Tardive dyskinesia risks and metoclopramide use before and after U.S. market withdrawal of cisapride.
OBJECTIVE
To assess risk factors for tardive dyskinesia (TD) in spontaneous reports of metoclopramide and TD and evaluate metoclopramide prescribing patterns before and after withdrawal of cisapride from the market in the United States.


METHODS
Retrospective and observational analyses.


METHODS
International metoclopramide adverse event reports and domestic drug-use data for the continental United States.


METHODS
Users of metoclopramide for 30 days or more who experienced adverse events reported as TD.


METHODS
Analyses of the Food and Drug Administration Adverse Event Reporting System (AERS) and IMS HEALTH data.


METHODS
Pharmacoepidemiological patterns in AERS reports and utilization data from IMS HEALTH.


RESULTS
The case series comprised 87 reports of primarily older (mean+/-SD, 60+/-22 years ) women (67% of all cases). While average metoclopramide daily dose (33+/-14 mg) was within recommended product labeling limits, duration of use was considerably longer (753+/-951 days). Overall, 37% of the reports included concomitant drugs believed to be TD risk factors. Similarly, 18% of the reports noted comorbid diseases that are considered risk factors for development of TD. Metoclopramide utilization decreased following cisapride marketing in 1993 and increased following cisapride withdrawal in 2000. The majority (62%) of metoclopramide prescriptions were intended for women. Intended use overall increased with age and was highest in the seventh and eighth decades, with nearly one quarter of all utilization being in persons older than 70 years.


CONCLUSIONS
Well-described TD risk factors were common in metoclopramide-associated TD reports. Given the cisapride market withdrawal and associated increased metoclopramide utilization, the incidence of TD may increase accordingly. TD risk factors relative to the intended benefit and duration of use should be considered in metoclopramide prescribing.
Shaffer
Douglas
D
Center for Drug Evaluation and Research, US Food and Drug Administration, Rockville, MD 20857, USA.
Butterfield
Marian
M
Pamer
Carol
C
Mackey
Ann Corken
AC
D000293:Adolescent; D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems; D000368:Aged; D000369:Aged, 80 and over; D017109:Akathisia, Drug-Induced / Q000209:etiology*; D002648:Child; D002675:Child, Preschool; D020117:Cisapride / Q000008:administration & dosage / Q000009:adverse effects*; D004363:Drug Utilization; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008787:Metoclopramide / Q000008:administration & dosage / Q000009:adverse effects*; D008875:Middle Aged; D012189:Retrospective Studies; D012307:Risk Factors; D014481:United States; D014486:United States Food and Drug Administration
D008787:Metoclopramide; D020117:Cisapride