, acute prevention of exercise-induced bronchospasm (EIB) in patients 6 years and older, and relief of symptoms of seasonal allergic rhinitis (SAR) in patients 2 years and older and perennial allergic rhinitis (PAR) in patients 6 months and older. It is classified as a leukotriene receptor antagonist. Montelukast works by blocking the action of leukotrienes, which are substances in the body that cause inflammation and tightening of airway muscles. This helps to prevent asthma symptoms and allergic reactions.
Alternate Names
Montelukast sodium is the chemical name. Singulair is a popular brand name.
How It Works
Pharmacodynamics: Montelukast is a selective and competitive leukotriene receptor antagonist, specifically targeting the CysLT1 receptor. By binding to this receptor, it inhibits the actions of leukotriene D4 (LTD4), a potent bronchoconstrictor and inflammatory mediator. This leads to bronchodilation and reduces airway inflammation, mucus secretion, and vascular permeability, thus alleviating asthma and allergic rhinitis symptoms.
Pharmacokinetics:
- Absorption: Montelukast is rapidly absorbed after oral administration, reaching peak plasma concentrations within 3-4 hours. Food does not significantly affect absorption.
- Metabolism: Montelukast is extensively metabolized in the liver, primarily via cytochrome P450 (CYP) enzymes, mainly CYP3A4 and, to a lesser extent, CYP2C9.
- Elimination: Montelukast and its metabolites are primarily excreted in bile and feces, with minimal renal excretion. The elimination half-life is approximately 2.7-5.5 hours in adults.
Mode of Action: Montelukast competitively binds to the CysLT1 receptor on airway smooth muscle cells and other inflammatory cells, preventing LTD4 from binding and triggering its downstream effects. This includes bronchoconstriction, mucus secretion, and eosinophil recruitment, which are key features of asthma and allergic reactions.
Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: Montelukast selectively and competitively binds to the CysLT1 receptor. It doesn’t directly inhibit enzymes or modulate neurotransmitters.
Dosage
Standard Dosage
Adults: 10 mg orally once daily, usually in the evening for asthma. The timing can be adjusted for allergic rhinitis to suit individual patient needs.
Children:
- 12-23 months: 4 mg oral granules once daily
- 2-5 years: 4 mg chewable tablet or 4 mg oral granules once daily
- 6-14 years: 5 mg chewable tablet once daily
- 15 years and older: 10 mg tablet once daily
Pediatric safety considerations include ensuring the appropriate formulation (chewable tablets or oral granules) is used for younger children and close monitoring for neuropsychiatric events.
Special Cases:
- Elderly Patients: No dosage adjustment is generally required.
- Patients with Renal Impairment: No dosage adjustment is necessary due to minimal renal excretion.
- Patients with Hepatic Dysfunction: Dosage adjustment is usually not required for mild to moderate impairment. Severe hepatic impairment has not been extensively studied, so caution is advised.
- Patients with Comorbid Conditions: For patients with both asthma and allergic rhinitis, a single evening dose is recommended. Consider individual patient needs and potential drug interactions.
Clinical Use Cases
Montelukast is generally not indicated for the acute management of conditions like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations like status epilepticus or cardiac arrest. It focuses on long-term management of asthma and allergic rhinitis. It may be continued during acute asthma exacerbations.
Dosage Adjustments
No specific dosage adjustments are routinely recommended based on renal or hepatic dysfunction, metabolic disorders, or genetic polymorphisms. However, clinical judgment should be exercised in patients with severe hepatic impairment.
Side Effects
Common Side Effects
Headache, upper respiratory tract infection, abdominal pain, diarrhea, fever, cough.
Rare but Serious Side Effects
Churg-Strauss syndrome (a rare type of vasculitis), hepatic dysfunction, neuropsychiatric events (e.g., agitation, aggression, anxiety, depression, hallucinations, insomnia, irritability, restlessness, suicidal ideation), hypersensitivity reactions (e.g., anaphylaxis, angioedema).
Long-Term Effects
The potential long-term effects of montelukast are still being investigated, but some neuropsychiatric symptoms may persist even after discontinuation. Regular monitoring for adverse effects is recommended.
Adverse Drug Reactions (ADR)
Clinically significant ADRs include severe hypersensitivity reactions (anaphylaxis, angioedema), Churg-Strauss syndrome, and severe neuropsychiatric events. These require immediate medical intervention.
Contraindications
Hypersensitivity to montelukast or any of its components.
Drug Interactions
Montelukast is primarily metabolized by CYP3A4 and CYP2C9. Therefore, it can interact with strong inducers or inhibitors of these enzymes. Examples include phenobarbital, rifampin, phenytoin (inducers) and itraconazole, ketoconazole, erythromycin (inhibitors). Gemfibrozil may increase montelukast plasma levels. Monitor for adverse effects and consider dosage adjustments if needed. No significant interactions have been observed with theophylline or warfarin.
Pregnancy and Breastfeeding
Pregnancy Safety Category B. Montelukast should be used during pregnancy only if clearly needed. It’s unknown whether montelukast is excreted in human milk. Caution is advised when administering to breastfeeding mothers.
Drug Profile Summary
- Mechanism of Action: Leukotriene receptor antagonist, blocking the CysLT1 receptor.
- Side Effects: Headache, upper respiratory tract infection, abdominal pain, neuropsychiatric events, hypersensitivity reactions.
- Contraindications: Hypersensitivity.
- Drug Interactions: CYP3A4 and CYP2C9 inducers and inhibitors.
- Pregnancy & Breastfeeding: Category B; caution advised.
- Dosage: Adults: 10 mg once daily; Children: 4-5 mg (2-5 years), 5 mg (6-14 years).
- Monitoring Parameters: Pulmonary function tests, monitor for neuropsychiatric effects, liver function tests if indicated.
Popular Combinations
Montelukast is often used in combination with inhaled corticosteroids (ICS) for asthma management when ICS alone is insufficient. It may also be combined with bronchodilators.
Precautions
- General Precautions: Assess for hypersensitivity, monitor for neuropsychiatric effects.
- Specific Populations: Use with caution during pregnancy and breastfeeding, monitor children closely for neuropsychiatric effects.
- Lifestyle Considerations: No specific lifestyle restrictions are typically necessary.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Montelukast?
A: Adults and adolescents 15 years and older: 10 mg once daily. Children 6-14 years: 5 mg once daily. Children 2-5 years: 4 mg once daily. Infants 6-23 months: 4 mg oral granules once daily.
Q2: When should Montelukast be taken?
A: Usually once daily in the evening for asthma. The timing for allergic rhinitis can be individualized.
Q3: How does Montelukast differ from inhaled corticosteroids (ICS)?
A: Montelukast works by blocking leukotrienes, while ICS reduce airway inflammation through a different mechanism. They can be used together for additive effects.
Q4: Can Montelukast be used to treat acute asthma attacks?
A: No, Montelukast is not a rescue medication for acute attacks. It’s used for long-term control and prevention.
Q5: What are the most common side effects of Montelukast?
A: Common side effects include headache, upper respiratory tract infection, abdominal pain, diarrhea, fever, and cough.
Q6: Are there any serious side effects associated with Montelukast?
A: Yes, rare but serious side effects include Churg-Strauss syndrome, neuropsychiatric events (including suicidal ideation), and hypersensitivity reactions.
Q7: Can pregnant or breastfeeding women take Montelukast?
A: Montelukast is Pregnancy Category B. It should be used during pregnancy only if clearly needed. Caution is advised during breastfeeding.
Q8: Does Montelukast interact with other medications?
A: Yes, it can interact with strong CYP3A4 and CYP2C9 inducers or inhibitors.
Q9: What should I do if a patient experiences neuropsychiatric symptoms while taking Montelukast?
A: Discontinue the medication and consult with a specialist. Carefully evaluate the risks and benefits before resuming treatment.
Q10: How long does it take for Montelukast to start working?
A: The therapeutic effect of montelukast on asthma control can be observed within one day.
