FDA Drug Information That Never Reaches Clinicians

Abstract

In their recent Perspective article (Oct. 29 issue),¹ Schwartz and Woloshin state that critical safety data were omitted from the first Zometa (zoledronic acid, Novartis) label, and they make several misleading statements that require clarification. Zometa was first approved for hypercalcemia of malignancy at a “maximum recommended” dose of 4 mg.² Although an 8-mg dose was tested in trials, clinical development of Zometa at this dose was discontinued when concerns arose about renal toxicity. The Food and Drug Administration (FDA) never approved the 8-mg dose. The authors incorrectly suggest that the first label's warnings about the 8-mg dose were inadequate; however, the label explicitly stated that “a single dose of Zometa should not exceed 4 mg” and that the risk of renal toxicity was significantly greater with 8 mg than with 4 mg.² The authors further claim that the exclusion of mortality data from the label was a grave omission; however, the FDA advisory panel on Zometa concluded that “although the incidence of death was higher in the Zometa 8-mg group, there was no discernable pattern or cause of death that suggested drug-relatedness.”² The FDA and Novartis included information in the label that they deemed critical in allowing physicians to make informed prescribing decisions.