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hepatotoxicity associated

with dronedarone use. As part of this warning, two cases of

501Cardiac Arrhythmias Chapter 20

hepatic failure requiring transplantation and several less severe

cases of hepatotoxicity were described (for more information, see

http://www.fda.gov/Drugs/DrugSafety/ucm240011.htm).

In view of J.K.’s new onset of HF, sotalol, propafenone, and

flecainide would not be indicated. Although dronedarone may

be better tolerated than amiodarone, it would be contraindicated because J.K. was recently admitted with decompensated

HF. Therefore, the only available options for J.K. would be either

dofetilide or amiodarone, both of which have been proven safe in

patients with HF. Selection between dofetilide and amiodarone

could be based on renal function, the presence of any major drug

interactions, or the desire to avoid adverse effects with amiodarone.

CASE 20-1, QUESTION 12: J.K. is to begin dofetilide today.

As a precaution, he is admitted for dofetilide initiation. Why

would J.K. need to be admitted for dofetilide initiation? Is

it necessary to initiate all antiarrhythmic medications in the

hospital?

Dofetilide was approved with the requirement for in-hospital

initiation because of the relatively high risk of TdP. ECG monitoring is required for patients being initiated on dofetilide for

a minimum of 3 days in a properly equipped facility. The initial regimen is determined by the patient’s estimated creatinine

clearance. The QTc interval must be measured (using a 12-lead

ECG) 2 to 3 hours after the first dose and each subsequent dose

while the patient is hospitalized. If the QTc interval increases by

greater than 15% or if it surpasses 500 ms (550 ms in patients

with ventricular conduction abnormalities) after the first dose,

the dofetilide regimen should be reduced by 50%. If the QTc

interval exceeds the above parameters any time after the second

subsequent dose, dofetilide should be discontinued.80

Sotalol may also be arrhythmogenic in high doses, and the

risk of inducing TdP has prompted its manufacturer to mandate

a minimum of 3 days of ECG monitoring in a properly equipped

facility during therapy initiation as well.85 Further, during initiation and titration, QTc intervals should be monitored 2 to 4

hours after each dose. In fact, most antiarrhythmic agents for

AF should probably be initiated in the inpatient setting, with the

exception of amiodarone owing to the low risk of proarrhythmia

with this drug.11

STROKE PREVENTION

ANTITHROMBOTIC THERAPY

CASE 20-1, QUESTION 13: J.K. is discharged from the hospital on dofetilide 500 mcg twice daily, which is appropriate given his CrCl of 92 mL/minute. He has been doing fine

for 2 weeks after discharge. Should J.K. remain on warfarin

therapy? Could any other antithrombotic options be considered?