Polypharmacy in Patients With Advanced Cancer and Pain. A European Cross-Sectional Study of 2282 Patients
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).
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.
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.
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.
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.