Common Side Effects of Singulair (Montelukast)
Montelukast is generally well-tolerated with a side effect profile similar to placebo, with the most common adverse effects being headache, upper respiratory infection, abdominal pain, and importantly, neuropsychiatric symptoms including mood changes, depression, and suicidal thoughts that warrant FDA black-box warning. 1
Most Common Side Effects in Adults and Adolescents (≥15 years)
The following adverse effects occurred in ≥1% of patients and more frequently than placebo in clinical trials 1:
- Headache (18.4% vs 18.1% placebo) - the most frequently reported side effect 1
- Upper respiratory infection (1.9% vs 1.5% placebo) 1
- Asthenia/fatigue (1.8% vs 1.2% placebo) 1
- Abdominal pain (2.9% vs 2.5% placebo) 1
- Cough (2.7% vs 2.4% placebo) 1
- Influenza (4.2% vs 3.9% placebo) 1
- Dyspepsia (2.1% vs 1.1% placebo) 1
- Dizziness (1.9% vs 1.4% placebo) 1
- Nasal congestion (1.6% vs 1.3% placebo) 1
- Rash (1.6% vs 1.2% placebo) 1
Common Side Effects in Pediatric Patients (6-14 years)
The following occurred with ≥2% frequency and more than placebo 1:
- Pharyngitis, influenza, fever, sinusitis 1
- Nausea, diarrhea, dyspepsia 1
- Otitis, viral infection, laryngitis 1
Common Side Effects in Young Children (2-5 years)
The following occurred with ≥2% frequency and more than placebo 1:
- Fever, cough, abdominal pain, diarrhea 1
- Headache, rhinorrhea, sinusitis, otitis 1
- Influenza, rash, ear pain, gastroenteritis 1
- Eczema, urticaria, varicella, pneumonia 1
Serious Neuropsychiatric Side Effects (FDA Black-Box Warning)
The FDA has issued a black-box warning regarding neuropsychiatric events that can occur with montelukast 1:
- Agitation including aggressive behavior or hostility 1
- Depression and suicidal thoughts/actions (including completed suicide) 1
- Anxiety, bad/vivid dreams, hallucinations 1
- Irritability, restlessness, sleep walking 1
- Tremor, trouble sleeping 1
Patients must be counseled about these risks and monitored for unusual behavioral or mood changes when starting montelukast 1.
Less Common but Important Side Effects
The following have been reported in post-marketing surveillance 1:
- Allergic reactions including facial/lip/tongue/throat swelling that may cause breathing difficulty, hives, and itching 1
- Increased bleeding tendency 1
- Drowsiness, pins and needles/numbness, seizures 1
- Palpitations, nose bleeds 1
- Hepatitis 1
- Joint pain, muscle aches and cramps 1
- Inflammation of the pancreas 1
Laboratory Abnormalities
Mild elevations in liver enzymes occurred in approximately 2% of patients 1:
Safety Profile Across Studies
Large real-world studies confirm the favorable safety profile 2, 3:
- In a study of 694 patients, adverse effects occurred in only 18% and included abdominal discomfort, fever, fatigue, headache, rash, and upper respiratory symptoms 2
- In a phase IV study of 5,855 adults, adverse drug reactions occurred in only 14 patients (0.23%), with no serious adverse events 3
- The side effect profile remains consistent with prolonged treatment and does not significantly change over time 1
Critical Clinical Caveat
Montelukast's side effects are generally mild and comparable to placebo in frequency, making it one of the better-tolerated asthma and allergic rhinitis medications 1, 4, 5. However, the neuropsychiatric effects, though uncommon, are serious enough to warrant the FDA black-box warning and require patient education and monitoring 1.