Digoxin (Page 5 of 8)

7.3 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 EpinephrineNorepinephrine 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.

7.4 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 to 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.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Category C.

Digoxin Tablets should be given to a pregnant woman only if clearly needed. It is also not known whether digoxin can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Animal reproduction studies have not been conducted with digoxin.

8.2 Labor and Delivery

There are not enough data from clinical trials to determine the safety and efficacy of digoxin during labor and delivery.

8.3 Nursing Mothers

Studies have shown that digoxin distributes into breast milk and that the milk-to-serum concentration ratio is approximately 0.6 to 0.9. However, the estimated exposure of a nursing infant to digoxin via breastfeeding is far below the usual infant maintenance dose. Therefore, this amount should have no pharmacologic effect upon the infant.

8.4 Pediatric Use

The safety and effectiveness of Digoxin Tablets in the control of ventricular rate in children with atrial fibrillation have not been established.

The safety and effectiveness of Digoxin Tablets in the treatment of heart failure in children have not been established in adequate and well-controlled studies. However, in published literature of children with heart failure of various etiologies (e.g., ventricular septal defects, anthracycline toxicity, patent ductus arteriosus), treatment with digoxin has been associated with improvements in hemodynamic parameters and in clinical signs and symptoms.

Newborn infants display considerable variability in their tolerance to digoxin. Premature and immature infants are particularly sensitive to the effects of digoxin, and the dosage of the drug must not only be reduced but must be individualized according to their degree of maturity.

8.5 Geriatric Use

The majority of clinical experience gained with digoxin has been in the elderly population. This experience has not identified differences in response or adverse effects between the elderly and younger patients. However, this drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, which should be based on renal function, and it may be useful to monitor renal function [see Dosage and Administration (2.1)].

8.6 Renal Impairment

The clearance of digoxin can be primarily correlated with the renal function as indicated by creatinine clearance. Tables 3 and 5 provide the usual daily maintenance dose requirements for digoxin based on creatinine clearance [see Dosage and Administration (2.3)].

Digoxin is primarily excreted by the kidneys; therefore, patients with impaired renal function require smaller than usual maintenance doses of digoxin [see Dosage and Administration (2.3)]. Because of the prolonged elimination half-life, a longer period of time is required to achieve an initial or new steady-state serum concentration in patients with renal impairment than in patients with normal renal function. If appropriate care is not taken to reduce the dose of digoxin, such patients are at high risk for toxicity, and toxic effects will last longer in such patients than in patients with normal renal function.

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