Safety and Scheduling of Montelukast (Singulair) and Hydroxyzine Together
It is safe to take montelukast (Singulair) and hydroxyzine together, and no dose adjustments or special scheduling precautions are required for this combination. The FDA drug label for montelukast explicitly states that it has been used concomitantly with sedative hypnotics and antihistamines in clinical studies without evidence of clinical adverse interactions 1.
Evidence for Safety
No Drug-Drug Interactions
The official FDA labeling for Singulair confirms that montelukast was used concomitantly with a wide range of commonly prescribed drugs in clinical studies without evidence of clinical adverse interactions, specifically including sedative hypnotics 1. Hydroxyzine, as a sedating antihistamine, falls into this category.
From a pharmacokinetic perspective, montelukast does not inhibit major cytochrome P450 enzymes (CYP 3A4, 2C9, 1A2, 2A6, 2C19, or 2D6) at therapeutic concentrations 1. This means montelukast will not interfere with the metabolism of hydroxyzine or increase its sedative effects through drug interactions.
Clinical Use in Guidelines
British dermatology guidelines for urticaria management explicitly describe combining antihistamines (including hydroxyzine) with leukotriene receptor antagonists like montelukast 2. The guidelines note that antileukotrienes may be taken in addition to an H1 antihistamine for poorly controlled urticaria 2. This demonstrates established clinical practice of using these medications together.
Scheduling Recommendations
Montelukast Timing
- For asthma or allergic rhinitis: Take once daily in the evening 1
- For exercise-induced bronchoconstriction: Take at least 2 hours before exercise 1
- Can be taken with or without food 1
Hydroxyzine Timing
- For urticaria: Commonly dosed at night (10-50 mg) when combined with non-sedating antihistamines during the day 2
- The sedating effect can help patients sleep better 2
Combined Scheduling Strategy
Take montelukast in the evening (as recommended for asthma/allergic rhinitis) and hydroxyzine at bedtime. This approach:
- Aligns with montelukast's standard evening dosing
- Leverages hydroxyzine's sedating properties for nighttime symptom control
- Minimizes daytime sedation from hydroxyzine
If both medications are being used for allergic conditions, they can be taken at the same time in the evening without concern for interactions.
Important Clinical Considerations
Montelukast Neuropsychiatric Warning
The FDA issued a black box warning in 2020 regarding serious behavioral and mood-related changes with montelukast, including suicidal thoughts or actions 3, 1. The FDA recommends that benefits may not outweigh risks when symptoms are mild and can be adequately treated with alternative therapies 3.
Monitor patients for: agitation, aggressive behavior, anxiousness, depression, hallucinations, insomnia, irritability, suicidal thoughts, and other neuropsychiatric symptoms 1. Advise patients and caregivers to be alert for behavioral changes 1.
Recent large observational studies show conflicting results: one Swedish study of 74,291 children found no increased risk of neuropsychiatric events 4, while a Danish study found increased risk particularly in younger adults aged 18-29 years 5.
Hydroxyzine Precautions
- Avoid in pregnancy, especially first trimester - hydroxyzine is specifically contraindicated in early pregnancy 2
- Avoid in severe liver disease due to sedating effects 2
- Reduce dose by half in renal impairment (creatinine clearance 10-20 mL/min) 2
- Causes sedation and anticholinergic effects 2
When This Combination Makes Sense
This combination is most appropriate for:
- Patients with allergic rhinitis and asthma requiring both medications for separate indications
- Patients with urticaria inadequately controlled by antihistamines alone who also have asthma
- Patients who tolerate both medications individually
Do not take an additional dose of montelukast within 24 hours of a previous dose 1. If a dose is missed, take the next dose at the regular time without doubling up 1.