"The U.S. Food and Drug Administration today approved Entresto (sacubitril/valsartan) tablets for the treatment of heart failure. The drug has been shown to reduce the rate of cardiovascular death and hospitalization related to heart failure."...
The following adverse reactions are included in more detail in the WARNINGS AND PRECAUTIONS section of the label:
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].
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.
Read the Lanoxin Injection (digoxin injection) Side Effects Center for a complete guide to possible side effects
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. Drugs that induce or inhibit P-glycoprotein in intestine or kidney have the potential to alter digoxin pharmacokinetics.
Pharmacokinetic Drug Interactions
Pharmacokinetic interactions have been observed and reported primarily when digoxin is coadministered by oral route. There are very few studies that have evaluated the drug interaction when digoxin is administered via IV route. The magnitude of digoxin exposure change through IV route is generally lower than that through oral route. Table below provides available interaction data using digoxin IV formulation (NA means not available).
|Digoxin concentrations increased greater than 50%|
|Digoxin Serum Concentration Increase||Digoxin AUC Increase||Recommendations|
|Quinidine||NA||54-83%||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.|
|Digoxin concentrations increased less than 50%|
|Amiodarone||17%||40%||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.|
|No significant Digoxin exposure changes|
|Please refer to section 12 for a complete list of drugs that were studied but reported no significant changes on digoxin exposure.||No additional actions are required.|
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.|
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.
Read the Lanoxin Injection Drug Interactions Center for a complete guide to possible interactions
Last reviewed on RxList: 6/17/2013
This monograph has been modified to include the generic and brand name in many instances.
Additional Lanoxin Injection Information
- Lanoxin Injection Drug Interactions Center: digoxin inj
- Lanoxin Injection Side Effects Center
- Lanoxin Injection FDA Approved Prescribing Information including Dosage
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
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