LANOXIN (Page 4 of 9)

6 ADVERSE REACTIONS

The following adverse reactions are included in more detail in the Warnings and Precautions section of the label:

  • Cardiac arrhythmias [see Warnings and Precautions (5.1, 5.2)]
  • Digoxin Toxicity [see Warnings and Precautions (5.3)]

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

In general, the adverse reactions of LANOXIN are dose-dependent and occur at doses higher than those needed to achieve a therapeutic effect. Hence, adverse reactions are less common when LANOXIN is used within the recommended dose range, is maintained within the therapeutic serum concentration range, and when there is careful attention to concurrent medications and conditions.

In the DIG trial (a trial investigating the effect of digoxin on mortality and morbidity in patients with heart failure), the incidence of hospitalization for suspected digoxin toxicity was 2% in patients taking LANOXIN compared to 0.9% in patients taking placebo [see Clinical Studies (14.1)].

The overall incidence of adverse reactions with digoxin has been reported as 5-20%, with 15-20% of adverse events considered serious. Cardiac toxicity accounts for about one-half, gastrointestinal disturbances for about one-fourth, and CNS and other toxicity for about one-fourth of these adverse events.

Gastrointestinal: In addition to nausea and vomiting, the use of digoxin has been associated with abdominal pain, intestinal ischemia, and hemorrhagic necrosis of the intestines.

CNS: Digoxin can cause headache, weakness, dizziness, apathy, confusion, and mental disturbances (such as anxiety, depression, delirium, and hallucination).

Other: Gynecomastia has been occasionally observed following the prolonged use of digoxin. Thrombocytopenia and maculopapular rash and other skin reactions have been rarely observed.

7 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.

7.1 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.

7.2 Pharmacokinetic Drug Interactions

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
Mirabegron 29% 27%
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, sulfasalazine Measure serum digoxin concentrations before initiating concomitant drugs. Continue monitoring and increase digoxin dose by approximately 20-40% as necessary.

NA – Not available/reported

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