Digoxin (renally eliminated cardiac glycoside)
AMT in HFrEF · Class IIaRemoval by dialysis
What each drug's prescribing information says about removal by (haemo)dialysis. Where the label is silent, this page says so rather than inferring from protein binding.
- DigoxinNot removed (or not meaningfully removed)
“Digoxin is not effectively removed from the body by dialysis, exchange transfusion, or during cardiopulmonary bypass because most of the drug is bound to extravascular tissues.”
Drugs and doses
| Drug | Brands | Start | Target | Kidney dosing |
|---|---|---|---|---|
| Digoxin | Lanoxin | 62.5 µg o.d. (ESC Table 11); label: maintenance dose from lean body weight and creatinine clearance (Table 3) | 250 µg o.d. (ESC Table 11), titrated to serum level (ESC: <1.2 ng/mL; AHA: 0.5–<0.9 ng/mL) | Renally cleared (50–70% unchanged in urine). Reduce maintenance dose in proportion to creatinine clearance (FDA Table 3 gives once-daily doses for CrCl 10–100 mL/min by lean body weight); longer time to steady state; check levels; not removed by dialysis. |
Status by kidney stage
| Stage | Initiate | Continue |
|---|---|---|
| G1 | Recommended ESC 2026 Class IIa (LVEF ≤40% despite optimal FMT); digoxin dosed by lean weight/CrCl and serum level. | Recommended Continue with serum-level monitoring. |
| G2 | Recommended As G1; digoxin maintenance dose already scales with CrCl (label Table 3). | Recommended Continue with level monitoring. |
| G3a | Use with caution Class IIa applies, but digoxin needs CrCl-based dose reduction and closer level checks (DGK: special caution at GFR <60); digitoxin needs no renal adjustment. | Use with caution Continue; recheck digoxin level after any eGFR decline or dose change. |
| G3b | Use with caution As G3a; digoxin dose reduced per CrCl; DIG showed no effect modification by eGFR. | Use with caution Continue with level and renal-function monitoring. |
| G4 | Use with caution ESC CVD–CKD Class IIa for eGFR >20 (text says ≥20); digoxin requires substantial dose reduction and level monitoring at eGFR <30; digitoxin preferable. | Use with caution Continue with close level/K+ monitoring; consider switching to digitoxin where available. |
| G5 | Use with caution No guideline support; digoxin label still provides reduced doses down to CrCl 10 mL/min with prolonged half-life; digitoxin SmPC: check requirement/reduce dose at GFR <10. | Use with caution High toxicity risk with digoxin; monitor levels and potassium closely; digitoxin preferred. |
| dialysis | Use with caution Neither glycoside is removed by dialysis; digoxin half-life 3.5–5 days in anuria; observational HD data link digoxin to higher mortality, especially with low pre-dialysis K+. No guideline recommendation; specialist use only, digitoxin preferred. | Use with caution Continue only with level monitoring and attention to pre-dialysis potassium (dialysis-induced hypokalaemia sensitises to glycoside toxicity). |
| aki | Use with caution Do not start/up-titrate digoxin during an acute GFR fall: excretion falls and steady state is delayed; reassess level once kidney function stabilises. Digitoxin is less affected. | Use with caution Check serum digoxin and potassium; hold or reduce dose if level high (DGK: pause 2 days, up to 5 days in advanced renal failure). |
| transplant | Use with caution No transplant-specific guidance, but cyclosporine raises digoxin concentrations; measure levels before and after starting calcineurin-inhibitor co-therapy. | Use with caution As initiate. |
Cutoffs recorded from the sources
- other < 1.2 ng/mL → target ceiling (continue; digoxin)“A serum digoxin concentration <1.2 ng/mL should be used as a target during ongoing therapy.” — esc2026, p. 34
- other between 0.5,0.9 ng/mL → target range (continue; digoxin)“Individualized variable dose to achieve serum digoxin concentration 0.5–<0.9 ng/mL” — aha2022, p. 52, Table 13
- other > 2 ng/mL → toxicity without added benefit (dose_reduce; digoxin)“Serum digoxin levels less than 0.5 ng/mL have been associated with diminished efficacy, while levels above 2 ng/mL have been associated with increased toxicity without increased benefit.” — fda-digoxin, Section 2.5 Monitoring
- other > 1.2 ng/mL → increasing adverse reactions (dose_reduce; digoxin)“As digoxin serum levels increase above 1.2 ng/mL, there is a potential for increase in adverse reactions. Furthermore, lower potassium levels increases the risk for adverse reactions.” — fda-digoxin, Section 10.1 Overdosage
- potassium between 4,5.5 mmol/L → maintain (correct hypokalaemia) when toxicity suspected (continue; digoxin)“Correct hypokalemia by administering potassium so that serum potassium is maintained between 4.0 and 5.5 mmol/L.” — fda-digoxin, Section 10.2 Treatment
- egfr <= 20 mL/min/1.73m2 → caution (initiate; digoxin, digitoxin)“Additional medical therapy with cardiac glycosides (digoxin or digitoxin) should be considered in patients with HFrEF and CKD with eGFR >20 mL/min/1.73 m2 to reduce the risk of HF hospitalization and death.” — esc2026-ckd, p. 40, Recommendation Table 15
- egfr < 30 mL/min/1.73m2 → intensified level monitoring; substantial digoxin dose reduction (continue; digoxin)“Digoxin is about 75% renally excreted and requires substantial dose reduction and monitoring of digoxin levels, particularly at eGFR <30 mL/min/1.73 m2.” — esc2026-ckd, p. 62
- egfr < 60 mL/min → caution: accumulation risk (digoxin) (dose_reduce; digoxin)“Besondere Vorsicht ist geboten bei Patienten, die eine GFR < 60 ml/min aufweisen, da hier das Akkumulationsrisiko hoch ist, insbesondere wenn die Nierenfunktion durch Infektionen, Exsikkose oder andere akute Erkrankungen weiter abnimmt.” — dgk2022-digitoxin, p. 3
- creatinine_abs > 3 mg/dL → outside DIG trial evidence (caution) (initiate; digoxin)“In the DIG study (Digitalis Investigation Group) with digoxin, patients were included up to a serum creatinine level of 3.0 mg/dL, which roughly corresponds to an eGFR of around 20 mL/min/1.73 m2.” — beldhuis2022, p. 12
- other > 40 % → not indicated (HF indication) (initiate; digoxin, digitoxin)“A cardiac glycoside (digoxin or digitoxin) should be considered in patients with symptomatic HFrEF with LVEF ≤40%, despite optimal FMT, to reduce the risk of HFH” — esc2026, p. 37
- potassium < 4.3 mEq/L (pre-dialysis) → higher mortality with rising digoxin level in HD (observational) (continue; digoxin)“This increased mortality risk with level was most pronounced in patients with lower predialysis serum potassium (K) levels (HR 2.53 [P = 0.01] for K <4.3 mEq/L versus HR 0.86 [P = 0.35] for K >4.6 mEq/L).” — chan2010, Abstract
Trial evidence (informational)
- DIG · HF with LVEF ≤45%, sinus rhythm (n=6800), pre-beta-blocker eraall-cause mortality: RR 0.99 (CI 0.91–1.07): neutral“On the other hand, randomization to digoxin had no apparent effect on mortality (RR 99%, with confidence limits of 91-107%).” — fda-digoxin, Section 14.1 DIG Trial
- DIG · as aboveHF hospitalisation: RR 0.72 for ≥1 HF hospitalisation; RR 0.75 for number of HF hospitalisations“Randomization to digoxin was again associated with a significant reduction in the incidence of hospitalization, whether scored as number of hospitalizations for heart failure (relative risk 75%), risk of having at least one such hospitalization during the trial (RR 72%), or number of hospitalizations for any cause (RR 94%).” — fda-digoxin, Section 14.1 DIG Trial
Acute kidney injury
No guideline AKI rule. Digoxin excretion falls with any GFR decline (including drug-induced), so AKI raises toxicity risk: check level and K+, hold or reduce. Digitoxin is largely non-renally cleared but renal dysfunction remains a common trigger of digitalis toxicity.
“A decline in GFR or tubular secretion, as from ACE inhibitors, angiotensin receptor blockers, nonsteroidal anti-inflammatory drugs [NSAIDS], COX-2 inhibitors may impair the excretion of digoxin.”
“Because of the prolonged elimination half-life, a longer period of time is required to achieve an initial or new steady-state serum concentration in patients with renal impairment than in patients with normal renal function.”
“Da Digoxin deutlich mehr über die Niere eliminiert wird als Digitoxin, muss eher mit einer Überdosierung gerechnet werden, insbesondere bei Verschlechterung der Nierenfunktion.”
Bauersachs J, Maier L, ter Horst N, Bavendiek U. Lieferengpass Digitoxin: Stellungnahme der Deutschen Gesellschaft für Kardiologie. Kardiologie 2022 (2022)· p. 1, Zusammenfassung Source
Dialysis
Neither glycoside is removed by dialysis. Digoxin: anuric half-life 3.5–5 days; large HD cohort (Chan et al., via Inampudi 2018) showed 28% higher mortality, worst with low pre-dialysis K+; a small cohort suggested intermittent low dose is tolerated. Digitoxin: minimally dialysed; hypokalaemia from dialysis sensitises. No guideline recommendation.
Trials: Chan 2010 JASN (observational, 120,864 incident HD patients), Li 2014 retrospective HD cohort (n=67)
“Digoxin is not effectively removed from the body by dialysis because of its large extravascular volume of distribution.”
“In conclusion, digoxin use among patients who are on hemodialysis associates with increased mortality, especially among those with low predialysis K concentrations.”
Chan KE et al. Digoxin associates with mortality in ESRD. J Am Soc Nephrol 2010 (PMID 20576808, abstract) (2010)· Abstract Source“however, Chan et al (7) reported that digoxin use at a similar dose among patients who were on hemodialysis was associated with an increased mortality, particularly among those with low predialysis K+ concentrations.”
Li X, et al. Intermittent low-dose digoxin may be effective and safe in patients with chronic heart failure undergoing maintenance hemodialysis. Exp Ther Med 2014 (PMC4218698) (2014)· Introduction Source“Forcierte Diurese, Peritoneal- und Hämodialyse haben sich als unwirksam zur Digitoxin-Elimination erwiesen.”
Kidney transplant
No transplant-specific guidance; cyclosporine increases digoxin concentrations (label), so levels need monitoring.
“Alprazolam, azithromycin, cyclosporine, diclofenac, diphenoxylate, epoprostenol, esomeprazole, ibuprofen, ketoconazole, lansoprazole, metformin, omeprazole”
Albuminuria
No source differentiates glycoside use by albuminuria category.
No verbatim statement found for this cell.
Monitoring
Digoxin: level just before next dose or ≥6 h post-dose, at steady state (7–10 days; longer in CKD) after start and each change; electrolytes and renal function periodically; keep K+ high-normal. Digitoxin: level at ~6 weeks (DIGIT-HF), sample before daily dose.
“Obtain serum digoxin concentrations just before the next scheduled LANOXIN dose or at least 6 hours after the last dose.”
“Low body weight, advanced age or impaired renal function, hypokalemia, hypercalcemia, or hypomagnesemia may predispose to digoxin toxicity.”
“Digoxin levels should be drawn at a sufficient time after initiation/change to allow steady state (8–10 days).”
Beldhuis 2022 Circulation: Evidence-based medical therapy in HFrEF patients with CKD (2022)· p. 12 Source“High-normal K+ levels may be desirable in patients with HF, especially if they are taking digoxin.”
2026 ESC Guidelines for the management of heart failure: Supplementary data (Tables S1-S26) (2026)· p. 18, Table S9 (MRA) Source
In-hospital initiation
IV digoxin may be used for acute rate control in haemodynamically unstable HFrEF with AF (cardioversion first); label: not recommended in acute MI.
“In patients with HFrEF who are haemodynamically unstable, i.v. amiodarone or digoxin may be used to achieve acute control of heart rate and improve haemodynamics, although acute electrical cardioversion to restore sinus rhythm should be first choice.”
“LANOXIN is not recommended in patients with acute myocardial infarction because digoxin may increase myocardial oxygen demand and lead to ischemia.”
Outpatient
Chronic use in symptomatic HFrEF on optimal FMT to reduce HF hospitalisation; DIGIT-HF tested low-dose digitoxin in outpatients including AF.
“The trial included most patients in NYHA class III and, contrary to the DIG trial, also included patients with AF.”
Where sources disagree
Serum digoxin target
“A serum digoxin concentration <1.2 ng/mL should be used as a target during ongoing therapy.”
“Individualized variable dose to achieve serum digoxin concentration 0.5–<0.9 ng/mL”
“Serum digoxin levels less than 0.5 ng/mL have been associated with diminished efficacy, while levels above 2 ng/mL have been associated with increased toxicity without increased benefit.”
“As digoxin serum levels increase above 1.2 ng/mL, there is a potential for increase in adverse reactions. Furthermore, lower potassium levels increases the risk for adverse reactions.”
“Nach 7 bis 10 Tagen sollte der Digoxin-Spiegel gemessen werden (Zielspiegel 0,5–0,9 ng/ml bzw. 0,65–1,15 nmol/l)”
Bauersachs J, Maier L, ter Horst N, Bavendiek U. Lieferengpass Digitoxin: Stellungnahme der Deutschen Gesellschaft für Kardiologie. Kardiologie 2022 (2022)· p. 3 Source
Tool uses aha2022: Label's implied 0.5–2 ng/mL range is outdated and its own overdosage section flags >1.2. Conservative default: target 0.5–0.9 ng/mL (AHA/DGK), hard ceiling <1.2 ng/mL (ESC 2026 + label 10.1); user-adjustable.
eGFR floor for glycoside recommendation (>20 vs ≥20 vs label doses to CrCl 10)
“Additional medical therapy with cardiac glycosides (digoxin or digitoxin) should be considered in patients with HFrEF and CKD with eGFR >20 mL/min/1.73 m2 to reduce the risk of HF hospitalization and death.”
2026 ESC Guidelines for the management of cardiovascular disease and chronic kidney disease, in collaboration with the ERA (2026)· p. 40, Recommendation Table 15 Source“Cardiac glycosides (digoxin or digitoxin) should be considered in patients with eGFR ≥20 mL/min/1.73 m2 to reduce the risk of HF hospitalizations.”
2026 ESC Guidelines for the management of cardiovascular disease and chronic kidney disease, in collaboration with the ERA (2026)· p. 37 Source“10 mL/min | 62.5* | 125 | 125 | 187.5 | 187.5 | 187.5 | 250 | 19 |”
Tool uses fda-digoxin: Label permits dose-adjusted use at any CrCl ≥10, so no hard floor; use the ESC CVD–CKD rec-table value (>20) for recommendation strength (caution at ≤20). The CKD guideline's own text (≥20) differs; flag to owner.
Class of recommendation and population (ESC 2026 vs AHA 2022)
“In 2026, this is upgraded to Class IIa: A cardiac glycoside (digoxin or digitoxin) should be considered in patients with symptomatic HFrEF with LVEF ≤40%, despite optimal FMT, to reduce the risk of HFH.”
2026 ESC HF Guideline lecture slides (2026)· slide 31“In patients with symptomatic HFrEF despite GDMT (or who are unable to tolerate GDMT), digoxin might be considered to decrease hospitalizations for HF”
“*Digoxin remains indicated for HFrEF, but there are no contemporary data to warrant additional comment in this document.”
2024 ACC Expert Consensus Decision Pathway for Treatment of HFrEF (2024)· p. 6, Table 1 footnote Source
Tool uses esc2026: ESC-centric per brief (IIa, LVEF ≤40%, digitoxin included, no sinus-rhythm requirement); show ACC/AHA 2b in the ACC/AHA view.
Digoxin in maintenance haemodialysis
“Among 120,864 incident hemodialysis patients, digoxin use associated with a 28% increased risk for death (hazard ratio [HR] 1.28; 95% confidence interval 1.25 to 1.31).”
Chan KE et al. Digoxin associates with mortality in ESRD. J Am Soc Nephrol 2010 (PMID 20576808, abstract) (2010)· Abstract Source“In conclusion an intermittent lower dose of digoxin has beneficial effects and clinical safety in hemodialysis patients with congestive heart failure.”
Li X, et al. Intermittent low-dose digoxin may be effective and safe in patients with chronic heart failure undergoing maintenance hemodialysis. Exp Ther Med 2014 (PMC4218698) (2014)· Abstract Source“Digoxin is not effectively removed from the body by dialysis because of its large extravascular volume of distribution.”
Tool uses fda-digoxin: No guideline statement; label permits dose-adjusted use; observational harm signal outweighs a small retrospective benefit study, so 'caution' (not 'allowed'); owner may prefer 'not-recommended'.
Open questions
- Split the class into digoxin vs digitoxin rows for G3a–dialysis? Digitoxin needs no renal adjustment (ESC p. 35, SmPC), but it has no FDA label and supply is limited outside Germany/Austria.
- Digoxin target default: 0.5–0.9 ng/mL (AHA/DGK) with <1.2 ceiling (ESC), or ESC <1.2 only?
- Dialysis status for digoxin: 'caution' (label permits, no guideline) vs 'not-recommended' (observational mortality signal).
- ESC CVD–CKD inconsistency: rec table '>20' vs text '≥20' mL/min/1.73 m2.
- DIGIT-HF main NEJM paper (2025) is not open access; trial effect sizes are quoted from ESC 2026 and ESC CVD–CKD 2026 instead.