Digoxin vs. amiodarone

• Digoxin and amiodarone are heart medications used to treat abnormal heart rhythms and congestive heart failure.
• Digoxin also is used for increasing myocardial contractility in pediatric patients with heart failure.
• Brand names for digoxin include Lanoxin and Lanoxin Pediatric.
• Brand names for amiodarone include Cordarone, Nextrone, and Pacerone.
• Digoxin and amiodarone belong to different drug classes. Digoxin is a cardiac glycoside and amiodarone is an antiarrhythmic medication.
• Side effects of digoxin and amiodarone that are similar include nausea, vomiting, and dizziness.
• Side effects of digoxin that are different from amiodarone include diarrhea, headache, skin rash, and mental changes.
• Side effects of amiodarone that are different from digoxin include fatigue, eye deposits, tremor, unsteady gait, constipation, weight loss, and visual changes.

Digoxin is a cardiac glycoside used for treating adults with mild to moderate congestive heart failure and for treating abnormally rapid atrial rhythms (such as atrial fibrillation, atrial flutter, and atrial tachycardia). Digoxin also is used for increasing heart contractions in pediatric patients with heart failure. Digoxin increases the force of contraction of the heart muscle by inhibiting the activity of the enzyme ATPase that controls movement of sodium, potassium, and calcium into the heart muscle. Calcium controls the force of contraction, so inhibiting ATPase increases calcium in the heart muscle that results in increases in the force of heart contractions. Digoxin also slows electrical conduction between the atria and the ventricles of the heart, which is why it is used to treat abnormally rapid atrial rhythms.

Amiodarone is an antiarrhythmic medication. Amiodarone is considered a "broad spectrum" antiarrhythmic medication, that is, it has multiple and complex effects on the electrical activity of the heart, which is responsible for the heart's rhythm. Among its most important electrical effects are a delay in the rate at which the heart's electrical system "recharges" after the heart contracts (repolarization); a prolongation in the electrical phase during which the heart's muscle cells are electrically stimulated (action potential); a slowing of the speed of electrical conduction (how fast each individual impulse is conducted through the heart's electrical system); a reduction in the rapidity of firing of the normal generator of electrical impulses in the heart (the heart's pacemaker); and a slowing of conduction through various specialized electrical pathways (called accessory pathways), which can be responsible for arrhythmias. Amiodarone also causes blood vessels to dilate, which can result in a drop in blood pressure. Because of this effect, it also may be of benefit in patients with congestive heart failure.

Digoxin

Common side effects include:

• nausea,
• diarrhea,
• vomiting,
• headache,
• dizziness,
• skin rash, and
• mental changes.

Many digoxin side effects are dose dependent and happen when blood levels are over the narrow therapeutic range. Therefore, digoxin side effects can be avoided by keeping blood levels within the therapeutic level.

Serious side effects associated with digoxin include:

• heart block,
• rapid heartbeat, and
• slow heart rate.

Digoxin has also been associated with visual disturbance (blurred or yellow vision), abdominal pain, and breast enlargement. Patients with low blood potassium levels can develop digoxin toxicity even when digoxin levels are not considered elevated. Similarly, high calcium and low magnesium blood levels can increase digoxin toxicity and produce serious disturbances in heart rhythm.

Amiodarone

WARNING

Amiodarone is intended for use only in patients with the indicated life-threatening arrhythmias because its use is accompanied by substantial toxicity.

Amiodarone has several potentially fatal toxicities, the most important of which is pulmonary toxicity (hypersensitivity pneumonitis or interstitial/alveolar pneumonitis) that has resulted in clinically manifest disease at rates as high as 10% to 17% in some series of patients with ventricular arrhythmias given doses of around 400 mg/day, and as abnormal diffusion capacity without symptoms in a much higher percentage of patients. Pulmonary toxicity has been fatal about 10% of the time.

Liver injury is common with amiodarone, but is usually mild and evidenced only by abnormal liver enzymes. Overt liver disease can occur, however, and has been fatal in a few cases.

Like other antiarrhythmics, amiodarone can exacerbate the arrhythmia, for example, by making the arrhythmia less well tolerated or more difficult to reverse. This has occurred in 2% to 5% of patients in various series, and significant heart block or sinus bradycardia has been seen in 2% to 5%. All of these events should be manageable in the proper clinical setting in most cases. Although the frequency of such proarrhythmic events does not appear greater with amiodarone than with many other agents used in this population, the effects are prolonged when they occur.

Even in patients at high risk of arrhythmic death, in whom the toxicity of amiodarone is an acceptable risk, amiodarone poses major management problems that could be life threatening in a population at risk of sudden death, so that doctors should make every effort to utilize alternative agents first.

The difficulty of using amiodarone effectively and safely itself poses a significant risk to patients. Patients with the indicated arrhythmias must be hospitalized while the loading dose of amiodarone is given, and a response generally requires at least one week, usually two or more. Because absorption and elimination are variable, maintenance-dose selection is difficult, and it is not unusual to require dosage decrease or discontinuation of treatment.

Common side effects

Common side effects include:

• fatigue,
• eye deposits,
• tremor,
• unsteady gait,
• nausea,
• vomiting,
• constipation,
• weight loss,
• dizziness, and
• visual changes.

Amiodarone is also associated with:

• heart block,
• low blood pressure,
• pulmonary fibrosis (scarring of the lungs),
• heart failure,
• cardiac arrest,
• hypothyroidism or hyperthyroidism,
• blue skin discoloration,
• liver failure, and
• cardiogenic shock.

Digoxin

• Digoxin may be taken with or without food.
• Digoxin primarily is eliminated by the kidneys; therefore, the dose of digoxin should be reduced in patients with kidney dysfunction.
• Digoxin blood levels are used for adjusting doses in order to avoid toxicity.
• The usual starting dose is 0.0625-0.25 mg daily depending on age and kidney function.
• The dose may be increased every two weeks to achieve the desired response.
• The usual maintenance dose is 0.125 to 0.5 mg per day.

Amiodarone

The recommended dosing schedule is an initial loading dose of 800-1600 mg daily for 1 to 3 weeks, followed by 600-800 mg daily for 1 month, then 400 mg daily for maintenance. Doctors should closely monitor response and individualize dosage for each patient. Amiodarone may be administered once daily or given twice daily with meals to minimize stomach upset, which is seen more frequently with higher doses.

Digoxin

Drugs such as gentamicin, tetracycline, ranolazine (Ranexa), verapamil (Calan, Verelan, Verelan PM, Isoptin, Isoptin SR, Covera-HS), quinidine (Quinaglute, Quinide), amiodarone (Cordarone), indomethacin (Indocin, Indocin-SR), alprazolam (Xanax, Xanax XR, Niravam), spironolactone (Aldactone), and itraconazole (Sporanox) can increase digoxin levels and the risk of toxicity. The co-administration of digoxin and beta-blockers (for example propranolol [Inderal, Inderal LA]) or calcium channel blockers or CCBs (for example, verapamil), which also reduce heart rate, can cause serious heart rate slowing.

Diuretic-induced (for example, by furosemide [Lasix]) reduction in blood potassium or magnesium levels may predispose patients to digoxin-induced abnormal heart rhythms.

Saquinavir (Invirase) and ritonavir (Norvir) increase the amount of digoxin in the body and may cause digoxin toxicity.

Mirabegron (Mybetriq) increases digoxin blood levels. The lowest dose of digoxin should be used if by people who are also using mirabegron.

Omeprazole (Prilosec) and other drugs that reduce stomach acidity may increase blood levels of digoxin.

Amiodarone

Amiodarone may interact with beta-blockers such as atenolol (Tenormin), propranolol (Inderal), metoprolol (Lopressor), or certain calcium channel blockers, such as verapamil (Calan, Isoptin, Verelan, Covera-HS) or diltiazem (Cardizem, Dilacor, Tiazac), resulting in an excessively slow heart rate or a block in the conduction of the electrical impulse through the heart.

Amiodarone increases the blood levels of digoxin (Lanoxin) when the two drugs are given together. It is recommended that the dose of digoxin be cut by 50% when amiodarone therapy is started. Flecainide (Tambocor) blood concentrations increase by more than 50% with amiodarone. Procainamide (Procan-SR, Pronestyl) and quinidine (Quinidex, Quinaglute) concentrations increase by 30%-50% during the first week of amiodarone therapy. Additive electrical effects occur with these combinations, and worsening arrhythmias may occur as a result. Some experts recommend that the doses of these other drugs be reduced when amiodarone is started. Amiodarone can result in phenytoin (Dilantin) toxicity because it causes a two- or three-fold increase in blood concentrations of phenytoin. Symptoms of phenytoin toxicity including unsteady eye movement (temporary and reversible), tiredness, and unsteady gait.

Ritonavir (Norvir), tipranavir (Aptivus), indinavir (Crixivan), and saquinavir (Invirase) can inhibit the enzyme that is responsible for the metabolism (break-down) of amiodarone. They should not be combined with amiodarone.

Amiodarone also can interact with tricyclic antidepressants (for example, amitriptyline [Endep, Elavil]), or phenothiazines (for example, chlorpromazine [Thorazine]) and potentially cause serious arrhythmias.

Amiodarone interacts with warfarin (Coumadin) and increases the risk of bleeding. The bleeding can be serious or even fatal. This effect can occur as early as 4-6 days after the start of the combination of drugs or can be delayed by a few weeks. Clotting studies probably should be done early during treatment with amiodarone among patients taking warfarin.

Amiodarone can interact with some cholesterol-lowering medicines of the statin class, such as simvastatin (Zocor), atorvastatin (Lipitor), and lovastatin (Mevacor), increasing the side effects of statins, which include severe muscle breakdown, kidney failure, or liver disease. This interaction is dose-related, meaning that lower doses of statins are safer than higher doses when used with amiodarone. An alternative statin, pravastatin (Pravachol), does not share this interaction and is safer in patients taking amiodarone.

Amiodarone inhibits the metabolism of dextromethorphan, the cough suppressant found in most over-the-counter (and some prescription) cough and cold medications (for example, Robitussin-DM). Although the significance of the interaction is unknown, these two drugs probably should not be taken together if possible.

Grapefruit juice may reduce the breakdown of amiodarone in the stomach, leading to increased amiodarone blood levels. Grapefruit juice should be avoided during treatment with amiodarone.

Digoxin

There are no adequate studies in pregnant women.

Digoxin is secreted in breast milk at concentrations similar to concentrations in the mother's blood. However, the total amount of digoxin that will be absorbed from breast milk by the infant may not be enough to cause effects. Nursing mothers who are taking digoxin should exercise caution.

Amiodarone

Amiodarone should not be used during pregnancy because it can cause fetal harm. There have been reports of congenital hypothyroidism or hyperthyroidism when amiodarone was administered during pregnancy.

Amiodarone is excreted in breast milk and may cause adverse effects in the infant. Mothers receiving amiodarone should discontinue breastfeeding.