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).


CONCLUSIONS
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.
Duke Center for Education and Research on Therapeutics and the Division of Cardiology, Duke Clinical Research Institute, Durham, NC 27715, USA. allen003@mc.duke.edu
Nancy M
NM
Allen LaPointe
Anita
A
Chen
Bradley
B
Hammill
Elizabeth
E
DeLong
Judith M
JM
Kramer
Robert M
RM
Califf
D001145:Arrhythmias, Cardiac / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D016903:Drug Monitoring / Q000379:methods; D004562:Electrocardiography; D005260:Female; D019983:Guideline Adherence / Q000706:statistics & numerical data*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009657:North Carolina; D010627:Phenethylamines / Q000008:administration & dosage / Q000009:adverse effects*; D017410:Practice Guidelines as Topic; D011356:Product Labeling; D015397:Program Evaluation; D012308:Risk Management / Q000458:organization & administration* / Q000706:statistics & numerical data; D013015:Sotalol / Q000008:administration & dosage / Q000009:adverse effects*; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects*; D016171:Torsades de Pointes / Q000139:chemically induced / Q000175:diagnosis / Q000453:epidemiology / Q000517:prevention & control*
D010627:Phenethylamines; D013449:Sulfonamides; D013015:Sotalol; C063533:dofetilide