What drugs interact with digoxin and amiodarone?

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.