Controlling Adverse Drug Reactions Through Improved Monitoring

The annual cost of drug-related morbidity andmortality in the United States has been estimatedat more than $136 billion.¹ Adverse drug reactions(ADRs) contribute significantly to these costs.²Epidemiological 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 canbe considered subsets of adverse drug outcomes. Whenmedication errors cause adverse drug outcomes, thefocus tends to be on errors of commission (ie, mistakesin prescribing, dispensing, and/or administration ofdrugs). For example, dispensing errors occur whendrugs have similar names (spelled or pronounced alike),or when a misplaced decimal point results in the wrongdosage. Medication errors, however, also can be errors ofomission. Errors of omission leading to ADRs or therapeuticfailures have been reported to include¹¹:

• Drugs considered to be inappropriate for thepatient's condition (ie, because of contraindications,comorbid disease states, or dose adjustmentsfor renal insufficiency).
• Dosage or frequency of administration consideredinappropriate for the patient's condition.
• Previous history of an allergy or adverse reactionto the drug.
• Drug interactions.
• Poor patient compliance.
• Incomplete or inadequate monitoring of drugtherapy.

An ADR or therapeutic drug failure involving 1 of theabove factors is considered to be preventable (ie, a medicalerror). The adverse outcome could have been avoidedif optimal medical care and monitoring had beenprovided.

The article by Raebel et al focuses on 1 of the leadingcauses of preventable adverse drug outcomes—lack oftherapeutic drug monitoring. In this epidemiological,retrospective review, Raebel et al report on a cohort ofambulatory patients whose therapy included drugs withnarrow therapeutic indices. Due to a direct concentration-effect relationship, these drugs provide therapeuticbenefits within a narrow range of concentrations. Belowthat range, therapeutic failure can occur. Above thatrange, serious ADRs can occur. Therapeutic drug monitoring,especially with patients who seem to be more atrisk, may prevent adverse drug outcomes on both endsof the drug-concentration relationship.

As a pharmacist educator and clinician focusing onthe identification, preventability, and analysis of ADRs,I create an annual "top 10" list of drugs that lead to hospitaladmissions at my practice site. It is always interestingto see that just 10 drugs cause 40% to 60% of allADRs. Drugs on these lists (eg, warfarin, digoxin, phenytoin)often have narrow therapeutic indices. Such drugsrequire laboratory tests to determine the direct concentration-effect relationship. In nearly every case of hospitalization,patients taking these drugs had toxic bloodlevels. Had more adequate therapeutic drug monitoringbeen performed, many of these hospitalizations mighthave been avoided.

Raebel et al report a lack of therapeutic drugmonitoring involving certain drugs and certain patientpopulations (eg, elderly, children). Fifty percent or moreof patients receiving drugs such as digoxin, theophylline,procainamide, quinidine, or primidone did nothave therapeutic drug monitoring tests that would indicatethe plasma concentrations of these agents.Although clinical implications (ie, hospitalizations,emergency department and/or physician visits) werenot evaluated, this study does show that inadequatemonitoring of drugs with narrow therapeutic indices is asubstantial problem. This report may increase awarenessamong physicians, pharmacists, and other clinicians, and encourage them to be more vigilant in monitoringpatients who take these agents as part of theirdrug therapy.

From Temple University School of Pharmacy, Philadelphia, Pa.

Address correspondence to: Patrick J. McDonnell, PharmD, Associate Professor ofClinical Pharmacy, Temple University School of Pharmacy, 3307 North Broad Street,Philadelphia, PA 19140. Email: patrick.mcdonnell@temple.edu.

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