Polypharmacy in Patients With Advanced Cancer and Pain. A European Cross-Sectional Study of 2282 Patients
Abstract
Context
Patients
with advanced cancer need multiple drugs to control symptoms and to
treat cancer and concomitant diseases. At the same time, the goal of
treatment changes as life expectancy becomes limited. This results in a
risk for polypharmacy, maintained use of unneeded drugs, and drug-drug
interactions (DDIs).
Objectives
The aim of the study was
to analyze the use of medications, and to identify unneeded drugs as
well as drugs and drug combinations with a risk for DDIs in a cohort of
advanced cancer pain patients, defined by a need for a World Health
Organization (WHO) analgesic ladder step III opioid.
Methods
All
drugs taken within a study day by cancer patients receiving opioids for
moderate or severe pain (step III opioids) were analyzed. Non-opioids
and adjuvants were analyzed for their use across countries. Unneeded
medications as well as drugs and drug combinations with a risk for
pharmacodynamic and pharmacokinetic DDIs were identified on the basis of
published literature and electronic resources.
Results
In
total, 2282 patients from 17 centers in 11 European countries were
included. They received a mean of 7.8 drugs (range 1-20). Over
one-quarter used 10 or more medications. The drugs and drug classes most
frequently co-administered with opioids were: proton pump inhibitors,
laxatives, corticosteroids, paracetamol (acetaminophen), nonsteroidal
anti-inflammatory drugs, metoclopramide, benzodiazepines,
anticoagulants, antibiotics, anticonvulsants, diuretics and
antidepressants. The use of non-opioids and essential adjuvants varied
across countries. Forty-five percent of patients received unnecessary or
potentially unnecessary drugs and about 7% were given duplicate or
antagonizing agents. Exposures to DDIs were frequent and increased the
risk of sedation, gastric ulcerations, bleedings, and neuropsychiatric
and cardiac complications. Many patients were exposed to pharmacokinetic
DDIs involving CYP450, including 58% who used a step III opioid CYP3A4
substrate, and more than 10% who were given major CYP3A4 inhibitors or
inducers.
Conclusion
Patients with cancer treated with a
WHO step III opioid use a high number of drugs. Non-opioid analgesics
and corticosteroids are frequently used, but different patterns of use
between countries were found. Many patients receive unneeded drugs and
are at risk of serious DDIs. These findings demonstrate that drug
therapy in these patients need to be evaluated continuously.
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