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http://www.medscape.com/viewarticle/557261
From Journal of the National Cancer Institute
Potential Drug Interactions and Duplicate Prescriptions Among Cancer
Patients
Posted 06/01/2007
Rachel P. Riechelmann; Ian F. Tannock; Lisa Wang; Everardo D. Saad; Nathan
A. Taback; Monika K. Krzyzanowska
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Abstract and Introduction
Abstract
Background: Cancer patients receive numerous medications, including
antineoplastic agents, drugs for supportive care, and medications for
comorbid illnesses. Therefore, they are at risk for drug interactions and
duplicate prescribing.
Methods: A questionnaire eliciting information on demographics and
medications taken in the previous 4 weeks was given to adult outpatients
receiving systemic anticancer therapy for solid tumors. The Drug
Interaction Facts software, version 4.0, was used to identify potential
drug interactions and to classify them by level of severity (major,
moderate, or minor) and the strength of scientific evidence for them
(using categories [1-5] of decreasing certainty). Summary statistics and
logistic regression were used to analyze the data. All statistical tests
were two-sided.
Results: The survey was completed by 405 patients. We observed 276
potential drug interactions, and at least one potential interaction was
identified in 109 patients (27%; 95% confidence interval [CI] = 23% to
31%). Of the potential interactions, 25 (9%) were classified as major and
211 (77%) as moderate. Nearly half (49%) of potential interactions were
supported by level 1 or 2 scientific evidence. Most potential drug
interactions (87%) involved non-anticancer agents such as
warfarin,
antihypertensive drugs, corticosteroids, and anticonvulsants, but some (n
= 36, 13%) involved antineoplastic agents. In multivariable analysis,
increased risk of receiving drug combinations in which there were
potential drug interactions was associated with receipt of increasing
numbers of drugs (odds ratio [OR] = 1.4 per additional drug, 95% CI = 1.26
to 1.58, P<.001 from the Wald chi-square test), type of medication (drugs
to treat comorbid conditions versus supportive care medications only; OR =
8.6, 95% CI = 2.9 to 25, P<.001), and the presence of brain tumors.
Thirty-two (8%) patients were exposed to duplicate medications, most often
corticosteroids, proton pump inhibitors, or benzodiazepines.
Conclusion: Potential drug interactions were common among cancer patients
and most often involved medications to treat comorbid conditions.
Duplicate medications were infrequent.
Introduction
Cancer patients are particularly susceptible to drug interactions. One
reason is that they often receive multiple medications—in addition to
antineoplastic agents and drugs to treat comorbid conditions, cancer
patients may receive medications to treat both therapy-induced toxicity
and cancer-related syndromes, such as pain, seizures, and venous
thrombosis. The risk of drug interactions is further heightened because
the cancer patient's pharmacokinetic parameters may be altered. The change
in pharmacokinetic parameters may be due to a number of factors: impaired
drug absorption due to mucositis and malnutrition, variation in a drug's
volume of distribution because of reduced levels of serum-binding proteins
and generalized edema, or, in patients with renal and/or hepatic
dysfunction, altered drug excretion.
There are three types of drug interactions: pharmacodynamic,
pharmacokinetic, and pharmaceutical.[1] Pharmacodynamic interactions
usually result from combining two drugs with similar mechanisms of action
(in which case they may behave in synergistic, additive, or antagonistic
fashion) or when an electrolytic abnormality induced by one drug alters
the net effect of another. A pharmacokinetic interaction takes place when
a drug alters the absorption, distribution, metabolism, and/or excretion
of another drug. Pharmacokinetic interactions via metabolic effects most
often occur via drug interactions with cytochrome P450 enzymes;
antineoplastic medications that are entirely or partly metabolized by such
enzymes include cyclophosphamide, taxanes, etoposide, irinotecan,
aromatase inhibitors, vinca alkaloids, bicalutamide, imatinib, gefitinib,
and erlotinib.[2-7] A pharmaceutical interaction occurs when two
chemically incompatible drugs are mixed before intravenous administration
resulting in inactivation of one or both drugs.[1]
Several studies have evaluated the potential for drug interactions in
general medicine. It was found in large surveys that approximately 60% of
inpatients in general medical wards were at risk of drug
interactions,[8-10] and studies conducted in hospital emergency
departments found that from 16% to 47% of patients were at risk of drug
interactions.[11-13] Among 103 outpatients screened by their family
physician for the presence of drug combinations in which there was a
potential for interaction, almost 70% had been exposed to such
combinations.[14] An analysis of more than 5 million prescriptions in the
French national healthcare system found that 2% of outpatients were
exposed to either absolutely or relatively contraindicated drug
combinations.[15] Finally, in a hospital-based retrospective study
conducted in Norway, 18% of 732 deaths were associated, either directly or
indirectly, with drug interactions.[16]
By contrast, few studies have addressed drug interactions in patients with
cancer. In the Norwegian study,[17] 4% of cancer-related deaths in
hospitalized patients were associated with severe drug interactions.[16]
In a previous study, we evaluated the frequency of drug combinations with
potential to interact in cancer patients, but that study included only
inpatients not currently receiving anticancer therapy.[17] We found that
63% of patients were exposed to drug combinations in which there was a
potential for interaction. Because of the possible negative impact of drug
interactions on patients and the paucity of literature on this topic in
patients with cancer, we designed a cross-sectional study to evaluate the
epidemiology of exposure to drugs with a potential to interact among
ambulatory cancer patients receiving systemic anticancer therapy. The
secondary objective was to evaluate the frequency and risk factors for
duplicate prescribing in this population.
Section 1 of 4
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