Dofetilide Risk-Management Program
Study Objective: To assess the opinions and knowledge retention of practitioners after participation in the dofetilide risk-management program.
Design: A 21-item questionnaire.
Setting: A large academic medical center.
Participants: One hundred forty-six practitioners were given the questionnaire; 91 (62%) completed it.
Measurements and Results: The questionnaire assessed practitioners' opinions of the program and guidelines, preparation time for implementing dofetilide treatment, and retention of facts from the program. Responses were graded on a 5-point Likert scale. Practitioners took a mean of 0.86 ± 0.44 hours to complete the program; physicians took the least time, pharmacists the most. Practitioners agreed the program was necessary but were undecided about whether the guidelines were easily understood or implemented. Nurses answered one of the two knowledge-retention questions incorrectly significantly more often than physicians or pharmacists. Identification of seven drugs that should not be taken with dofetilide differed significantly (p<0.0001) across groups (mean accuracy score was 41% for nurses, 80% for pharmacists, and 86% for physicians).
Conclusion: This risk-management program has been well received by practitioners at our institution. We are gathering data to determine whether the program is effective in reducing inappropriate administration of dofetilide.

In October 1999, a new Vaughan Williams class III antiarrhythmic agent, dofetilide, was approved for treatment of atrial fibrillation or flutter in the United States. This was the first new oral antiarrhythmic agent approved for treatment of atrial arrhythmias in almost a decade. It also was the first antiarrhythmic agent for which studies of overall mortality risk were conducted before market approval was requested. These studies showed no increased risk of death in patients taking dofetilide who had heart failure or previous myocardial infarction.

Dofetilide, however, causes a dose- and concentration-dependent increase in the QT interval that can lead to torsades de pointes. During clinical trials, the prevalence of this potentially fatal adverse effect was reduced dramatically when lower dosages were administered and when dosage was decreased for patients with impaired renal function. Several other oral antiarrhythmic drugs on the market also can cause torsades de pointes. Two of these, sotalol and quinidine, like dofetilide, are approved for treatment of atrial arrhythmias. However, unlike the requirements for any other antiarrhythmic agent approved for marketing in the United States, the Food and Drug Administration (FDA) mandated a risk-management program when it approved dofetilide. This program requires all practitioners to complete an education program before they prescribe dofetilide. The program ensures that prescribers receive important information about appropriate dosing and monitoring of dofetilide before administering it.

Several drugs have been removed from the market because of errors related to inappropriate dosing or drug interactions that precipitated torsades de pointes. None of these drugs were antiarrhythmic agents, but the FDA had found that postmarketing labeling changes and warning letters to health care practitioners were ineffective in changing prescribing patterns and reducing the risk of torsades de pointes. The dofetilide risk-management program was an attempt to disseminate important dosing and monitoring guidelines to practitioners before allowing them to prescribe, dispense, or administer dofetilide.

Because of the novelty of this program and the uncertainty of its acceptance by prescribers, the Duke Center for Education and Research on Therapeutics (CERTs) evaluated the opinions and knowledge of practitioners at Duke University Medical Center (DUMC) after they participated in the dofetilide risk-management program.