Digoxin - Adverse Effects

Adverse Effects

The occurrence of adverse drug reactions is common, owing to its narrow therapeutic index (the margin between effectiveness and toxicity). Adverse effects are concentration-dependent, and are rare when plasma digoxin concentration is <0.8 μg/l. They are also more common in patients with low potassium levels (hypokalemia), since digoxin normally competes with K+ ions for the same binding site on the Na+/K+ ATPase pump.

Common adverse effects (≥1% of patients) include: loss of appetite, nausea, vomiting and diarrhea as gastrointestinal motility increases. Other common effects are blurred vision, visual disturbances (yellow-green halos and problems with color perception), confusion, drowsiness, dizziness, insomnia, nightmares, agitation, and depression, as well as a higher acute sense of sensual activities. Less frequent adverse effects (0.1%–1%) include: acute psychosis, delirium, amnesia, convulsions, shortened QRS complex, atrial or ventricular extrasystoles, paroxysmal atrial tachycardia with AV block, ventricular tachycardia or fibrillation, and heart block. Rarely, digoxin has been shown to cause thrombocytopenia. Gynaecomastia (enlargement of breast tissue) is mentioned in many textbooks as a side effect, thought to be due to the estrogen-like steroid moiety of the digoxin molecule, but when systematically sought, the evidence for this is equivocal. The pharmacological actions of digoxin usually result in electrocardiogram changes, including ST depression or T wave inversion, which do not indicate toxicity. PR interval prolongation, however, may be a sign of digoxin toxicity. Additionally, increased intracellular Ca2+ may cause a type of arrhythmia called bigeminy (coupled beats), eventually ventricular tachycardia or fibrillation. The combination of increased (atrial) arrhythmogenesis and inhibited atrioventricular conduction (for example paroxysmal atrial tachycardia with A-V block - so-called "PAT with block") is said to be pathognomonic (i.e. diagnostic) of digoxin toxicity.

An often described, but rarely seen, adverse effect of digoxin is a disturbance of color vision (mostly yellow and green) called xanthopsia. Vincent van Gogh's "Yellow Period" may have somehow been influenced by concurrent digitalis therapy. Other oculotoxic effects of digoxin include generalized blurry vision, as well as seeing a "halo" around each point of light. The latter effect can also be seen in van Gogh's Starry Night. Evidence of van Gogh's digoxin use is supported by multiple self portraits that include the foxglove plant, from which digoxin is obtained. (e.g. Portrait of Dr. Gachet)

Digoxin plasma concentrations may increase while on antimalarial medication hydroxychloroquine (based on two case reports from 1982).

In overdose, the usual supportive measures are needed. If arrhythmias prove troublesome, or malignant hyperkalaemia occurs (inexorably rising potassium level due to paralysis of the cell membrane-bound, ATPase-dependent Na/K pumps), the specific antidote is antidigoxin (antibody fragments against digoxin, trade names Digibind and Digifab). Toxicity can also be treated with higher than normal doses of potassium. Digoxin is not removed by hemodialysis or peritoneal dialysis with enough effectiveness to treat toxicity.

Digoxin has potentially dangerous interactions with verapamil, amiodarone, erythromycin, and epinephrine (as would be injected with a local anesthetic).