Dose discrepancies between the Physicians' Desk Reference and the medical literature, and their possible role in the high incidence of dose-related adverse drug events

Background: Adverse drug events (ADEs) are a major cause of morbidity and m ortality, and even minor ADEs may adversely affect patients' compliance wit h treatment. Because most ADEs are dose-related phenomena, adjusting drug d osages to account for individual patients' needs and tolerances is fundamen tal to good therapeutics. Objective: To determine whether the Physicians' Desk Reference (PDR), the l eading source of drug information for physicians, provides the full range o f effective drug doses, especially the lowest, least ADE-prone doses of med ications, for physicians to consider in treating patients. Methods: Review of dosage guidelines and dose-response information in the P DR. Comparison with dose-response data obtained from articles listed in MED LINE from 1966 to 2000. Results: For many types of medications, physicians are frequently advised t o use the lowest effective doses of drugs, especially initially. Yet, effec tive low doses determined in prerelease studies or in postrelease work are often omitted from the PDR, even when they have been recommended by expert panels. Conclusions: Optimal therapeutics depends on the availability of comprehens ive information. However, the PDR contains only the limited dose informatio n from package inserts. Because the PDR was originally developed as a promo tional device, there is no mechanism by which all clinically relevant dose- response data or important postrelease discoveries are regularly and rapidl y incorporated into it. Thus, a gap exists in the availability of current a nd comprehensive dose information for physicians. This article provides inf ormation on lower, effective doses for 48 major medications, with an extens ive reference list-a compilation of low-dose information not previously pub lished, to our knowledge, in the medical literature. Physicians must have a readily accessible source of current and complete dose-response informatio n to individualize drug therapy and minimize the risks of ADEs.