Digitalis (Digitalis purpurea and Related Species): A Comprehensive Reference
1. Identity: Botanical Names, Natural Sources, and Forms
Botanical and Common Names
Digitalis is a derivative of the plant Digitalis purpurea, commonly known as purple foxglove. The plant's name, Digitalis (from the Latin digit, meaning finger), describes the finger-shaped purple flowers it bears. Digitalis is a genus of approximately twenty species of flowers that grow wild in much of the eastern hemisphere; several species have been used medically for centuries and remain the source for digoxin, a drug still used to treat cardiac arrhythmia.
The active components of the foxglove — chiefly Digitalis purpurea and Digitalis lanata — are classified as cardiac glycosides or cardiotonic steroids and include the well-known digitalis leaf, digitoxin, and digoxin; ouabain is a rapid-acting glycoside usually obtained from Strophanthus gratus. Cardiac glycosides of medicinal importance have been obtained from Digitalis purpurea Linné (Scrophulariaceae) — yielding digitoxin, digitalis, and gitalin — and Digitalis lanata Ehrhart (Scrophulariaceae) — yielding digoxin, digitoxin, lanatoside C, deslanoside, and acetyldigitoxin. The term "digitalis" is sometimes used to designate the entire class of cardiac glycosides.
Natural Source and Plant Morphology
Digitalis purpurea is a biennial plant that grows about 3–6 feet tall. The leaves are a basal rosette, ovate to lance-shaped, soft, hairy, and toothed; the flowers are purple to white, spotted thimbles approximately 1¼ inches long on spikes. Digitalis, popularly known as foxglove, is a native plant of the mountainous regions of all western Europe; it is found from Portugal to Finland and from middle Germany down to Italy. Although originally grown in Europe, the plant was transplanted in America over 200 years ago.
Plant Part Used and Primary Forms
The leaves of the plant from the second year's growth are the source of the therapeutic digitalis glycosides digitoxin and digoxin. The seeds of D. purpurea contain different glycosides from those of the leaves. When extracted and standardized, they are known as "Digitalin" (Digitalinum Purum Germanicum or amorphous Digitalin), which consists of the physiologically active "digitalinum verum" with other water-soluble glycosides, including the saponins digitonin and gitonin. The most effective treatment form identified by early investigators was a powder made from dried leaves picked just before the plant blossomed.
In modern pharmaceutical use, digitalis-derived compounds are available in several forms. Digoxin tablets come in three different doses: 62.5 mcg, 125 mcg, and 250 mcg; the oral liquid comes in a concentration of 50 mcg/mL; and intravenous (IV) injection is usually only given in a hospital or medical office. Digoxin injection is frequently used to achieve rapid digitalization, with conversion to digoxin tablets or digoxin solution in capsules for maintenance therapy.
2. Traditional and Historical Use
Ancient and Medieval Use
The earliest use of foxglove can be traced back to the Greek and Roman eras, based on reports that the "father of pharmacognosy," Pedanius Dioscorides, was aware of its effects. In Welsh and Irish folklore, foxglove was considered to protect against the evil eye and witchcraft. Digitalis, derived from the foxglove plant, garnered early mentions in medical writings as far back as 1250 by the Welsh family of physicians known as the Physicians of Myddvai, who included it in their prescriptions.
Its medicinal virtues do not seem to have been known to the ancient writers of Greece and Rome; northern people appear to have first discovered its remedial powers, and its use originally was only for external purposes, as evidenced by a treatise of the thirteenth century on the practice of medicine in Wales, Great Britain. Its utilization remained sporadic until the 18th century, when William Withering, an esteemed English physician and botanist, significantly contributed to its understanding and medical application.
William Withering and the Systematization of Foxglove Medicine
English physician William Withering (1741–1799), who experimented with the extract in fowls and humans, first observed the effects of the plant extract on the heart in the late eighteenth century. Withering noted that old country women used foxglove to treat dropsy (edema), an accumulation of fluids caused by a failing heart. Willing to consider these folk remedies, Withering embarked on a detailed study of digitalis; he determined the most effective treatment form — a powder made from dried leaves picked just before the plant blossomed — and, of critical importance, the correct dosage for different cardiac conditions. The medical use of digitalis was popularized by his book, An Account of the Foxglove, first published in 1785.
Although used as a heart drug today, Withering used digitalis for a wide variety of ailments, including anasarca (generalized edema), epilepsy, and hydrothorax (fluid in the pleural cavity). Initially, foxglove was considered a sedative on the nervous and arterial system with diuretic properties and was spoken of as a tonic to the heart and arteries. According to the 1883 edition of the Therapeutic Handbook of the United States Pharmacopoeia, digitalis primarily influences the heart and arteries; in small doses it reduces the frequency and increases the force of the heart's beat, rendering the pulse slower and firmer. The indications for its use are most frequently met in valvular disease, but it may be of value in almost any instance where the beat is feeble and irregular and the circulation is sluggish.
Its value was long doubted by physicians, and as late as the last quarter of the eighteenth century Murray spoke of foxglove as a doubtful remedy; but in 1775 Withering published his experience with this plant in the treatment of dropsy, which may be looked upon as the beginning of its career in scientific medicine. Through Thileus, digitalis became known to the Germans, whence its reputation began to spread over the rest of the Continent.
Van Gogh and the Cultural Footprint of Digitalis
Visual aberrations caused by digitalis include a tipping of the color scale toward yellow (xanthopsia), and halos around bright points of light. Such effects are displayed in some of the later works of Vincent van Gogh, his "yellow period." Halos around the stars and moon are evident in his famous painting "The Starry Night" and other works. It has been theorized that these effects are due to his use of foxglove to treat epilepsy, suggested by several self-portraits which included depictions of foxglove as well as two paintings of his doctor, which show him holding sprays of the flower.
3. Key Chemical Constituents and Active Compounds
Primary Glycosides
The primary (tetra) glycosides of D. purpurea — purpurea glycoside A, purpurea glycoside B, and glucogitaloxin — all possess at C-3 of the genin a linear chain of three digitoxose sugar moieties terminated by glucose. Purpurea glycosides A and B, first characterized by A. Stoll in 1938, constitute the principal active constituents of the fresh leaves. On drying, enzyme degradation takes place with the loss of the terminal glucose to give digitoxin, gitoxin, and gitaloxin, respectively; digitoxin and gitoxin are therefore the main active components of the dried drug.
The main chemical constituents of digitalis are primary and secondary glycosides, present in amounts of approximately 0.2–0.45%. Purpurea glycosides A and B and glucogitaloxin are the primary glycosides; digitoxin, gitoxin, and gitaloxin are the secondary glycosides present in digitalis. The total number of glycosides reported in the drug is approximately 30.
Additional Constituents
The seeds also contain digitalis glycosides, while steroidal saponins, flavones, the flavonoid chrysoeriol, anthraquinones, and organic acids have been identified in the leaves. The leaves of Digitalis purpurea also contain anthraquinone derivatives, including 1-methoxy-2-methylanthraquinone, 3-methoxy-2-methylanthraquinone, digitolutein (3-methylalizarin-1-methylether), 3-methylalizarin, and 1,4,8-trihydroxy-2-methyl-anthraquinone. The important saponins include digitonin, tigonin, and gitonin, and luteolin, a flavone responsible for the colour of the drug. Digitalis purpurea also contains volatile oil, fatty matter, starch, gum, and sugars.
The Primary Pharmaceutical Derivative: Digoxin
Digoxin, a cardiac glycoside derived from the foxglove plant (Digitalis spp.), has been utilized for centuries in managing various cardiac conditions due to its ability to increase myocardial contractility and regulate heart rate. Digoxin, a widely prescribed cardiac glycoside, is listed as an essential medicine by the World Health Organization and is one of the most prescribed naturally derived pharmaceutical products. Isolated digitoxin is 1,000 times more potent than whole powdered leaves and is completely and rapidly absorbed from the GI tract.
4. Mechanisms of Action
Inhibition of Na⁺/K⁺-ATPase
These drugs are potent inhibitors of cellular membrane sodium-potassium adenosine triphosphatase (Na⁺/K⁺-ATPase). The primary mechanism of action of digitalis is the inhibition of the sodium-potassium ATPase pump within the myocyte. This reversible inhibition of the ATPase results in increased intracellular sodium levels. The build-up of intracellular sodium leads to a shift of sodium extracellularly through another channel in exchange for calcium ions — this influx of intracellular calcium results in increased myocyte contractility.
In the heart, increased intracellular calcium causes more calcium to be taken up and subsequently released by the sarcoplasmic reticulum, thereby making more calcium available to bind to troponin-C, which increases contractility (inotropy). Inhibition of the Na⁺/K⁺-ATPase in vascular smooth muscle causes depolarization, which causes smooth muscle contraction and vasoconstriction.
Autonomic and Neurohormonal Effects
By mechanisms that are not fully understood, digitalis compounds also increase vagal efferent activity to the heart. This parasympathomimetic action of digitalis reduces sinoatrial firing rate (negative chronotropy) and reduces conduction velocity of electrical impulses through the atrioventricular node (negative dromotropy). In parallel, digitalis exerts important neurohormonal actions by reducing sympathetic activation and activity of the renin–angiotensin–aldosterone system. The overall effect is improved contractile performance, reduced congestion, and symptomatic improvement in patients with heart failure.
Structural Variation and Pharmacokinetics
The differences in the lactone ring and sugar moiety among the various cardiac glycosides lead to changes in toxicokinetics, clinical signs, and potential for arrhythmias. Despite the fact that the molecular target for the cardiac glycosides — the α-subunit of sarcolemmal Na⁺K⁺-ATPase (the sodium pump), found on most eukaryotic cell membranes — has been known for several decades, it remains controversial whether the sympatholytic or positive inotropic effects of these agents is the mechanism most relevant to relief of heart failure symptoms in humans with systolic ventricular dysfunction.
5. Scientific Evidence by Area of Use
5a. Heart Failure
Digitalis glycosides have been used clinically for the treatment of heart failure for more than 200 years and remain the source of commercial digoxin preparations; however, a defined place in therapy remains under debate.
The Digitalis Investigation Group (DIG) Trial
In 1997, the Digitalis Investigation Group (DIG) trial — a large placebo-controlled study in patients with heart failure in sinus rhythm — demonstrated that digoxin, when added to diuretics and angiotensin-converting enzyme inhibitors, did not reduce all-cause mortality (its primary endpoint), but was associated with a significant 28% reduction in hospitalization for worsening heart failure. Specifically, there were 1,181 deaths (34.8%) with digoxin and 1,194 deaths (35.1%) with placebo (risk ratio 0.99; 95% confidence interval, 0.91 to 1.07; P = 0.80).
Despite these findings, digoxin use subsequently declined for several reasons, in particular the introduction of other effective drugs and devices for heart failure, as well as numerous post hoc analyses suggesting that digoxin use was associated with unfavorable outcomes, often due to prescription bias.
Post hoc analyses of the DIG trial produced nuanced findings related to serum concentrations. Later analyses from DIG showed that lower serum digoxin levels were associated with a favourable effect, while higher digoxin levels worsened prognosis. Data from post hoc analyses of the DIG trial suggest that digoxin reduces mortality at low (0.5–0.9 ng/ml) serum digoxin concentrations (SDC), but had no effect at higher (≥1 ng/ml) SDC.
PROVED and RADIANCE Trials
The results of the DIG trial, together with those of earlier randomized controlled trials such as PROVED (Prospective Randomized Study of Ventricular Failure and the Efficacy of Digoxin) and RADIANCE (Randomized Assessment of the Effect of Digoxin on Inhibitors of the Angiotensin-Converting Enzyme) — in which the favorable effects of digoxin, including reduction in symptoms, improvement in NYHA functional class and exercise time, and reduction in hospitalizations, were lost after drug withdrawal — were used by the US Food and Drug Administration (FDA) in 1997 to approve digoxin for the treatment of heart failure.
The DIGIT-HF Trial (2025)
The DIGIT-HF (Digitoxin to Improve Outcomes in Patients With Advanced Chronic Heart Failure; N Engl J Med 2025) trial compared digitoxin with placebo, added to guideline-directed medical therapy in patients with heart failure with reduced ejection fraction (HFrEF). Compared with placebo, digitoxin reduced the incidence of the composite endpoint of death from any cause or first hospitalization for worsening heart failure by 18% over a median follow-up of 36 months (hazard ratio 0.82, 95% confidence interval 0.69–0.98). There were no statistically significant differences in the rates of all-cause mortality, first hospitalization, or serious adverse events.
DECISION Trial and Updated Meta-Analysis (2026)
Investigators at the University Medical Center Groningen, Netherlands, evaluated the effects of digoxin and digitoxin in patients with heart failure with reduced or mildly reduced left ventricular ejection fraction (HF(m)rEF). "Digoxin is the oldest drug in cardiovascular medicine, but there has been uncertainty about its value in HF(m)rEF management," explained principal investigator Professor Dirk van Veldhuisen. "In the DIG trial, published in 1997, digoxin had a neutral effect on the primary endpoint of mortality, but a 28% reduction in heart failure hospitalisations (a secondary endpoint) was observed."
A meta-analysis of the DECISION, DIGIT-HF, and DIG trials, across 9,013 patients, found that digitalis glycoside treatment reduced the risk of the primary endpoint of time to cardiovascular death or first worsening heart failure event compared with placebo (HR 0.85; 95% CI 0.80 to 0.90; p<0.001). This reduction was mostly attributable to the effect on time to the first worsening heart failure event (HR 0.75; 95% CI 0.69 to 0.81; p<0.001). There was no statistically significant heterogeneity by trial, treatment period, or type of digitalis glycoside.
Diastolic Heart Failure
In the Digitalis Investigation Group ancillary trial, ambulatory chronic heart failure patients (n=988) with normal sinus rhythm and ejection fraction >45% (median, 53%) from the United States and Canada were randomly assigned to digoxin (n=492) or placebo (n=496). At follow-up with a mean length of 37 months, the primary outcome of HF hospitalization or HF mortality showed a nonsignificant 18% lower risk in patients receiving digoxin. This evidence is considered weak and inconclusive for this population.
5b. Atrial Fibrillation (AF) and Rate Control
While β-blockers and non-dihydropyridine calcium-channel blockers remain first-line agents for both acute and chronic rate control in AF, digoxin is still a therapeutic option, particularly in older adults, in patients with hypotension, and in those with coexisting heart failure with reduced ejection fraction (HFrEF). In the treatment of arrhythmia, digitalis modulates the ventricular rate by stimulating the release of acetylcholine, thus increasing cardiac vagal nerve activity.
Meta-analyses on acute heart rate control (within 6 hours of treatment onset) showed firm evidence of digoxin being superior compared with placebo (mean difference −12.0 beats per minute; TSA-adjusted CI, −17.2 to −6.76) and inferior compared with beta blockers (mean difference 20.7 bpm; TSA-adjusted CI, 14.2 to 27.2). Meta-analyses also showed digoxin to be inferior compared with both calcium antagonists and amiodarone, though trials comparing those agents lacked sufficient information in trial sequential analyses.
In the RATE-AF randomized clinical trial — which provided the first modern head-to-head comparison — there was little prior evidence to support selection of heart rate control therapy in patients with permanent AF with coexisting heart failure. Among patients treated with low-dose digoxin or bisoprolol, there was no statistically significant difference in quality of life at 6 months, suggesting decisions about treatment may be based on other endpoints.
Several observational analyses, post hoc analyses from clinical trials, registries, and meta-analyses have been published addressing digoxin in AF. These studies have provided conflicting results, possibly due to varying patient populations and analytical methods. A nationwide nested case–control analysis suggested that the "mortality signal" is unlikely to be causal, noting parallel associations with non-cardiac outcomes consistent with digoxin being a marker of clinical vulnerability rather than a mediator of harm. Across datasets, low serum digoxin concentrations were consistently associated with stable resting rate control without increasing mortality.
5c. Anticancer Potential
A considerable number of in vitro and in vivo studies since the 1960s discuss a potential therapeutic benefit of digitalis glycosides on neoplastic cells due to antiproliferative effects by targeting various pathways. The discussion was initiated by the sporadic observation of reduced malignancies in patients treated with digitalis. The potential anticancer effects of cardiac glycosides garnered attention in 1979 when Stenkvist et al. reported lower severity and metastasis of breast cancer in users of cardiac glycosides compared with non-users.
Pre-clinical studies have identified several mechanisms for anti-tumor activities of cardiac glycosides. The main mechanism is inhibiting Na⁺/K⁺-ATPase activity, which increases intracellular Ca²⁺ leading to apoptosis of tumor cells. Other studies found that digitalis activates Src kinase and Cdk5/p25 pathways. Digoxin could also inhibit the synthesis of HIF-1α protein and the expression of the HIF-1 gene, which decreased the growth of tumor xenografts.
In addition to its ability to inhibit cellular proliferation, digitalis can cause death of malignant cells. Several cardiac glycosides have been shown to induce apoptosis in a variety of cancer cell lines, including renal adenocarcinoma, melanoma, breast adenocarcinoma, and leukemia. More recent evidence also demonstrates that cardiac glycosides can cause cell death by autophagy.
Retrospective clinical data indicate that cardiac glycosides, notably digoxin, prolong the survival of carcinoma patients treated with conventional chemotherapy. Cardiac glycosides are known to influence the immune response at multiple levels. In addition, recent results suggest that cardiac glycosides trigger the immunogenic demise of cancer cells, an effect that most likely contributes to their clinical anticancer activity.
Although some preclinical studies almost unanimously demonstrated an anti-cancer effect of digitalis glycosides, some clinical studies revealed opposing effects suggesting a certain carcinogenic potential of digitalis glycosides under certain conditions. The anticancer mechanism of digitoxin or synthetic analogs is still subject to study while concerns about digitoxin's cardiotoxicity preclude its clinical application in cancer therapeutics. Evidence in this area remains preliminary and largely preclinical; no digitalis-derived compound has been approved as a cancer therapeutic in Western medicine.
5d. Other Investigated Areas (Preliminary Evidence Only)
A study in hyperglycemic and dyslipidemic rats demonstrated enhanced glucose tolerance two hours after the rats were given a single dose of the saponin digitonin. Positive effects on the lipid profile were also observed. This evidence is animal-only and has not been established in humans.
Antileishmanial activity has been demonstrated in mice with the administration of beta-acetyl-digitoxin extracted from D. lanata leaves. Again, this evidence is entirely preclinical.
Recent studies have expanded the medical applications of cardiac glycosides to include investigation of their potential role in the treatment of viral infections, inflammation, cancer, hypertension, and neurodegenerative diseases, with a significant portion of the cancer treatment effects attributed to the modulation of signal transduction pathways via the inhibition of Na⁺/K⁺-ATPase. None of these additional areas have robust clinical trial support.
6. Body Systems and Health Areas of Association
- Cardiovascular system: Cardiac glycosides exert their main effect through reversible inhibition of the Na⁺/K⁺-ATPase on the myocardial cell membrane, resulting in positive inotropy, reduced congestion, and symptomatic improvement in patients with heart failure.
- Electrophysiology / cardiac conduction: Digoxin directly affects conduction through increased vagal tone, which leads to decreased chronotropy.
- Renal: Digoxin is mainly excreted by the kidneys unchanged. A steady-state plateau is achieved in patients with normal renal function in 7 to 10 days; the elimination half-life is 1.5 to 2 days, but can be as long as a week in patients with renal insufficiency and end-stage renal disease.
- Neurohormonal / autonomic nervous system: Digitalis exerts important neurohormonal actions by reducing sympathetic activation and activity of the renin–angiotensin–aldosterone system.
- Oncology (investigational): An increasing number of research studies reveal that cardiac glycosides exhibit selective anti-proliferative and pro-apoptosis effects against various human cancer cell lines, including cervical, lymphoma, lung, colon, breast, prostate, melanoma, pancreas, and liver cancer cell lines.
7. Dosage Forms and Dosages Reported in Studies
Oral Preparations
The doses of digoxin used in controlled trials in patients with heart failure have ranged from 125 to 500 mcg (0.125 to 0.5 mg) once daily.
A single initial (loading) dose of 500 to 750 mcg (0.5 to 0.75 mg) of digoxin tablets usually produces a detectable effect in 0.5 to 2 hours that becomes maximal in 2 to 6 hours. Additional doses of 125 to 375 mcg (0.125 to 0.375 mg) may be given cautiously at 6 to 8-hour intervals until clinical evidence of an adequate effect is noted.
The usual amount of digoxin tablets that a 70 kg patient requires to achieve 8 to 12 mcg/kg peak body stores is 750 to 1,250 mcg (0.75 to 1.25 mg).
Intravenous Administration
Digoxin injection is frequently used to achieve rapid digitalization, with conversion to digoxin tablets or oral solution for maintenance therapy. When changing from parenteral to oral dose forms, dose adjustments may be necessary because of pharmacokinetic variations in percentage of digoxin absorbed: 100 mcg (0.1 mg) digoxin injection is equivalent to 125 mcg (0.125 mg) tablet or 125 mcg (0.125 mg) of elixir.
Therapeutic Serum Concentration Range
Because the mechanism of action of the cardiac glycosides relevant to their beneficial effects in heart failure patients remains controversial, there is debate about the appropriate therapeutic range for digoxin. Based on clinical trial data, this range has been placed between 0.5 and 1.5 ng/mL. A post hoc analysis of the DIG trial suggested that the serum digoxin concentration was directly related to mortality, with reduced mortality among patients with low digoxin levels (between 0.5 and 0.8 ng/ml) and increased mortality among patients with levels >1.1 ng/ml.
Pediatric Dosing
Reported pediatric digitalizing (loading) doses range broadly by age group: for premature neonates, oral elixir 20 to 30 mcg/kg and IV 15 to 25 mcg/kg; for full-term neonates, oral elixir 25 to 35 mcg/kg and IV 20 to 30 mcg/kg; for children aged 1 to 24 months, oral elixir 35 to 60 mcg/kg and IV 30 to 50 mcg/kg; for children aged 3 to 5 years, oral elixir 30 to 40 mcg/kg and IV 25 to 35 mcg/kg.
8. Safety Considerations and Drug Interactions
Narrow Therapeutic Index
Digoxin has a narrow therapeutic index, and its administration is influenced by drug-drug interactions and comorbidities. Digitoxin, digoxin, and several other cardiac glycosides have steep dose-response curves — minute increases in the dosage of these drugs can make the difference between an ineffective dose and a fatal one.
The well-defined toxicity and narrow therapeutic window due to the gross inhibition of the Na⁺/K⁺-ATPase has caused digoxin to lose favor as a stand-alone inotrope.
Toxicity: Clinical Presentation
Risk factors for toxicity include low body weight, advanced age, impaired renal function, hypokalemia, hypomagnesemia, hypercalcemia, and drug interactions such as amiodarone, verapamil, macrolides, and diuretics. The overall incidence of adverse reactions is 5–20%, with 15–20% considered serious. Digoxin toxicity typically presents with early gastrointestinal symptoms (nausea, vomiting, anorexia), neurologic changes (headache, confusion, dizziness), and arrhythmias such as AV block, atrial tachycardia with block, AV dissociation, ventricular premature contractions, and ventricular tachycardia/fibrillation.
An overdose of digoxin can lead to severe arrhythmias and malignant hyperkalemia. Changes on the ECG typical of digoxin toxicity can include down-sloping ST segment depression ("scooped out" or "reverse tick" appearance), flattened/inverted T waves, and increased U wave amplitude.
Renal Function
Digoxin is eliminated primarily in the urine, and many cases of chronic digoxin toxicity occur in the context of declining renal function. The clearance of digoxin is closely tied to the glomerular filtration rate (GFR), which suggests that the safety and efficacy of digoxin may vary with renal function. In patients with renal dysfunction, the elimination half-life of digoxin is prolonged, and systemic exposure is increased.
Electrolyte Interactions
Electrolyte disturbances, including hypomagnesemia, hypercalcemia, and hypokalemia, lead to increased sensitivity to digoxin, making toxicity more likely even at a lower concentration of serum digoxin. In patients with hypokalemia or hypomagnesemia, toxicity may occur despite serum digoxin concentrations below 2 ng/mL, because potassium or magnesium depletion sensitizes the myocardium to digoxin. It is therefore desirable to maintain normal serum potassium and magnesium concentrations in patients being treated with digoxin. Calcium, particularly when administered rapidly by the IV route, may produce serious arrhythmias in digitalized patients.
Drug–Drug Interactions
Digoxin has significant drug-to-drug interactions with a host of medications, but notably with amiodarone and verapamil, because both decrease its metabolism and can result in elevated levels of digoxin. Quinidine reduces both the renal and nonrenal elimination of digoxin and also decreases its volume of distribution; recent evidence indicates that quinidine inhibits digoxin transport across epithelial cell membranes (particularly in the kidney) owing to its high affinity for P-glycoprotein. Amiodarone administration has also been found to increase the steady-state digoxin concentration. Studies have found that a high proportion of patients exposed to a digoxin–diuretic interaction have reduced serum potassium and/or magnesium concentrations, and an increased occurrence of cardiac arrhythmia has been noted; changes in electrolyte concentrations, especially potassium, are considered to be the main mechanism accounting for adverse clinical outcomes caused by digoxin–diuretic interactions.
Special Populations
Digoxin concentrations in breast milk are low, resulting in minimal infant exposure and a low likelihood of adverse effects; to further reduce exposure, it is recommended to delay breastfeeding for at least 2 hours after IV administration of digoxin. The safety and efficacy of digoxin for ventricular rate control in children with atrial fibrillation remain insufficiently established.
A hypersensitivity reaction to other digitalis preparations usually constitutes a contraindication to digoxin. Because digoxin slows sinoatrial and AV conduction, the drug commonly prolongs the PR interval. The drug may cause severe sinus bradycardia or sinoatrial block in patients with pre-existing sinus node disease and may cause advanced or complete heart block in patients with pre-existing incomplete AV block.
Antidote for Toxicity
Treatment with digoxin immune Fab (trade name Digibind) is considered first-line therapy for dysrhythmias, including AV block and ventricular tachycardia, caused by suspected digoxin toxicity. Fab fragments are highly effective in binding the digoxin molecule with minimal detrimental adverse effects. Empiric treatment of acute toxicity consists of 10 vials of Fab fragments for adults and 5 vials for children when the dose ingested is unknown and digoxin levels cannot be obtained.
References
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