indication

For the treatment and management of congestive cardiac insufficiency, arrhythmias and heart failure.

pharmacology

Digoxin, a cardiac glycoside similar to digitoxin, is used to treat congestive heart failure and supraventricular arrhythmias due to reentry mechanisms, and to control ventricular rate in the treatment of chronic atrial fibrillation.

mechanism of action

Digoxin inhibits the Na-K-ATPase membrane pump, resulting in an increase in intracellular sodium. The sodium calcium exchanger (NCX)in turn tries to extrude the sodium and in so doing, pumps in more calcium. Increased intracellular concentrations of calcium may promote activation of contractile proteins (e.g., actin, myosin). Digoxin also acts on the electrical activity of the heart, increasing the slope of phase 4 depolarization, shortening the action potential duration, and decreasing the maximal diastolic potential.

toxicity

Toxicity includes ventricular tachycardia or ventricular fibrillation, or progressive bradyarrhythmias, or heart block. LD₅₀ = 7.8 mg/kg (orally in mice).

biotransformation

Hepatic (but not dependent upon the cytochrome P-450 system). The end metabolites, which include 3 b-digoxigenin, 3-keto-digoxigenin, and their glucuronide and sulfate conjugates, are polar in nature and are postulated to be formed via hydrolysis, oxidation, and conjugation.

absorption

Absorption of digoxin from the elixir pediatric formulation has been demonstrated to be 70% to 85% complete (90% to 100% from the capsules, and 60% to 80% for tablets).

half life

3.5 to 5 days

route of elimination

Following intravenous administration to healthy volunteers, 50% to 70% of a digoxin dose is excreted unchanged in the urine.

drug interactions

Acarbose: Acarbose may decrease the serum levels of digoin. It is thought that acarbose reduces digoin absorption. Monitor for changes in digoxin serum levels and therapeutic and adverse effects if acarbose is initiated, discontinued or dose changed.

Alprazolam: The benzodiazepine, alprazolam, may increase the effect of digoxin.

Amiodarone: Amiodarone may increase the effect of digoxin.

Bendroflumethiazide: Possible electrolyte variations and arrhythmias

Benzthiazide: Possible electrolyte variations and arrhythmias

Bleomycin: The antineoplasic agent decreases the effect of digoxin

Bumetanide: Possible electrolyte variations and arrhythmias

Carmustine: The antineoplasic agent decreases the effect of digoxin

Carvedilol: Carvedilol may increase the serum levels and effect of digoxin.

Chlorothiazide: Possible electrolyte variations and arrhythmias

Chlorthalidone: Possible electrolyte variations and arrhythmias

Cholestyramine: The resin decreases the effect of digoxin

Cinitapride: Cinitapride can alter the absorption of digoxin as it simulates gastric emptying.

Clarithromycin: The macrolide, clarithromycin, may increase the effect of digoxin in 10% of patients.

Colestipol: The resin decreases the effect of digoxin

Cyclophosphamide: The antineoplasic agent decreases the effect of digoxin

Cyclosporine: Cyclosporine may increase the effect of digoxin.

Cyclothiazide: Possible electrolyte variations and arrhythmias

Cytarabine: The antineoplasic agent decreases the effect of digoxin

Dextrothyroxine: The thyroid hormone, dextrothyroxine, decreases the effect of digoxin.

Diazepam: The benzodiazepine, diazepam, may increase the effect of digoxin.

Dihydroquinidine barbiturate: Quinine/quinidine increases the effect of digoxin

Doxorubicin: The antineoplasic agent decreases the effect of digoxin

Erythromycin: The macrolide, erythromycin, may increase the effect of digoxin in 10% of patients.

Ethacrynic acid: Possible electrolyte variations and arrhythmias

Furosemide: Possible electrolyte variations and arrhythmias

Gatifloxacin: Gatifloxacin increases the effect of digoxin

Ginseng: Changes in digoxin serum levels

Hydrochlorothiazide: Possible electrolyte variations and arrhythmias

Hydroflumethiazide: Possible electrolyte variations and arrhythmias

Hydroxychloroquine: Hydroxychloroquine increases the effect of digoxin

Indapamide: Possible electrolyte variations and arrhythmias

Itraconazole: Itraconazole increases the effect of digoxin

Josamycin: The macrolide, josamycin, may increase the effect of digoxin in 10% of patients.

Levothyroxine: The thyroid hormone, levothyroxine, decreases the effect of digoxin.

Liothyronine: The thyroid hormone, liothyronine, decreases the effect of digoxin.

Liotrix: The thyroid hormone, liotrix, decreases the effect of digoxin.

Methimazole: The antithyroid agent increases the effect of digoxin

Methotrexate: The antineoplasic agent decreases the effect of digoxin

Methyclothiazide: Possible electrolyte variations and arrhythmias

Metolazone: Possible electrolyte variations and arrhythmias

Penciclovir: The multivalent agent decreases the effect of penicillamine

Penicillamine: Penicillamine decreases the effect of digoxin

Polythiazide: Possible electrolyte variations and arrhythmias

Prazosin: Prazosin increases the effect of digoxin

Procarbazine: The antineoplasic agent decreases the effect of digoxin

Propafenone: Propafenone increases the effect of digoxin

Propylthiouracil: The antithyroid agent may increase the effect of digoxin.

Quinethazone: Possible electrolyte variations and arrhythmias

Quinidine: Quinine/quinidine increases the effect of digoxin

Quinidine barbiturate: Quinine/quinidine increases the effect of digoxin

Quinine: Quinine/quinidine increases the effect of digoxin

Rabeprazole: Rabeprazole increases the effect of digoxin

Ranolazine: Ranolazine may increase the serum level of digoxin. Monitor for changes in the serum level and therapeutic and adverse effects of digoxin if ranolazine is initiated, discontinued or dose changed.

Ritonavir: Ritonavir increases levels/effect of digoxin

Spironolactone: Increased digoxin levels and decreased effect in presence of spironolactone

St. John's Wort: St. John's Wort decreases the effect of digoxin

Sulfasalazine: Sulfasalazine may decrease the effect of digoxin.

Telithromycin: Telithromycin may increase the plasma concentration of Digoxin. Monitor for changes in Digoxin efficacy/toxicity if Telithromycin is initiated, discontinued or dose changed.

Telmisartan: Telmisartan may increase plasma Digoxin concentrations. Monitor Digoxin levels and adjust dose as required if Telmisartan is initiated, discontinued or dose changed.

Thyroglobulin: The thyroid hormone, thyroglobulin, decreases the effect of digoxin.

Ticlopidine: Ticlopidine may decrease Digoxin levels. Monitor for Digoxin levels with Ticlopidine is initiated, discontinued or dose changed.

Tolbutamide: Tolbutamide increases the effect of digoxin

Trichlormethiazide: Possible electrolyte variations and arrhythmias

Trimetrexate: The absorption of Digoxin, a cardiac glycoside, may be decreased by antineoplastic agents such as Trimetrexate. Liquid forms of Digoxin do not appear to be significantly affected. Monitor Digoxin tablet efficacy if Trimetrexate therapy is initiated, discontinued or if the dose is altered.

Verapamil: Verapamil may increase the serum concentration of Digoxin by decreasing its metabolism and clearance. Monitor for changes in the therapeutic/adverse effects of Digoxin if Verpamail is initiated, discontinued or dose changed.

Vincristine: The antineoplasic agent decreases the effect of digoxin

Voriconazole: Voriconazole may increase the serum concentration of digoxin. Monitor for increased serum concentrations and toxic effects of digoxin if voriconazole is initiated or dose increased.