Handbook of Drug Interactions

226 Auer
low cardiac output. Important interactions with other drugs occur, and when given
concomitantly with amiodarone, the dose of warfarin, digoxin, and other antiarrhythmic
drugs should be reduced by one-third to one-half and the patient watched closely. Drugs
with synergistic actions, such as beta-blockers or calcium channel blockers, must be
given cautiously.
1.2.11. Bretylium (Class III)
This drug, which is used for refractory ventricular tachyarrhythmias, may present
particular problems in patients with renal dysfunction because its kinetics appear complex
and have not been defined for this group of patients. Therapy with this drug in
patients with renal disease should be extremely conservative.
1.2.12. Sotalol (Class III)
Proarrhythmia is the most serious adverse effect (8). Overall, new or worsened
ventricular tachyarrhythmias occur in about 4%, and this response is due to torsades
de pointes in about 2.5%. The incidence of torsades de pointes increases to 4% in
patients with a history of sustained ventricular tachycardia and is dose related, reportedly
only 1.6% at 320 mg/d but 4.4% at 480 mg/d. Other adverse effects commonly
seen with other beta-blockers also apply to sotalol. Sotalol should be used with caution
or not at all in combination with other drugs that prolong the QT interval. However,
such combinations have been used successfully.
1.2.13. Adenosine
Transient side effects occur in almost 40% of patients with supraventricular tachycardia
given adenosine and are most commonly flushing, dyspnea, and chest pressure.
These symptoms are fleeting, generally less than 1 min, and are well tolerated. Premature
ventricular complexes, transient sinus bradycardia, sinus arrest, and AV block are
common when a supraventricular tachycardia abruptly terminates. Induction of atrial
fibrillation can be problematic in patients with the Wolff-Parkinson-White syndrome
or rapid AV conduction.
1.3. Drug Interactions (Selection; Amiodarone Preferred)
Drug interactions associated with amiodarone are pharmacodynamic and/or pharmacokinetic
in nature. The pharmacodynamic interactions associated with amiodarone
occur primarily with other antiarrhythmics and are a consequence of additive or synergistic
electrophysiologic effects. As the pharmacologic effects of amiodarone are delayed
by several days even with adequate loading doses, concomitant use of another antiarrhythmic
is often necessary. Should this be the case, the dose of the secondary antiarrhythmic
should, in general, be decreased by 30–50% after the first few days of initiating
amiodarone therapy. Discontinuation of the second antiarrhythmic agent should be
attempted as soon as the therapeutic effects of amiodarone are observed. Conversely,
in patients requiring combination therapy, the dose of the second antiarrhythmic should,
in general, be decreased by 50% until amiodarone eliminated from the body. Proarrhythmia,
including torsade de pointes (Table 1) and monomorphic ventricular tachycardia
can and has occurred when amiodarone was administered in combination with any num-