Drug Interaction Report

Rifampin and Mexiletine: Interaction Details

A pharmacist-reviewed analysis of the Rifampin and Mexiletine 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

Rifampin

Rifadin
+

Mexiletine

Mexitil®
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 176 documented Rifampin interactions, 130 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
delayed
Evidence
theoretical
Severity
Major

What happens

Reduced mexiletine exposure

Interaction Deep Dive

Exert caution with coadministration of rifAMPin with drugs metabolized by cytochrome P450, such as mexiletine2. Coadministration of rifAMPin and mexiletine may reduce mexiletin exposure 342. Concurrent use of rifAMPin in patients taking mexiletine resulted in a decrease in the mexiletine half-life (9 to 5 hours) and an increase in the clearance (by 50%) 51.

Why it happens (mechanism)

Increased hepatic metabolism; induction of CYP1A2-mediated metabolism of mexiletine

Literature reports

1 report — tap to read

a) Concurrent use of rifAMPin in patients taking mexiletine resulted in a decrease in the mexiletine half-life (9 to 5 hours) and an increase in the clearance (by 50%) 51.

Common questions

Can I take Rifampin and Mexiletine together?

Reduced mexiletine exposure Always confirm with your pharmacist or prescriber before making any change.

How serious is the Rifampin and Mexiletine interaction?

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

How quickly could this interaction happen?

The documented onset is "delayed". Effects tend to build up gradually over days to weeks.

How strong is the evidence for this interaction?

The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.

Questions for your pharmacist

  • Does my dose of Rifampin or Mexiletine 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 (5)

  1. Woosley RL, Wang T, Stone W, et al: Pharmacology, electrophysiology, and pharmacokinetics of mexiletine. Am Heart J 1984; 107:1058-1065. PubMed
  2. Product Information: RIFATER(R) oral tablets, rifampin, isoniazid, pyrazinamide oral tablets. sanofi-aventis US LLC (per FDA), Bridgewater, NJ, 2023. DailyMed
  3. Product Information: RIFADIN(R) IV intravenous injection, rifampin intravenous injection. sanofi-aventis US LLC (per FDA), Bridgewater, NJ, 2023. DailyMed
  4. Product Information: RIFADIN(R) oral capsules, rifampin oral capsules. sanofi-aventis US LLC (per FDA), Bridgewater, NJ, 2023. DailyMed
  5. Pentikainen PJ, Koivula IH, & Hiltunen HA: Effect of rifampicin treatment on the kinetics of mexiletine. Eur J Clin Pharmacol 1982; 23:261-266. PubMed
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Rifampin

Keep reading about Rifampin

All Rifampin interactions (176)
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Mexiletine

Keep reading about Mexiletine

All Mexiletine interactions (82) Mexiletine drug information
Also serious with: Levomethadyl Mavorixafor Fezolinetant Vernakalant
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:

Rifampin + Activated Charcoal Apple Asarabacca Beer Grapefruit Siberian Cocklebur St. John's Wort Sweet Orange + 214 more
Mexiletine + Activated Charcoal 1,3-dmaa Acacia Rigidula Active Hexose Correlated Compound (ahcc) Adrafinil African Wild Potato Ashitaba Ayahuasca + 144 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.