Digoxin and Propantheline: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Propantheline
Digoxin
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
Increased exposure
Interaction Deep Dive
Coadministration of digoxin and propantheline may increase digoxin exposure. Measure digoxin exposure before initiating concomitant drugs. Reduce digoxin concentrations by decreasing the dose by approximately 15-30% or by modifying the dosing frequency and continue monitoring. Also, monitor potential signs and symptoms of clinical toxicity is necessary when initiating, adjusting, or discontinuing propantheline12. Propantheline inhibits gastrointestinal motility. When used concurrently with a slow-dissolving digoxin preparation, increased absorption and serum digoxin levels may result. This interaction can be avoided by using digoxin formulations that dissolve rapidly according to USP standards 58.
Why it happens (mechanism)
Increased absorption due to decreased gastrointestinal motility
Literature reports
3 reports — tap to read
a) During pharmacokinetic studies, coadministration of propantheline and oral digoxin resulted in a 24% increase in digoxin serum concentrations and a 24% increase in digoxin AUC 43.
b) Serum digoxin levels with or without propantheline were studied in 13 elderly women on maintenance digoxin therapy. Propantheline 15 mg three times daily orally was administered for 10 days, resulting in an increase in serum digoxin concentrations from initial levels of 1.02 nanogram/mL (ng/mL; 1.306 nanomol/L) to 1.33 ng/mL (1.703 nanomol/L). A second group of volunteers, comprised of healthy medical students, was administered either digoxin 0.5 mg in tablet form or digoxin 0.5 mg in liquid form 30 minutes after administration of propantheline 30 mg. Administration of propantheline increased serum digoxin concentrations in the four subjects who received digoxin tablets but not in the 4 subjects who received digoxin liquid 6.
c) In a randomized, crossover study, the effect of propantheline on the absorption of various particle-size digoxin preparations was evaluated. Ten healthy volunteers each received single doses of standardized digoxin (Lanoxin® brand) 0.5 mg, micronized digoxin 0.5 mg, or large particle-size digoxin 0.5 mg. Each subject also received either propantheline 30 mg, metoclopramide 10 mg, or placebo with each digoxin dose, for a total of 9 treatment combinations, separated by at least 2 weeks. Neither standardized nor micronized digoxin preparations were affected by the coadministration of propantheline. However, absorption of the large particle-size preparation was increased by concomitant administration of propantheline compared with placebo 7.
Common questions
Can I take Digoxin and Propantheline together?
Increased exposure Always confirm with your pharmacist or prescriber before making any change.
How serious is the Digoxin and Propantheline interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "rapid". Effects can appear quickly, often within about 24 hours of combining the drugs.
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 Digoxin or Propantheline 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 (8)
- Product Information: LANOXIN(R) oral tablets, digoxin oral tablets. Concordia Pharmaceuticals Inc (per FDA), Kansas City, MO, 2019. DailyMed
- Product Information: DIGOXIN oral tablets, digoxin oral tablets. Aurobindo Pharma USA, Inc. (per Dailymed), East Windsor, NJ, May. DailyMed
- Product Information: DIGOXIN intravenous injection, digoxin intravenous injection. Hikma Pharmaceuticals USA Inc. (per Dailymed), Berkeley Heights, NJ, 2023. DailyMed
- Product Information: LANOXIN® intravenous, intramuscular injection, digoxin intravenous, intramuscular injection. Covis Pharma (per FDA), King of Prussia, PA, 2025. DailyMed
- Product Information: Pro-Banthine(R), propantheline. G.D. Searle & Co. Chicago, IL, 1994. DailyMed
- Manninen V, Melin J, Apajalahti A, et al: Altered absorption of digoxin in patients given propantheline and metoclopramide. Lancet 1973a; 1:398-399. PubMed
- Johnson BF, O'Grady J, & Bye C: The influence of digoxin particle size on absorption of digoxin and the effect of propantheline and metoclopramide. Br J Clin Pharmacol 1978; 5:465-467. DOI
- Manninen V, Apajalahti A, Simonen H, et al: Effect of propantheline and metoclopramide on absorption of digoxin. Lancet 1973b; 1:1119-1119. PubMed
Keep reading about Propantheline
Keep reading about Digoxin
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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