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Purpose: Azithromycin is a common first-line antibiotic for respiratory infection; however, there is conflicting evidence regarding risk of cardiovascular death. We assessed cardiovascular and noncardiovascular mortality associated with azithromycin versus amoxicillin-clavulanate among US Veterans treated for nonear-nose-throat respiratory infection ("respiratory") or ear-nose-throat infection indication., Methods: Electronic health record data from the US Veterans Health Administration database were used to identify Veterans (30-74 years) with outpatient dispensings of oral azithromycin versus amoxicillin-clavulanate for respiratory or ear-nose-throat infection (January 01, 2000-December 31, 2014). Outcomes assessed were risk of cardiovascular death and noncardiovascular death within 1-5 and 6-10 days postdispensing. Inverse probability of treatment-weighted proportional hazards models and binomial regression models were used to estimate hazard ratios (HRs) and compute risk differences (RD) per million courses of therapy. Cardiac death (subset of cardiovascular death) was assessed in sensitivity analyses., Results: There were 629 345 azithromycin and 168 429 amoxicillin-clavulanate dispensings for respiratory indications, 143 783 azithromycin, and 203 142 amoxicillin-clavulanate dispensings for ear-nose-throat indications. For respiratory indications, azithromycin was not associated with a significantly different risk of cardiovascular death versus amoxicillin-clavulanate within 1-5 days postdispensing (HR [95% confidence interval (CI)]: 1.12 [0.63, 2.00]; RD [95% CI]: 11 [-43, 64] deaths/million courses of therapy). No elevated risk for azithromycin was found for ear-nose-throat indications. Pooled results for both indications via meta-analysis showed no association between antibiotics and cardiovascular mortality. There was no significant difference in risk of noncardiovascular or cardiac death between antibiotics postdispensing., Conclusion: Azithromycin was not associated with elevated risk of cardiovascular or noncardiovascular death versus amoxicillin-clavulanate among US Veterans., (© 2022 John Wiley & Sons Ltd.)

Objectives: The Food and Drug Administration and pharmaceutical manufacturers use "Dear doctor" letters to alert physicians about drug safety. To determine how such warnings may be improved, we retrospectively examined how variations in the wording of one series of "Dear doctor" letters affected their impact on concomitant dispensing of cisapride (Propulsid; Janssen Pharmaceutica, Titusville, NJ) and several medications contraindicated for concomitant use., Methods: Concomitant dispensing was defined as dispensing cisapride and a contraindicated medication on dates when the intended duration of the two dispensings overlapped on at least 1 day. Using outpatient pharmacy claims from a New England health insurer, we calculated a concomitant dispensing rate for each calendar month as the number of concomitant cisapride dispensings divided by the total number of cisapride dispensings. We grouped drugs contraindicated for concomitant use with cisapride as (1) explicitly named in the warnings, (2) only mentioned as examples of a drug class, or (3) only implied as drug class members. We used multivariate analysis to relate temporal changes in concomitant dispensing rates to type of warning (explicit, example, or implied), patient demographic characteristics, season, calendar year, and temporal relationship to the "Dear doctor" warnings., Results: A highly publicized letter sent in June 1998 was associated with a notable decline (58%) in the concomitant dispensing rate with explicitly contraindicated drugs but not in the concomitant dispensing of cisapride with the example or implied drugs. An earlier letter, which had been explicit but was accompanied by less publicity, had no measurable effect on this study's measure of coprescription, nor did a later letter that emphasized comorbidities., Conclusions: Explicit, well-publicized drug warnings can change prescriber behavior.