Pharmacokinetic drug interactions with amiodarone.
Amiodarone alters the pharmacokinetics, and in some cases the pharmacodynamics, of several clinically important drugs. The major mechanisms of its drug interactions is inhibition of hepatic metabolism, but it can also affect the bioavailability, protein binding and renal excretion of coadministered drugs. It significantly increases the plasma concentrations of digoxin, warfarin, many Class I antiarrhythmic drugs (quinidine, procainamide, aprindine and flecainide) and phenytoin, in some instances resulting in overt signs of clinical toxicity, including adverse cardiovascular, cardiac and central nervous system effects. In most cases 20 to 50% reductions in doses of the affected drugs are necessary to offset the pharmacokinetic alterations and increased plasma drug concentrations caused by amiodarone. Interactions between amiodarone and beta-blockers (e.g. propranolol) and calcium channel blockers (e.g. diltiazem) are associated more with electrophysiological (sinus bradycardia and sinus arrest) and/or haemodynamic toxicity, due to additive pharmacological effects, than to changes in pharmacokinetics. In patients undergoing surgical procedures amiodarone interacts with general and local anaesthetic agents, resulting in an increased risk of cardiac system complications including hypotension and bradycardia. There is still a need for prospective controlled clinical studies to be conducted on many likely combinations of other drugs with amiodarone to increase understanding of the magnitude, time-course, mechanism and relevance of pharmacokinetic changes caused by this drug.