Evaluation of the Dofetilide Risk-Management Program
Background: Dose-dependent torsades de pointes has been shown to occur with dofetilide (Tikosyn) and sotalol HCl (Betapace AF); thus, detailed dosing and monitoring recommendations to minimize this risk are included in the product labeling for both drugs. Only dofetilide, however, has a mandated risk-management program that restricts distribution of the drug and requires prescriber education on the drug. We investigated whether this program improved adherence to dosing and monitoring recommendations for dofetilide as compared with sotalol.
Methods: Charts for 47 patients taking dofetilide and 117 patients taking sotalol were reviewed.
Results: The recommended starting dose was prescribed more frequently in the dofetilide group than in the sotalol group (79% vs 35%, P <.001). A higher number of patients in the dofetilide group compared with the sotalol group received the recommended baseline tests for potassium (100% vs 82%, P <.001), magnesium (89% vs 38%, P <.001), serum creatinine (100% vs 82%, P <.001), and electrocardiography (94% vs 67%, P <.001). A significantly greater proportion of patients in the dofetilide group received recommended electrocardiograms obtained after the first dose (94% for dofetilide vs 43% for sotalol, P <.001) and subsequent doses (80% for dofetilide vs 3.5% for sotalol, P <.001).
Conclusion: Better adherence to several dosing and monitoring recommendations in the dofetilide group may be caused by the presence of the risk-management program. However, low usage of dofetilide during the study period may signify an unintended, negative consequence of the risk-management program.
Dofetilide (Tikosyn) is a new oral anti-arrhythmic medication that has been approved for the conversion of atrial fibrillation and atrial flutter and the maintenance of sinus rhythm in patients with atrial fibrillation and atrial flutter. Similar to sotalol, dofetilide is associated with a dose- and concentration-dependent incidence of QT-prolongation and torsades de pointes. As a condition for approval of dofetilide in the United States, the Food and Drug Administration (FDA) required that a distribution and education program be developed to minimize the risk of this potentially life-threatening proarrhythmia. In response, Pfizer developed a risk-management program that stipulated: a restriction of dofetilide initiation to hospitalized patients; restrictions in outpatient dispensing; a requirement that prescribing physicians complete an educational program on dofetilide; and the establishment of detailed dosing and monitoring recommendations for the drug.
Shortly after dofetilide was approved for use in the United States, the FDA also approved Betapace AF (sotalol HCl), a new sotalol product indicated to maintain sinus rhythm in patients with a history of atrial fibrillation and atrial flutter. The FDA did not request a risk-management program for sotalol because this drug had already been marketed in the United States for the treatment of ventricular arrhythmias. However, the product labeling for Betapace AF contained detailed dosing and monitoring recommendations similar to the language in the product labeling for dofetilide.
Because the labeled dosing and monitoring recommendations for both medications were developed to minimize the risk of torsades de pointes, adherence to the recommendations would be expected to reduce risk. The purpose of this study was to determine whether a mandated risk-management program for dofetilide was effective in improving compliance with labeled dosing and monitoring recommendations. This was accomplished by comparing the adherence of dofetilide prescribers to these labeling recommendations to the adherence of sotalol prescribers to similar labeling recommendations.
Background: Dose-dependent torsades de pointes has been shown to occur with dofetilide (Tikosyn) and sotalol HCl (Betapace AF); thus, detailed dosing and monitoring recommendations to minimize this risk are included in the product labeling for both drugs. Only dofetilide, however, has a mandated risk-management program that restricts distribution of the drug and requires prescriber education on the drug. We investigated whether this program improved adherence to dosing and monitoring recommendations for dofetilide as compared with sotalol.
Methods: Charts for 47 patients taking dofetilide and 117 patients taking sotalol were reviewed.
Results: The recommended starting dose was prescribed more frequently in the dofetilide group than in the sotalol group (79% vs 35%, P <.001). A higher number of patients in the dofetilide group compared with the sotalol group received the recommended baseline tests for potassium (100% vs 82%, P <.001), magnesium (89% vs 38%, P <.001), serum creatinine (100% vs 82%, P <.001), and electrocardiography (94% vs 67%, P <.001). A significantly greater proportion of patients in the dofetilide group received recommended electrocardiograms obtained after the first dose (94% for dofetilide vs 43% for sotalol, P <.001) and subsequent doses (80% for dofetilide vs 3.5% for sotalol, P <.001).
Conclusion: Better adherence to several dosing and monitoring recommendations in the dofetilide group may be caused by the presence of the risk-management program. However, low usage of dofetilide during the study period may signify an unintended, negative consequence of the risk-management program.
Dofetilide (Tikosyn) is a new oral anti-arrhythmic medication that has been approved for the conversion of atrial fibrillation and atrial flutter and the maintenance of sinus rhythm in patients with atrial fibrillation and atrial flutter. Similar to sotalol, dofetilide is associated with a dose- and concentration-dependent incidence of QT-prolongation and torsades de pointes. As a condition for approval of dofetilide in the United States, the Food and Drug Administration (FDA) required that a distribution and education program be developed to minimize the risk of this potentially life-threatening proarrhythmia. In response, Pfizer developed a risk-management program that stipulated: a restriction of dofetilide initiation to hospitalized patients; restrictions in outpatient dispensing; a requirement that prescribing physicians complete an educational program on dofetilide; and the establishment of detailed dosing and monitoring recommendations for the drug.
Shortly after dofetilide was approved for use in the United States, the FDA also approved Betapace AF (sotalol HCl), a new sotalol product indicated to maintain sinus rhythm in patients with a history of atrial fibrillation and atrial flutter. The FDA did not request a risk-management program for sotalol because this drug had already been marketed in the United States for the treatment of ventricular arrhythmias. However, the product labeling for Betapace AF contained detailed dosing and monitoring recommendations similar to the language in the product labeling for dofetilide.
Because the labeled dosing and monitoring recommendations for both medications were developed to minimize the risk of torsades de pointes, adherence to the recommendations would be expected to reduce risk. The purpose of this study was to determine whether a mandated risk-management program for dofetilide was effective in improving compliance with labeled dosing and monitoring recommendations. This was accomplished by comparing the adherence of dofetilide prescribers to these labeling recommendations to the adherence of sotalol prescribers to similar labeling recommendations.
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