Drug Interaction Report

Montelukast and Phenobarbital: Interaction Details

A pharmacist-reviewed analysis of the Montelukast and Phenobarbital interaction: the documented clinical effects, severity rating, onset, mechanism, and management considerations, with cited references throughout.

AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature

Montelukast

Singulair Singulair®
+

Phenobarbital

Fidoquel Sezaby
Dr. Brian Staiger, PharmD, BCPS
Medically reviewed by
Dr. Brian Staiger, PharmD, BCPS
Updated Aug 8, 2026
Editorial policy · Data sources
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Interaction severity
Major
Potentially serious — often needs a change or close monitoring.
How we grade severity & evidence

Severity levels

  • Contraindicated: These should generally not be used together.
  • Major: Potentially serious — often needs a change or close monitoring.
  • Moderate: Can be significant — usually manageable with monitoring.
  • Minor: Usually limited clinical impact.

Evidence grades

  • Established: Well documented — supported by controlled studies or strong clinical data.
  • Probable: Good supporting evidence, though not definitively proven.
  • Suspected: Some evidence suggests this interaction, but it is not well established.
  • Possible: Limited or conflicting evidence; the interaction may occur.
  • Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.

Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.

Of 18 documented Montelukast interactions, 14 are rated major — including this one.
Worried about symptoms right now? Contact your pharmacist or prescriber, or call Poison Control at 1-800-222-1222 (US). Call 911 for an emergency.
Onset
unspecified
Evidence
probable
Severity
Major

What happens

Reduced montelukast exposure and reduced efficacy of montelukast

Interaction Deep Dive

Concomitant use of PHENobarbital (a CYP2C8 inducer) with montelukast (a CYP2C8 substrate) may decrease montelukast exposure, which may reduce the efficacy of montelukast. If concomitant use cannot be avoided, closely monitor neonates and consider increasing the dosage of the montelukast accordingly1. In an interaction study, coadministration of PHENobarbital with single dose of montelukast 10 mg decreased the AUC of montelukast by 40% approximately 2.

Why it happens (mechanism)

Induction of CYP2C8-mediated metabolism of montelukast by PHENobarbital

Literature reports

1 report — tap to read

a) In an interaction study, coadministration of PHENobarbital with single dose of montelukast 10 mg decreased the AUC of montelukast by 40% approximately 2.

Common questions

Can I take Montelukast and Phenobarbital together?

Reduced montelukast exposure and reduced efficacy of montelukast Always confirm with your pharmacist or prescriber before making any change.

How serious is the Montelukast and Phenobarbital interaction?

It is rated major. Potentially serious — often needs a change or close monitoring.

How quickly could this interaction happen?

The documented onset is "unspecified". The timing of this interaction is not well characterized.

How strong is the evidence for this interaction?

The evidence is graded "probable". Good supporting evidence, though not definitively proven.

From our Q&A

Real reader questions about these medications, each personally answered by our pharmacist:

Questions for your pharmacist

  • Does my dose of Montelukast or Phenobarbital need adjusting while I take them together?
  • What symptoms should prompt me to call you or my prescriber right away?
  • Does the timing of my doses matter for this combination?
  • Is there a safer alternative to one of these medications for me?

References (2)

  1. Product Information: SEZABY(TM) intravenous injection, phenobarbital sodium intravenous injection. Sun Pharmaceutical Industries Inc (per manufacturer), Cranbury, NJ, 2022. DailyMed
  2. Product Information: Singulair(R), montelukast sodium. Merck & Co. Inc. Whitehouse Station, NJ, 2003. DailyMed
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Montelukast

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All Phenobarbital interactions (219)
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Beyond drug–drug

These medications also interact with supplements

Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:

Phenobarbital + 1,4-butanediol Activated Charcoal Beer Gamma-hydroxybutyrate (ghb) Henbane Kava L-tryptophan Scopolia + 166 more

major · moderate · minor — check everything you take with our drug–supplement interaction checker.

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This information is for education, not a substitute for professional medical advice. Do not start, stop, or change any medication without talking to your pharmacist or prescriber.