Contraindicated use of cisapride: impact of food and drug administration regulatory action.
BACKGROUND
Cisapride, a gastrointestinal tract promotility agent, can cause life-threatening cardiac arrhythmias in patients susceptible either because of concurrent use of medications that interfere with cisapride metabolism or prolong the QT interval or because of the presence of other diseases that predispose to such arrhythmias. In June 1998, the US Food and Drug Administration (FDA) determined that use of cisapride was contraindicated in such patients and informed practitioners through additions to the boxed warning in the label and a "Dear Health Care Professional" letter sent by the drug's manufacturer.


OBJECTIVE
To evaluate the impact of the FDA's 1998 regulatory action regarding contraindicated use of cisapride.


METHODS
Analysis of data for the 1-year periods before (July 1997-June 1998) and after (July 1998-June 1999) the regulatory action from the population-based, pharmacoepidemiology research databases of 2 managed care organizations (sites A and B) and a state Medicaid program (site C).


METHODS
Patients with at least 180 days of prior enrollment in 1 of the 3 sites who were prescribed cisapride at least once in the period before (n = 24 840) or after (n = 22 459) regulatory action. Patients could be included in both cohorts.


METHODS
Proportion of cisapride users in each period for whom cisapride use was contraindicated by the product label, based on computerized patient medical encounter records.


RESULTS
In the year prior to regulatory action, cisapride use was contraindicated for 26%, 30%, and 60% of users in study sites A, B, and C, respectively. In the year after regulatory action, use was contraindicated for 24%, 28%, and 58% of users, a reduction in contraindicated use of approximately 2 per 100 cisapride users at each site. When the analysis was restricted to new users of cisapride after regulatory action, only minor reductions in contraindicated use were found.


CONCLUSIONS
The FDA's 1998 regulatory action regarding cisapride use had no material effect on contraindicated cisapride use. More effective ways to communicate new information about drug safety are needed.
Smalley
W
W
Department of Preventive Medicine, Medical Center North, A-1124, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Shatin
D
D
Wysowski
D K
DK
Gurwitz
J
J
Andrade
S E
SE
Goodman
M
M
Chan
K A
KA
Platt
R
R
Schech
S D
SD
Ray
W A
WA
D020117:Cisapride / Q000009:adverse effects; D015331:Cohort Studies; D000075202:Contraindications; D004348:Drug Labeling; D011307:Drug Prescriptions; D005765:Gastrointestinal Agents / Q000009:adverse effects; D006801:Humans; D007880:Legislation, Drug; D014481:United States; D014486:United States Food and Drug Administration
D005765:Gastrointestinal Agents; D020117:Cisapride