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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
Jay S. Cohen, MD
Arch Intern Med. 2001;161:957-964.
Background Adverse drug events (ADEs) are a major cause of morbidity and mortality,
and even minor ADEs may adversely affect patients' compliance with treatment.
Because most ADEs are dose-related phenomena, adjusting drug dosages to account
for individual patients' needs and tolerances is fundamental to good therapeutics.
Objective To determine whether the Physicians' Desk Reference (PDR), the leading source of drug information
for physicians, provides the full range of effective drug doses, especially
the lowest, least ADE-prone doses of medications, for physicians to consider
in treating patients.
Methods Review of dosage guidelines and dose-response information in the PDR. Comparison with dose-response data obtained from articles
listed in MEDLINE from 1966 to 2000.
Results For many types of medications, physicians are frequently advised to
use the lowest effective doses of drugs, especially initially. Yet, effective
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 comprehensive information.
However, the PDR contains only the limited dose information
from package inserts. Because the PDR was originally
developed as a promotional device, there is no mechanism by which all clinically
relevant dose-response data or important postrelease discoveries are regularly
and rapidly incorporated into it. Thus, a gap exists in the availability of
current and comprehensive dose information for physicians. This article provides
information on lower, effective doses for 48 major medications, with an extensive
reference list—a compilation of low-dose information not previously
published, to our knowledge, in the medical literature. Physicians must have
a readily accessible source of current and complete dose-response information
to individualize drug therapy and minimize the risks of ADEs.
From the Departments of Family and Preventive Medicine and Psychiatry,
University of California, San Diego, La Jolla.
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