What is the incidence of headache as an adverse effect of Singulair (montelukast)?

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Headache Incidence with Singulair (Montelukast)

Based on FDA-approved labeling data, headache occurs in approximately 18.4% of adult patients taking Singulair (montelukast) 10 mg daily, compared to 18.1% with placebo—representing no clinically significant difference from placebo rates. 1

Adult and Adolescent Patients (≥15 Years)

The FDA prescribing information provides the most definitive data for headache incidence:

  • Headache occurred in 18.4% of patients receiving montelukast 10 mg/day in placebo-controlled trials 1
  • Placebo group experienced headache in 18.1% of cases 1
  • This minimal difference (0.3%) indicates headache is not attributable to the medication itself but rather reflects the baseline rate in the asthma population 1

The FDA data represents 1,955 patients treated with montelukast in controlled clinical trials, providing robust statistical power for this assessment. 1

Pediatric Populations

Children 6-14 Years of Age

  • Headache occurred at a rate ≥2% and more frequently than placebo in some pediatric studies, though specific percentages are not provided in the FDA labeling 1
  • The American Academy of Allergy, Asthma, and Immunology confirms that headache is a common side effect in pediatric patients 2

Children 2-5 Years of Age

  • Headache was reported with a frequency ≥2% and more frequently than placebo 1
  • The overall safety profile remained similar to older age groups 1

Long-Term Safety Data

Comprehensive pooled analyses demonstrate consistent findings:

  • In 2,031 adult patients treated for up to 4.1 years, headache incidence remained similar to placebo throughout the treatment duration 3
  • Analysis of 3,386 adult patients showed no clinically relevant differences in headache rates between montelukast and placebo groups 3
  • The most common adverse effect in pediatric studies was headache, but at rates not statistically significantly different from placebo 4

Clinical Context and Interpretation

The key clinical takeaway is that while headache is commonly reported (approximately 1 in 5 patients), it occurs at essentially the same rate whether patients take montelukast or placebo. 1 This suggests that headaches in these patients are more likely related to:

  • The underlying asthma or allergic condition itself 1
  • Concurrent respiratory infections 1
  • Other comorbid factors 3

Rather than being caused by the medication.

Important Safety Considerations

While headache itself is not a medication-related concern, the FDA issued a black box warning in 2020 regarding serious neuropsychiatric events including depression, anxiety, sleep disturbances, and suicidal thoughts—risks that should be carefully weighed against benefits, particularly in mild disease. 2

Dose-Response Relationship

No dose-related increase in headache was observed even at doses up to 200 mg per day (20 times the recommended dose) administered for 5 months, further supporting that headache is not a medication-induced adverse effect. 3

References

Guideline

Long-Term Risks of Montelukast

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

Clinical safety and tolerability of montelukast, a leukotriene receptor antagonist, in controlled clinical trials in patients aged > or = 6 years.

Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology, 2001

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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