Digoxin Tablets

Name: Digoxin Tablets

Drug Interactions

Digoxin has a narrow therapeutic index, increased monitoring of serum digoxin concentrations and for potential signs and symptoms of clinical toxicity is necessary when initiating, adjusting, or discontinuing drugs that may interact with digoxin. Prescribers should consult the prescribing information of any drug which is co-prescribed with digoxin for potential drug interaction information.

P-Glycoprotein (PGP) Inducers/Inhibitors

Digoxin is a substrate of P-glycoprotein, at the level of intestinal absorption, renal tubular section and biliary-intestinal secretion. Therefore, drugs that induce/inhibit P-glycoprotein have the potential to alter digoxin pharmacokinetics.

Pharmacokinetic Drug Interactions

NA = Not available/reported

Digoxin concentrations increased greater than 50%

   Digoxin Serum   
Concentration Increase

   Digoxin AUC Increase

Recommendations

Amiodarone

70%

NA

Measure serum digoxin concentrations before initiating concomitant drugs. Reduce digoxin concentrations by decreasing dose by approximately 30-50% or by modifying the dosing frequency and continue monitoring.

Captopril

58%

39%

Clarithromycin

NA

70%

Dronedarone

NA

150%

Gentamicin

129-212%

NA

Erythromycin

100%

NA

Itraconazole

80%

NA

Lapatinib

NA

180%

Propafenone

NA

60-270%

Quinidine

100%

NA

Ranolazine

50%

NA

Ritonavir

NA

86%

Telaprevir

50%

85%

Tetracycline

100%

NA

Verapamil

50-75%

NA

Digoxin concentrations increased less than 50%

Atorvastatin

22%

15%

Measure serum digoxin concentrations before initiating concomitant drugs. Reduce digoxin concentrations by decreasing the dose by approximately 15-30% or by modifying the dosing frequency and continue monitoring.

Carvedilol

16%

14%

Conivaptan

33%

43%

Diltiazem

20%

NA

Indomethacin

40%

NA

Nefazodone

27%

15%

Nifedipine

45%

NA

Propantheline

24%

24%

Quinine

NA

33%

Rabeprazole

29%

19%

Saquinavir

27%

49%

Spironolactone     

25%

NA

Telmisartan

20-49%

NA

Ticagrelor

31%

28%

Tolvaptan

30%

20%

Trimethoprim

22-28%

NA

Digoxin concentrations increased, but magnitude is unclear

Alprazolam, azithromycin, cyclosporine, diclofenac, diphenoxylate, epoprostenol, esomeprazole, ibuprofen, ketoconazole, lansoprazole, metformin, omeprazole

Measure serum digoxin concentrations before initiating concomitant drugs. Continue monitoring and reduce digoxin dose as necessary.

Digoxin concentrations decreased

Acarbose, activated charcoal, albuterol, antacids, certain cancer chemotherapy or radiation therapy, cholestyramine, colestipol, extenatide, kaolin-pectin, meals high in bran, metoclopramide, miglitol, neomycin, penicillamine, phenytoin, rifampin, St. John’s Wort, sucralfate and sulfasalazine

Measure serum digoxin concentrations before initiating concomitant drugs. Continue monitoring and increase digoxin dose by approximately 20-40% as necessary.

Potentially Significant Pharmacodynamic Drug Interactions

Because of considerable variability of pharmacodynamic interactions, the dosage of digoxin should be individualized when patients receive these medications concurrently.

Drugs that Affect Renal Function

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.

Antiarrthymics

Dofetilide

Concomitant administration with digoxin was associated with a higher rate of torsades de pointes

Sotalol

Proarrhythmic events were more common in patients receiving sotalol and digoxin than on either alone; it is not clear whether this represents an interaction or is related to the presence of CHF, a known risk factor for proarrhythmia, in patients receiving digoxin.

Dronedarone

Sudden death was more common in patients receiving digoxin with dronedarone than on either alone; it is not clear whether this represents an interaction or is related to the presence of advanced heart disease, a known risk factor for sudden death in patients receiving digoxin.

Parathyroid Hormone Analog

Teriparatide

Sporadic case reports have suggested that hypercalcemia may predispose patients to digitalis toxicity. Teriparatide transiently increases serum calcium.

Thyroid supplement

Thyroid

Treatment of hypothyroidism in patients taking digoxin may increase the dose requirements of digoxin.

Sympathomimetics

Epinephrine
Norepinephrine     
Dopamine

Can increase the risk of cardiac arrhythmias

Neuromuscular Blocking Agents     

Succinylcholine

May cause sudden extrusion of potassium from muscle cells causing arrhythmias in patients taking digoxin.

Supplements

Calcium

If administered rapidly by intravenous route, can produce serious arrhythmias in digitalized patients.

Beta-adrenergic blockers and calcium channel blockers

Additive effects on AV node conduction can result in bradycardia and advanced or complete heart block.

Hyperpolarization-activated cyclic nucleotide-gated channel blocker

Ivabradine

Can increase the risk of bradycardia

Drug/Laboratory Test Interactions

Endogenous substances of unknown composition (digoxin-like immunoreactive substances, [DLIS]) can interfere with standard radioimmunoassays for digoxin. The interference most often causes results to be falsely positive or falsely elevated, but sometimes it causes results to be falsely reduced. Some assays are more subject to these failings than others. Several LC/MS/MS methods are available that may provide less susceptibility to DLIS interference. DLIS are present in up to half of all neonates and in varying percentages of pregnant women, patients with hypertrophic cardiomyopathy, patients with renal or hepatic dysfunction, and other patients who are volume-expanded for any reason. The measured levels of DLIS (as digoxin equivalents) are usually low (0.2-0.4 ng/mL), but sometimes they reach levels that would be considered therapeutic or even toxic.

In some assays, spironolactone, canrenone, and potassium canrenoate may be falsely detected as digoxin, at levels up to 0.5 ng/mL. Some traditional Chinese and Ayurvedic medicine substances like Chan Su, Siberian Ginseng, Asian Ginseng, Ashwagandha or Dashen, can cause similar interference.

Spironolactone and DLIS are much more extensively protein-bound than digoxin. As a result, assays of free digoxin levels in protein-free ultrafiltrate (which tend to be about 25% less than total levels, consistent with the usual extent of protein binding) are less affected by spironolactone or DLIS. It should be noted that ultrafiltration does not solve all interference problems with alternative medicines. The use of an LC/MS/MS method may be the better option according to the good results it provides, especially in terms of specificity and limit of quantization.

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