Theophylline and Mexiletine: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Mexiletine
Theophylline
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.
What happens
Theophylline toxicity (nausea, vomiting, palpitations, seizures)
Interaction Deep Dive
The concurrent use of mexiletine and theophylline has been demonstrated to increase theophylline levels (ie, 30% to 200%)2615.
Why it happens (mechanism)
Decreased hepatic metabolism
Literature reports
3 reports — tap to read
a) Several controlled studies in healthy volunteers have shown that coadministration of mexiletine and theophylline results in decreased plasma clearance of theophylline 1234. The decrease in plasma clearance appears to be due to mexiletine inhibition of demethylation of theophylline 2. Several cases of theophylline toxicity have been reported in patients receiving both drugs 561.
b) A 74-year-old patient taking sustained-release oral theophylline 300 mg twice a day had a steady state trough serum level of 15.3 mcg/mL. A few days after the initiation of oral mexiletine 200 mg three times a day, the patient experienced symptoms of theophylline toxicity (anorexia, nausea, vomiting). After 2 weeks of combined therapy, the theophylline serum concentration was 25 mcg/mL. The dose of theophylline was reduced to 100 mg twice a day and the symptoms resolved; a subsequent level was 14.2 mcg/mL 5.
c) Three cases were reported in which mexiletine was added to theophylline therapy 6. Theophylline serum concentrations increased by approximately 2 to 2.6 times what they were before mexiletine was added to therapy. No effect on mexiletine pharmacokinetics was observed.
Common questions
Can I take Theophylline and Mexiletine together?
Theophylline toxicity (nausea, vomiting, palpitations, seizures) Always confirm with your pharmacist or prescriber before making any change.
How serious is the Theophylline 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 "probable". Good supporting evidence, though not definitively proven.
Questions for your pharmacist
- Does my dose of Theophylline 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 (6)
- Loi CM, Wei XX, & Vestal RE: Inhibition of theophylline metabolism by mexiletine in young male and female nonsmokers. Clin Pharmacol Ther 1991; 49:571-580. PubMed
- Ueno K, Miyai K, Kato M, et al: Mechanism of interaction between theophylline and mexiletine. DICP 1991; 25:727-730. DOI
- Hurwitz A, Vacek JL, Botteron GW, et al: Mexiletine effects on theophylline disposition. Clin Pharmacol Ther 1991; 50:299-307. PubMed
- Stoysich AM, Mohiuddin SM, Destache CJ, et al: Influence of mexiletine on the pharmacokinetics of theophylline in healthy volunteers. J Clin Pharmacol 1991; 31:354-357. DOI
- Katz A, Buskila D, & Sukenik S: Oral mexiletine - theophylline interaction. Int J Cardiol 1987; 17:227. PubMed
- Ueno K, Miyai K, Seki T, et al: Interaction between theophylline and mexiletine. DICP 1990; 24:471-472. DOI
Keep reading about Mexiletine
Keep reading about Theophylline
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:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
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