Cyclopenthiazide and Digoxin: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Cyclopenthiazide
No brand names on recordDigoxin
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 risk of digitalis toxicity (nausea, vomiting, arrhythmias)
Interaction Deep Dive
The most common cause of digitalis toxicity is concurrent use of a digitalis glycoside and a potassium-wasting diuretic. If a digitalis glycoside and a thiazide diuretic are used concurrently, monitor the patient for ECG signs of potassium depletion, and consider potassium supplementation1.
Why it happens (mechanism)
Diuretic-induced hypokalemia and hypomagnesemia enhance Na-K-ATPase inhibition by cardiac glycosides
Literature reports
1 report — tap to read
a) The incidence of digitalis intoxication in hospitalized patients varies between 8% to 35%, with mortality attributable to toxicity ranging from 3% to 21% 23. Twenty-four percent of 144 patients on combination therapy of digoxin plus diuretic experienced digoxin toxicity, compared to only 9% of 53 patients on digoxin alone 4. Other authors reported that of 88 patients intoxicated with digitalis, 69% were also on diuretics (30 on chlorothiazide) 5. One author found that 19 of 25 (75%) patients with digitalis toxicity were also on diuretics 6. Another study concludes that diuretic therapy was thought to be a primary or contributory factor in precipitating digitalis intoxication in 40% of patients showing adverse reactions 7. The thiazides have the potential of producing hypokalemia in a large number of patients. It has been demonstrated that 40% of patients treated for more than one week with chlorothiazide and without a potassium supplement will develop hypokalemia (serum potassium of 3.5 mEq/L or less) 8. Because intracellular potassium may be reduced, even though the serum potassium is normal or even elevated, electrocardiographic signs of potassium depletion may be of greater value than serum potassium levels 8.
Common questions
Can I take Cyclopenthiazide and Digoxin together?
Increased risk of digitalis toxicity (nausea, vomiting, arrhythmias) Always confirm with your pharmacist or prescriber before making any change.
How serious is the Cyclopenthiazide and Digoxin 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 "established". Well documented — supported by controlled studies or strong clinical data.
Questions for your pharmacist
- Does my dose of Cyclopenthiazide or Digoxin 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)
- Gilman AG, Rall TW, Nies AS, et alGilman AG, Rall TW, Nies AS, et al (Eds): Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th. Macmillan Publishing Co, New York, NY, 1990.
- Smith TW & Haber E: Digitalis (Fourth of four parts). N Engl J Med 1973; 289:1125-1129.
- Gerbino PP: Digitalis glycoside intoxication - A preventative role for the pharmacist. Am J Hosp Pharm 1973; 30:499-504.
- Hurwitz N & Wade OL: Intensive hospital monitoring of adverse reactions to drugs. Br Med J 1969; 1:531-536. PubMed
- Rodensky PL & Wasserman F: Observation on digitalis intoxication. Arch Intern Med 1961; 108:171.
- Soffer A: The changing clinical picture of digitalis intoxication. Arch Intern Med 1961; 107:681. DOI
- Tawakkol AA, Nutter DO, & Massumi RA: A prospective study of digitalis toxicity in a large city hospital. Med Ann DC 1967; 36:402-409.
- Jorgensen AW & Sorensen OH: Digitalis intoxication: A comparative study on the incidence of digitalis intoxication during the periods 1950-52 and 1964-66. Acta Med Scand 1970; 188:179-183.
Keep reading about Cyclopenthiazide
Keep reading about Digoxin
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