Contraindicated medications dispensed with cisapride: temporal trends in relation to the sending of 'Dear Doctor' letters

Purpose 'Dear Doctor' letters alert the prescribing community of drug label ing 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 i nteractions between cisapride and a series of drugs. A letter in 1995 descr ibed a risk of prolonged QT intervals and serious ventricular arrhythmia in patients who received macrolide antibiotics and imidazole antifungals in c onjunction with cisapride. A June 1998 letter that expanded the list of con traindicated comedications had wider distribution than an earlier one, was accompanied by substantial Internet and media coverage, and was complemente d by an effort to inform large pharmacy dispensing information organization s 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 I January 1995 through 31 May 1999 were identi fied among members of a large New England health insurer. A retrospective r eview of concurrent and nearly concurrent dispensings of cisapride and cont raindicated comedications was undertaken in the automated pharmacy claims d ata using both graphical and statistical time-series analysis. We tabulated by month the fraction of cisapride dispensings that occurred in close temp oral relation to dispensings of contraindicated comedications. Codispensing s that occurred on the same day were taken as the most direct measure of pr escriber responsiveness to the letters. Codispensings that occurred in wind ows 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. Am ong overlapping dispensings, we counted the proportion dispensed by the sam e pharmacy. Time series regression analysis of secular, seasonal, and step- effects was conducted. Results There was a steady decline in codispensing of cisapride and contrai ndicated medicines, and a pronounced seasonal effect, arising principally f rom the seasonal use of macrolide antibiotics. Against this background, the isolated Dear Doctor letter of October 1995 had no discernible effect on p rescribing 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 mos t codispensings of contraindicated medications with cisapride, both medicat ions came from the same pharmacy. Conclusions Publicity and direct intervention with dispensing pharmacies ma y be an important supplement to Dear Doctor letters when the goal is to eli minate the codispensing of drugs that should not be taken together.