CHF and arrhythmias:

Indications for: LANOXIN INJECTION

Mild-to-moderate heart failure (with a diuretic and an ACE inhibitor when possible). Increase myocardial contractility in pediatrics with heart failure. Control of ventricular response rate in chronic atrial fibrillation.

Clinical Trials:

Chronic Heart Failure

Lanoxin was evaluated in two 12-week, double-blind, placebo-controlled studies enrolled 178 (RADIANCE trial) and 88 (PROVED trial) adult patients with NYHA Class II or III heart failure previously treated with oral digoxin, a diuretic, and an ACE inhibitor (RADIANCE only). In both trials, patients who received Lanoxin demonstrated better preservation of exercise capacity. Patients who continued treatment with Lanoxin experienced a risk reduction in developing worsening heart failure, as evidenced by heart failure-related hospitalizations and emergency care and the need for concomitant heart failure therapy. 

DIG Trial of Lanoxin in Patients with Heart Failure

The 37-week, multicenter, randomized, double-blind, Digitalis Investigation Group (DIG) trial compared digoxin to placebo in 6800 adults with heart failure and left ventricular ejection fraction less than or equal to 0.45. As in the smaller trials described above, patients who had been receiving open-label digoxin were withdrawn from this treatment before randomization. 

Patients who were randomized to digoxin was 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%). On the other hand, there was no apparent effect on mortality (RR 99%, with confidence limits of 91-107%) for patients randomized to digoxin. 

 

Chronic Atrial Fibrillation

Digoxin has also been studied as a means of controlling the ventricular response to chronic atrial fibrillation in adults. Digoxin reduced the resting heart rate, but not the heart rate during exercise. 

The effects of digoxin were compared to placebo in 3 different randomized, double-blind trials that included a total of 315 adult patients for the conversion of recent-onset atrial fibrillation to sinus rhythm. The incidence of conversion in the digoxin and placebo treatment arms were equally likely and equally rapid.

In a randomized 120-patient trial, patients who received digoxin had the lowest incidence of conversion to sinus rhythm, and the least satisfactory rate control when conversion did not occur compared with sotalol and amiodarone.

In a randomized, double-blind, 43-patient crossover study, digoxin was studied as a means of delaying reversion to atrial fibrillation in adult patients with frequent recurrence of this arrhythmia. Findings showed that digoxin increased the  mean time between symptomatic recurrent episodes by 54%, but had no effect on the frequency of fibrillatory episodes seen during continuous electrocardiographic monitoring. 

Adults and Children:

Individualize: see full labeling. Reduce dose in premature and immature infants. Children usually need proportionally larger doses (based on body weight or surface area) than adults. Use divided doses for children <10yrs. Retitrate when changing formulations (esp. oral tabs to or from other dose forms).

LANOXIN INJECTION Contraindications:

Ventricular fibrillation.

LANOXIN INJECTION Warnings/Precautions:

Renal dysfunction: reduce dose. Sinus node disease. Incomplete AV block. Accessory AV pathway (Wolff-Parkinson-White syndrome). Heart failure with preserved LV ejection fraction (eg, restrictive cardiomyopathy, constrictive pericarditis, amyloid heart disease, acute cor pulmonale, idiopathic hypertrophic subaortic stenosis). Electrical cardioversion. Acute MI. Avoid in myocarditis. Toxicity risk increased by hypokalemia, hypomagnesemia, hypercalcemia. Hypocalcemia may nullify effects. Thyroid disease. Hypermetabolic states. Monitor digoxin levels, electrolytes, renal function. Premature infants. Neonates. Labor & Delivery. Pregnancy; monitor. Nursing mothers.

LANOXIN INJECTION Classification:

Cardiac glycoside.

LANOXIN INJECTION Interactions:

Toxicity risk increased by potassium-depleting drugs (eg, diuretics, amphotericin B, corticosteroids). Digoxin levels increased by antibiotics (eg, macrolides, tetracyclines), amiodarone, dronedarone, propafenone, quinidine, quinine, ritonavir, verapamil, indomethacin, itraconazole, lapatinib, mirabegron, spironolactone, telaprevir, drugs that reduce GI motility (eg, propantheline, diphenoxylate), thyroid antagonists, drugs that reduce renal function, others. Digoxin levels decreased by thyroid hormones, antacids, kaolin-pectin, cholestyramine, neomycin, penicillamine, rifampin, sulfasalazine, drugs that increase GI motility (eg, metoclopramide), certain antineoplastics, others. Digoxin levels possibly affected by alprazolam, cyclosporine, diclofenac, others. Arrhythmias with sympathomimetics, succinylcholine, or rapid calcium infusion. Heart block with drugs that affect cardiac conduction (eg, calcium channel blockers, β-blockers). Increased risk of bradycardia with ivabradine.

Adverse Reactions:

GI upset, anorexia, CNS effects (eg, blurred or yellow vision, or mental disturbances, confusion, headache, weakness, dizziness, apathy), gynecomastia, rash, heart block, arrhythmias (esp. children).

Metabolism:

Only a small percentage (13%) of a dose of digoxin is metabolized in healthy volunteers. The urinary metabolites, which include dihydrodigoxin, digoxigenin bisdigitoxoside, and their glucuronide and sulfate conjugates are polar in nature and are postulated to be formed via hydrolysis, oxidation, and conjugation.

Drug Elimination:

Elimination of digoxin follows first-order kinetics (that is, the quantity of digoxin eliminated at any time is proportional to the total body content). Following intravenous administration to healthy volunteers, 50-70% of a digoxin dose is excreted unchanged in the urine. Renal excretion of digoxin is proportional to creatinine clearance and is largely independent of urine flow. In healthy volunteers with normal renal function, digoxin has a half-life of 1.5-2 days. The half-life in anuric patients is prolonged to 3.5-5 days.

How Supplied:

Tabs—100, 1000; Inj 0.25mg/mL (2mL amps)—10; Inj Pediatric (1mL amp)—10