The annual cost of drug-related morbidity and
mortality in the United States has been estimated
at more than $136 billion.1 Adverse drug reactions
(ADRs) contribute significantly to these costs.2
Epidemiological studies indicate that ADRs occur in 5%
to 20% of all hospitalized patients,3,4 and that 3% to 28%
of all hospital admissions may be drug related.5-10
Adverse drug reactions and therapeutic failures can
be considered subsets of adverse drug outcomes. When
medication errors cause adverse drug outcomes, the
focus tends to be on errors of commission (ie, mistakes
in prescribing, dispensing, and/or administration of
drugs). For example, dispensing errors occur when
drugs have similar names (spelled or pronounced alike),
or when a misplaced decimal point results in the wrong
dosage. Medication errors, however, also can be errors of
omission. Errors of omission leading to ADRs or therapeutic
failures have been reported to include11:
An ADR or therapeutic drug failure involving 1 of the
above factors is considered to be preventable (ie, a medical
error). The adverse outcome could have been avoided
if optimal medical care and monitoring had been
The article by Raebel et al focuses on 1 of the leading
causes of preventable adverse drug outcomeslack of
therapeutic drug monitoring. In this epidemiological,
retrospective review, Raebel et al report on a cohort of
ambulatory patients whose therapy included drugs with
narrow therapeutic indices. Due to a direct concentration-effect relationship, these drugs provide therapeutic
benefits within a narrow range of concentrations. Below
that range, therapeutic failure can occur. Above that
range, serious ADRs can occur. Therapeutic drug monitoring,
especially with patients who seem to be more at
risk, may prevent adverse drug outcomes on both ends
of the drug-concentration relationship.
As a pharmacist educator and clinician focusing on
the identification, preventability, and analysis of ADRs,
I create an annual "top 10" list of drugs that lead to hospital
admissions at my practice site. It is always interesting
to see that just 10 drugs cause 40% to 60% of all
ADRs. Drugs on these lists (eg, warfarin, digoxin, phenytoin)
often have narrow therapeutic indices. Such drugs
require laboratory tests to determine the direct concentration-effect relationship. In nearly every case of hospitalization,
patients taking these drugs had toxic blood
levels. Had more adequate therapeutic drug monitoring
been performed, many of these hospitalizations might
have been avoided.
Raebel et al report a lack of therapeutic drug
monitoring involving certain drugs and certain patient
populations (eg, elderly, children). Fifty percent or more
of patients receiving drugs such as digoxin, theophylline,
procainamide, quinidine, or primidone did not
have therapeutic drug monitoring tests that would indicate
the plasma concentrations of these agents.
Although clinical implications (ie, hospitalizations,
emergency department and/or physician visits) were
not evaluated, this study does show that inadequate
monitoring of drugs with narrow therapeutic indices is a
substantial problem. This report may increase awareness
among physicians, pharmacists, and other clinicians, and encourage them to be more vigilant in monitoring
patients who take these agents as part of their
From Temple University School of Pharmacy, Philadelphia, Pa.
Address correspondence to: Patrick J. McDonnell, PharmD, Associate Professor of Clinical Pharmacy, Temple University School of Pharmacy, 3307 North Broad Street, Philadelphia, PA 19140. Email: firstname.lastname@example.org.
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