title: Contraindicated medications dispensed with cisapride: temporal trends in relation to the sending of 'Dear Doctor' letters.
abstract: OBJECTIVE
  'Dear Doctor' letters alert the prescribing community of drug labeling changes that contain new contraindications, warnings, adverse reactions, and precautions. There has been little assessment of the impact of these letters. We quantified the impact of two 'Dear Doctor' letters concerning interactions between cisapride and a series of drugs. A letter in 1995 described a risk of prolonged QT intervals and serious ventricular arrhythmia in patients who received macrolide antibiotics and imidazole antifungals in conjunction with cisapride. A June 1998 letter that expanded the list of contraindicated comedications had wider distribution than an earlier one, was accompanied by substantial Internet and media coverage, and was complemented by an effort to inform large pharmacy dispensing information organizations of the warnings against concurrent use of the named drugs.
  
  
  METHODS
  Health plan members with one or more outpatient pharmacy claims for cisapride during the period 1 January 1995 through 31 May 1999 were identified among members of a large New England health insurer. A retrospective review of concurrent and nearly concurrent dispensings of cisapride and contraindicated comedications was undertaken in the automated pharmacy claims data using both graphical and statistical time-series analysis. We tabulated by month the fraction of cisapride dispensings that occurred in close temporal relation to dispensings of contraindicated comedications. Codispensings that occurred on the same day were taken as the most direct measure of prescriber responsiveness to the letters. Codispensings that occurred in windows of plus or minus 2 weeks (29 day window) and plus or minus 4 weeks (57 day window) were taken as measures of possible simultaneous consumption. Among overlapping dispensings, we counted the proportion dispensed by the same pharmacy. Time series regression analysis of secular, seasonal, and step-effects was conducted.
  
  
  RESULTS
  There was a steady decline in codispensing of cisapride and contraindicated medicines, and a pronounced seasonal effect, arising principally from the seasonal use of macrolide antibiotics. Against this background, the isolated Dear Doctor letter of October 1995 had no discernible effect on prescribing practices. The 1998 letter and surrounding activity, by contrast, were followed by a 66% decline in same-day dispensings and a smaller, but still pronounced decline in dispensings in the wider time windows. For most codispensings of contraindicated medications with cisapride, both medications came from the same pharmacy.
  
  
  CONCLUSIONS
  Publicity and direct intervention with dispensing pharmacies may be an important supplement to Dear Doctor letters when the goal is to eliminate the codispensing of drugs that should not be taken together.
authors.affiliation: Ingenix Pharmaceutical Services, Epidemiology Division, One Newton Executive Park, Newton Lower Falls, MA 02462-1450, USA. lweatherby@epidemiology.com
authors.forename: L B
authors.initials: LB
authors.lastname: Weatherby
authors.forename: A M
authors.initials: AM
authors.lastname: Walker
authors.forename: D
authors.initials: D
authors.lastname: Fife
authors.forename: P
authors.initials: P
authors.lastname: Vervaet
authors.forename: M A
authors.initials: MA
authors.lastname: Klausner
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D020117:Cisapride; D003142:Communication; D000075202:Contraindications; D016208:Databases, Factual; D004347:Drug Interactions; D011307:Drug Prescriptions; D005260:Female; D005765:Gastrointestinal Agents; D006801:Humans; D007343:Insurance Carriers; D007348:Insurance, Health; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009511:New England
chemical_list: D005765:Gastrointestinal Agents; D020117:Cisapride