Sulfamethoxazole and Disopyramide: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Disopyramide
Sulfamethoxazole
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
An increased risk of cardiotoxicity (QT prolongation, torsades de pointes, cardiac arrest)
Interaction Deep Dive
Even though no formal drug interaction studies have been done, the coadministration of Class IA antiarrhythmics and other drugs known to prolong the QTc interval is not recommended3. Cotrimoxazole has demonstrated QT prolongation at therapeutic doses 4.
Why it happens (mechanism)
Additive effects on QT prolongation
Literature reports
2 reports — tap to read
a) Eight healthy men received oral sustained-release procainamide 500 mg every six hours for three days, alone and with oral trimethoprim 200 mg daily for four days. Trimethoprim coadministration increased the area under the concentration-time curve (AUC) of procainamide from 19.9 mg/h/L to 32.5 mg/h/L, representing a 63% increase. Mean steady-state procainamide concentrations also increased from 1.6 mcg/mL to 2.7 mcg/mL. Likewise, trimethoprim increased the AUC of N-acetylprocainamide (NAPA), the active metabolite of procainamide, by 52% (14.1 mg/hr/L vs. 21.4 mg/hr/L). NAPA plasma concentrations increased from 1.2 mcg/mL to 1.8 mcg/mL. Renal clearance of procainamide and NAPA decreased by 47% and 13%, respectively. A small but significant increase in the QTc interval was noted with procainamide administration, and this interval further increased with trimethoprim cotherapy 1.
b) Ten healthy volunteers participated in an open, randomized, placebo-controlled, two-period crossover study by 2 to determine the effects of trimethoprim and procainamide coadministration. Subjects received trimethoprim 100 mg or placebo twice daily on days 1 through 3 of each study period. On day 4, procainamide 1000 mg was administered orally as a single dose with trimethoprim 200 mg or placebo, and another dose of trimethoprim 100 mg or placebo was given 12 hours later. Each treatment period was separated by at least a one-week washout period. Trimethoprim decreased the renal clearance of procainamide by 45% (487 mL/min vs. 267 mL/min) and also decreased the clearance of the active metabolite of procainamide, N-acetylprocainamide (NAPA), by 26% (275 mL/min vs. 192 mL/min) as compared to placebo. The area under the concentration-time curve (AUC) increased by 39% for procainamide (19.8 mg/h/L vs. 27.6 mg/h/L) and 27% for NAPA (9.1 mg/h/L vs. 11.4 mg/h/L). Procainamide and NAPA are weak bases and undergo extensive renal tubular secretion. Trimethoprim is 50% to 60% excreted unchanged in the urine via glomerular filtration, tubular secretion, and reabsorption. In the case of trimethoprim and procainamide coadministration, both drugs may be competing for tubular secretion, causing a saturation of this route of elimination. This results in procainamide accumulation, and the potential for procainamide toxicity.
Common questions
Can I take Sulfamethoxazole and Disopyramide together?
An increased risk of cardiotoxicity (QT prolongation, torsades de pointes, cardiac arrest) Always confirm with your pharmacist or prescriber before making any change.
How serious is the Sulfamethoxazole and Disopyramide 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.
Questions for your pharmacist
- Does my dose of Sulfamethoxazole or Disopyramide 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 (4)
- Kosoglou T, Rocci ML Jr. & Vlasses PH: Trimethoprim alters the disposition of procainamide and N-acetylprocainamide. Clin Pharmacol Ther 1988; 44:467-477. DOI
- Vlasses PH, Kosoglou T, Chase SL, et al: Trimethoprim inhibition of the renal clearance of procainamide and N-acetylprocainamide. Arch Intern Med 1989; 149:1350-1353. DOI
- Product Information: Quinaglute Dura-tabs(R), quinidine gluconate. Berlex Laboratories, Wayne, NJ, 1999. DailyMed
- Lopez JA, Harold JG, Rosenthal MC, et al: QT prolongation and torsades de pointes after administration of trimethoprim-sulfamethoxazole. Am J Cardiol 1987; 59:376-377. PubMed
Keep reading about Disopyramide
Keep reading about Sulfamethoxazole
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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