Digitoxin (hepatically eliminated cardiac glycoside)
AMT in HFrEF · Class IIaWhere this drug is marketed
Regulator databases and published statements, as found on 9 October 2026. Countries without a published statement are listed as unknown, not as unavailable.
- GermanyMarketed
“Digitoxin Awd | Digitoxin | Oral Use | Germany | Teva Gmbh”
European Medicines Agency. Article 57 product data (EMA/518502/2018 Rev.89), data as present in the Article 57 database on 21/09/2026: text extract of all rows with active substance digitoxin (2026)· Article 57 product data (21/09/2026), digitoxin rows Source
Authorised (EMA Article 57). Merck withdrew Digimerck from the German market from 1 January 2023 (authorisations still listed), and Digitoxin AWD (Teva) has had recurrent shortages. Market detail is outside the scope of this non-German search.
- AustriaMarketed
“Digimerck | Digitoxin | Oral Use | Austria | Merck Gesellschaft Mbh”
European Medicines Agency. Article 57 product data (EMA/518502/2018 Rev.89), data as present in the Article 57 database on 21/09/2026: text extract of all rows with active substance digitoxin (2026)· Article 57 product data (21/09/2026), digitoxin rows Source
The national SmPC is current (BASG, Stand der Information 08/2024; Z.Nr. 17.642 for 0.07 mg and 1-18969 for 0.1 mg). In 2017 BASG arranged supply of the German Digimerck injection for Austria (basg2017-digimerck). Current pharmacy availability was not verified.
- HungaryNot marketed
“Készítmény törlésének dátuma 2023.07.26”
OGYEI (Hungary) drug database record: DIGIMERCK 0,1 mg tabletta (OGYI-T-04084) (2026)· OGYEI drug database, DIGIMERCK 0,1 mg tabletta record Source
'Date of deletion of the product: 26 July 2023'. Digimerck minor 0.07 mg was deleted 21 July 2023. The Hungarian SmPC (2021) is cached as ogyei-digimerck-smpc.
- SerbiaNot marketed
“Furthermore, trial extension to Serbia was strongly delayed by COVID‐19 pandemic just after solving all regulatory issues (e.g. digitoxin is not available and approved in Serbia) mandatory for starting the trial at 10 study sites in Serbia, which significantly affected final recruitment numbers.”
Bavendiek U, et al. The DIGIT-HF trial: Key amendments of study design. Eur J Heart Fail 2025 (PMC11955316) (2025)· Section on trial conduct / COVID-19 impact Source
Serbia contributed DIGIT-HF sites using imported trial medication.
- United StatesNot marketed
“CRYSTODIGIN | DIGITOXIN | 0.2MG/ML | INJECTABLE;INJECTION | Discontinued”
Drugs@FDA: ANDA 084100 CRYSTODIGIN (digitoxin) injection, Lilly, marketing status Discontinued (2026)· Drugs@FDA, ANDA 084100 overview, Products on ANDA 084100 Source
openFDA lists only one digitoxin application (ANDA 084100, Lilly), and it is discontinued. Published statement: Sciatti 2026, Section 'The DIGIT-HF trial: design, results, and interpretation': 'A substantial proportion of the world, including the United States, does not have access to digitoxin.' Sciatti Table 1 lists commercial availability as 'Limited (Central Europe; not available in the USA)'.
- CanadaNot marketed
“Current status: Cancelled Post Market Current status date: 2001-09-05”
Health Canada Drug Product Database: DIGITALINE WELCKER TAB 0.1MG (digitoxin), DIN 00234516 (2026)· Health Canada Drug Product Database, DIN 00234516 (DIGITALINE WELCKER TAB 0.1MG) Source
DPD API: drug code 1932 is the only product with digitoxin as an active ingredient in the whole DPD ingredient file.
- NorwayNot marketed
“BACKGROUND In 2011, following a period with delivery problems, the only registered digitoxin drug in Norway was replaced with digoxin. As a result, approximately 21 000 patients had to replace digitoxin with digoxin.”
Haga C, et al. Legemiddelsikkerhet ved bytte av digitalispreparat i Norge [Drug safety associated with the change of digitalis drug in Norway]. Tidsskr Nor Laegeforen 2016;136:1714-8 (PubMed abstract, PMID 27830905) (2016)· Abstract, Background (PubMed) Source
Haga C et al. Tidsskr Nor Laegeforen 2016. The switch was followed by a transient rise in digitalis overdoses.
- FranceNot marketed
“Déclaration d'arrêt de commercialisation:19/04/1993”
ANSM (France) archive: DIGITALINE Nativelle 1 mg/ml, solution buvable en gouttes (CIS 67252439) (2026)· ANSM archive, DIGITALINE Nativelle 1 mg/ml (CIS 67252439), Présentations Source
Digitaline Nativelle (digitoxin 100 mg/100 ml oral drops). No digitoxin product appears in EMA Article 57 for France.
- United KingdomNot marketed
“For now, digitoxin isn’t routinely used or licensed for heart failure in the UK digoxin remains the go-to cardiac glycoside.”
British Cardiovascular Society Heartbeat editorial. Digitoxin in Heart Failure - A Comeback Story? (2025)· BCS editorial, 'What this means for UK health professionals' Source
The source omits punctuation between 'UK' and 'digoxin'. NHS dm+d still carries a VMP 'Digitoxin 100microgram tablets' (valid as a prescribable product, 'Actual Products Available'; cached as nhs-dmd-digitoxin), so unlicensed or imported supply may be possible. No UK marketing authorisation was found.
- Many countries (general statement)Not marketed
“However, digitoxin is not available in many countries.”
Tamargo J, Agewall S, Ambrosio G, et al. Cardiovascular pharmacotherapy in 2025. Eur Heart J Cardiovasc Pharmacother 2026 (PMC13185746) (2026)· Section 'Digitalis' Source
ESC Working Group on Cardiovascular Pharmacotherapy annual review (Eur Heart J Cardiovasc Pharmacother 2026).
No published statement found for: Netherlands; Belgium; Switzerland; Sweden / Denmark / Finland; Italy / Spain; Australia.
Removal 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.
- DigitoxinNot removed (or not meaningfully removed)
In English: Dialysis removes digitoxin only slightly, because most of it is bound to plasma proteins.
“Dialyse eliminiert Digitoxin nur geringfügig, da der größte Teil des Digitoxins an Plasmaproteine gebunden ist.”
Drugs and doses
| Drug | Brands | Start | Target | Kidney dosing |
|---|---|---|---|---|
| Digitoxin | Digitoxin AWD, Digimerck | 0.07 mg o.d. (ESC Table 11; DIGIT-HF) | 0.1 mg o.d. (ESC Table 11); DIGIT-HF serum target 8–18 ng/mL (10.5–23.6 nmol/L); 97% ended on 0.05–0.07 mg o.d. | Hepatic/enterohepatic elimination; isolated renal impairment barely affects elimination. German SmPC: requirement may fall with combined severe liver and kidney failure; check requirement/reduce dose at GFR <10 mL/min. Not removed by dialysis. |
Status by kidney stage
| Stage | Initiate | Continue |
|---|---|---|
| G1 | Recommended ESC 2026 Class IIa (LVEF ≤40% despite optimal FMT). Hepatically eliminated: no renal dose adjustment. | Recommended Continue with plasma-level monitoring. |
| G2 | Recommended As G1. | Recommended Continue with plasma-level monitoring. |
| G3a | Recommended ESC 2026 CVD–CKD Class IIa at eGFR >20 (digoxin or digitoxin) and DIGIT-HF data (no effect modification by CKD). Hepatic elimination: no renal dose adjustment in the SmPC; start at 0.05 mg o.d. when eGFR is <50 (DIGIT-HF dosing score). | Recommended Continue with plasma-level monitoring; recheck the level after any acute decline in kidney function. |
| G3b | Recommended As G3a: ESC 2026 CVD–CKD Class IIa at eGFR >20 and DIGIT-HF data; start at 0.05 mg o.d. when eGFR is <50. | Recommended As G3a. |
| G4 | Use with caution The ESC CVD–CKD recommendation covers eGFR >20 (the text says ≥20), so initiation at eGFR 15–29 straddles it: caution. No renal dose adjustment in the SmPC until GFR <10. | Allowed Continue; the SmPC advises no renal restriction above GFR 10, with level monitoring. |
| G5 | No data No data: no HF trial evidence at eGFR <15 (Beldhuis 2022); the SmPC advises checking the requirement and reducing the dose at GFR <10. | No data No data on continuation at eGFR <15; if continued, check the plasma level and the requirement at GFR <10 (SmPC). |
| dialysis | No data No data: dialysis removes digitoxin only slightly (SmPC) but there is no HF outcome evidence on dialysis (the observational mortality signal concerns digoxin). | No data No data on continuation on dialysis; individualize with nephrology input. |
| aki | Use with caution Renal dysfunction is among the most common triggers of digitalis intoxication (SmPC); do not start during an acute fall in GFR. | Use with caution Check plasma level and potassium; reduce or pause if the level is high. |
| transplant | No data No transplant-specific guidance. | No data As initiate. |
Cutoffs recorded from the sources
- other between 8,18 ng/mL (10.5–23.6 nmol/L) → target range (DIGIT-HF) (continue; digitoxin)“The target range of digitoxin serum concentration is 8–18 ng/mL (10.5–23.6 nmol/L) throughout the study.” — bavendiek2019, Methods, Study medication
- other > 35 ng/mL → toxicity (SmPC therapeutic range 10–30 ng/mL) (dose_reduce; digitoxin)“Die therapeutischen Serumkonzentrationen im Steady state liegen in der Regel zwischen 10 und 30 ng/ml; höhere Werte insbesondere über 35 ng/ml können mit toxischen Erscheinungen einhergehen.” — smpc-digitoxin-awd, Fachinformation 4.2, p. 2
- potassium < null mmol/L (below normal) → contraindicated (hypokalaemia, digitoxin SmPC) (initiate; digitoxin)“Hypokaliämie — Hyperkalziämie, Hypomagnesiämie” — smpc-digitoxin-awd, Fachinformation 4.3 Gegenanzeigen, p. 2
- 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 < 10 mL/min → check requirement, reduce digitoxin dose if needed (dose_reduce; digitoxin)“Auch wird empfohlen, den Digitoxinbedarf bei Patienten mit sehr schwerer Niereninsuffizienz (GFR < 10 ml/min) insbesondere zu Beginn der Therapie zu überprüfen und ggf. die Dosierung zu vermindern.” — smpc-digitoxin-awd, Fachinformation 4.2, p. 2
- hr < 60 bpm → excluded from DIGIT-HF (unless functional CRT) (initiate; digitoxin)“Heart rate < 60 b.p.m. (except if functional cardiac resynchronization therapy in place)” — bavendiek2019, Table 2 Exclusion criteria
- 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
Trial evidence (informational)
- DIGIT-HF · HFrEF LVEF ≤40% NYHA III/IV or LVEF ≤30% NYHA II, on contemporary FMT, AF allowedall-cause death or HF hospitalisation: 39.5% vs 44.1%; HR 0.82 (95% CI 0.69–0.98)“Over a median follow-up of 36 months, the primary composite endpoint—death from any cause or HFH—occurred in 39.5% of the digitoxin group vs 44.1% of the placebo group (HR 0.82; 95% CI 0.69–0.98; P = .03).” — esc2026, p. 34
- DIGIT-HF (CKD) · by baseline CKD statusprimary composite: no effect modification by CKD“Recently, the DIGitoxin to Improve ouTcomes in patients with advanced chronic Heart Failure (DIGIT-HF) randomized trial showed that digitoxin reduced the risk of the primary composite of all-cause death or first HF hospitalization vs placebo on top of optimal HFrEF therapy (HR 0.82, 95% CI 0.69–0.98), without effect modification by baseline CKD status.” — esc2026-ckd, p. 37
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“Bei gestörter Nierenfunktion wird die reduzierte renale Elimination von Digitoxin durch vermehrte Metabolisierung und fäkale Elimination kompensiert. Bei Patienten mit kombinierter Nieren- und Leberinsuffizienz ist dagegen mit erhöhten Digitoxinplasmaspiegeln zu rechnen.”
Fachinformation (SmPC) Digimerck 0,1 mg / 0,07 mg Tabletten, Merck Gesellschaft mbH Wien, Austria (BASG/AGES), Stand der Information 08/2024 (2024)· p. 9, Section 5.2 Elimination Source“Die Zerfallsrate beträgt 7-10% pro Tag. Die Eliminationshalbwertszeit aus dem Serum beträgt im Mittel 7 – 8 Tage.”
Fachinformation (SmPC) Digimerck 0,1 mg / 0,07 mg Tabletten, Merck Gesellschaft mbH Wien, Austria (BASG/AGES), Stand der Information 08/2024 (2024)· p. 9, Section 5.2 Elimination Source“Forcierte Diurese, Peritoneal- und Hämodialyse sind für die Digitoxinelimination unwirksam.”
Fachinformation (SmPC) Digimerck 0,1 mg / 0,07 mg Tabletten, Merck Gesellschaft mbH Wien, Austria (BASG/AGES), Stand der Information 08/2024 (2024)· p. 8, Section 4.9 Overdose Source“A veseműködés zavara esetén a digitoxin csökkent renális kiválasztását a fokozott metabolizáció és a széklettel történő elimináció kompenzálja. Csökkent veseműködés, illetve máj és vese működési zavar együttes előfordulása esetén magasabb digitoxin plasmaszintek várhatók.”
Alkalmazási előírás (SmPC) Digimerck 0,1 mg tabletta, Merck Kft., Hungary (OGYEI), document version 2021-02 (2021)· Section 5.2, Kiválasztás Source“A digitoxin dialízissel csak alig távolítható el, mert nagyrészt plazma proteinekhez kötődik.”
Alkalmazási előírás (SmPC) Digimerck 0,1 mg tabletta, Merck Kft., Hungary (OGYEI), document version 2021-02 (2021)· Section 5.2, Kiválasztás Source“Both agents share a narrow therapeutic window and require careful monitoring but differ in their metabolic elimination: digoxin is primarily eliminated through the kidneys, whereas digitoxin undergoes hepatic elimination.”
“Digoxin is renally excreted and requires close monitoring of kidney function and digoxin levels. Digitoxin undergoes enterohepatic (non-renal) elimination.”
2026 ESC Guidelines for the management of cardiovascular disease and chronic kidney disease, in collaboration with the ERA (2026)· p. 37, Section 6.2.2.1.4 Source“In contrast to digoxin, which is primarily eliminated renally by passive glomerular filtration and tubular secretion, impaired renal function does not influence elimination and half-life of digitoxin, because the reduced renal clearance is entirely compensated by extrarenal (entero-hepatic) clearance keeping the total clearance constant. Only in patients with advanced liver and renal dysfunction, total clearance of digitoxin is impaired with relevant elevation of digitoxin serum concentrations.”
Bavendiek U, et al. Simple and safe digitoxin dosing in heart failure based on data from the DIGIT-HF trial. Clin Res Cardiol 2023 (PMC10359203) (2023)· Discussion Source“In plasma, the time-course of radioactivity indicated a diminished absorption velocity of tritium compared to that of control subjects already reported and, after reaching of a pseudostate-equilibrium at 24 hr, an exponential decline with a mean half-life of 8.0 days.”
Vöhringer HF, Rietbrock N, et al. Disposition of digitoxin in renal failure. Clin Pharmacol Ther 1976;19:387-95 (PubMed abstract) (1976)· Abstract Source“Whereas steady state plasma concentrations of digoxin are altered proportionally to renal clearance of creatinine, those of digitoxin remain the same throughout a wide range of renal impairment.”
Vöhringer HF, Rietbrock N. Digitalis therapy in renal failure with special regard to digitoxin. Int J Clin Pharmacol Ther Toxicol 1981;19:175-84 (PubMed abstract) (1981)· Abstract Source“Uremia per se did not influence the in vitro binding of digitoxin. There were marked changes in digitoxin and digoxin protein binding during an 8-hr hemodialysis, digitoxin binding decreasing from 97.1% to 93.7% (p less than 0.0025) and digoxin binding from 23.5% to 15.4% (p less than 0.05).”
Storstein L. Studies on digitalis. V. Influence of impaired renal function, hemodialysis, and drug interaction on serum protein binding of digitoxin and digoxin. Clin Pharmacol Ther 1976;20:6-14 (PubMed abstract) (1976)· Abstract Source“Our data suggest that uremic patients produce more digitoxose than control patients and that digitoxin elimination is more rapid in uremic patients.”
Storstein L. Studies on digitalis. XI. Digitoxin metabolism in patients with impaired renal function. Clin Pharmacol Ther 1977;21:536-46 (PubMed abstract) (1977)· Abstract Source“Digitoxin is highly lipophilic and extensively bound to plasma proteins, has a longer half-life, is mainly eliminated in the metabolized state via urine and faeces and does not accumulate in kidney dysfunction.”
Belz GG, et al. Treatment of congestive heart failure - current status of use of digitoxin. Eur J Clin Invest 2001;31 Suppl 2:10-7 (PubMed abstract) (2001)· Abstract Source“Digitoxin is a cardiac glycoside that differs from digoxin through its hepatic clearance and more stable pharmacokinetics, diminishing the impact of renal dysfunction and serum concentration fluctuations, thereby improving safety and facilitating long-term use in routine care.”
Geavlete O, Ambrosy AP, et al. The DIGIT-HF trial and the Mihai Gheorghiade legacy: time to reconsider cardiac glycosides as effective therapy in HFrEF. Heart Fail Rev 2026 (PubMed abstract) (2026)· Abstract Source“Digoxin is eliminated predominantly by the kidneys, whereas digitoxin undergoes substantial enterohepatic circulation, enabling effective clearance even in cases of severe renal impairment and yielding more stable plasma concentrations (5).”
Wang D, et al. Cardiac glycosides in patients with heart failure and reduced ejection fraction: a systematic review and meta-analysis. Front Cardiovasc Med 2026 (PMC13021435) (2026)· Discussion Source“As digitoxin elimination is much less dependent on the kidney than digoxin, digitoxin may constitute a very helpful drug in elderly patients with HFrEF.”
de Boer RA, et al. Heart failure in the elderly: epidemiology, mechanisms, and management. Eur Heart J 2026 (PMC13286651) (2026)· Section 'Special considerations in elderly' Source“Digoxin has a shorter half-life and is highly dependent on renal elimination, features that increase the risk of toxicity in frail patients or those with renal impairment. In contrast, digitoxin has a longer half-life, higher protein binding, and predominantly hepatic elimination with enterohepatic recirculation, resulting in more stable plasma levels and a reduced need for monitoring.”
Sciatti E, et al. The comeback of digitalis (digitoxin): the DIGIT-HF trial. Eur Heart J Suppl 2026 (PMC13147277) (2026)· Introduction Source“0.05–0.1 mg/day (adjust to blood levels and CrCl)”
Merino JL, Tamargo J, et al. Practical compendium of antiarrhythmic drugs: a clinical consensus statement of the European Heart Rhythm Association of the ESC. Europace 2025 (PMC12367031) (2025)· Table 2 (Typical market formulations and dosing of commonly used AADs), digitoxin row, oral maintenance 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
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.
Digitoxin in advanced CKD (no renal adjustment vs exclusion of severe renal disease)
“Alleinige Störungen der Nierenfunktion haben kaum einen Einfluss auf die Elimination von Digitoxin, da die reduzierte renale Elimination durch vermehrte Metabolisierung und fäkale Elimination kompensiert wird.”
“Concomitant severe liver and renal disease”
Bavendiek U, et al. Rationale and design of the DIGIT-HF trial. Eur J Heart Fail 2019 (PMC6607489) (2019)· Table 2 Exclusion criteria Source“will only exclude patients with “severe renal disease” because digitoxin does not accumulate in patients with renal impairment.”
Beldhuis 2022 Circulation: Evidence-based medical therapy in HFrEF patients with CKD (2022)· p. 12 Source“Digitoxin recommended when eGFR is reduced”
Sciatti E, et al. The comeback of digitalis (digitoxin): the DIGIT-HF trial. Eur Heart J Suppl 2026 (PMC13147277) (2026)· Table 1 Source
Tool uses esc2026: ESC 2026 HF (p. 35) states hepatic elimination; matrix statuses follow digoxin (more restrictive, only FDA-approved agent) with a digitoxin note. Owner to decide whether to split the class into two drug rows for G4–dialysis. SmPC quote (German): isolated renal dysfunction hardly affects digitoxin elimination because metabolism and faecal elimination compensate.
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.