Polypharmacy in patients with advanced cancer and pain: a European cross-sectional study of 2282 patients.
BACKGROUND
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).


OBJECTIVE
The aim of the study was to analyze the use of medications and to identify unneeded drugs, and 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 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. Nonopioids and adjuvants were analyzed for their use across countries. Unneeded medications and 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 coadministered 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 nonopioids and essential adjuvants varied across countries. Approximately 45% 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 cytochrome P450, including about 58% who used a Step III opioid CYP3A4 (izoenzyme of cytochrome P450) substrate, and more than 10% who were given major CYP3A4 inhibitors or inducers.


CONCLUSIONS
Patients with cancer treated with a World Health Organization Step III opioid use a high number of drugs. Nonopioid 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 needs to be evaluated continuously.
Department of Palliative Medicine Karol Marcinkowski University of Medical Sciences, Poznan, Poland; Hospice Palium, University Hospital of the Lord's Transfiguration, Poznan, Poland. Electronic address: alemieszek@ump.edu.pl.
Aleksandra
A
Kotlinska-Lemieszek
Palliative Care Unit, Department of Medicine, Telemark Hospital Trust, Skien, Norway; European Palliative Care Research Centre, Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
Ornulf
O
Paulsen
European Palliative Care Research Centre, Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway; Department of Oncology, St Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
Stein
S
Kaasa
Department of Circulation and Medical Imaging, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway; Department of Anaesthesiology and Intensive Care Medicine, St Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
Pål
P
Klepstad
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000701:Analgesics, Opioid / Q000627:therapeutic use; D017024:Chemotherapy, Adjuvant / Q000706:statistics & numerical data; D003430:Cross-Sectional Studies; D005060:Europe; D005260:Female; D006801:Humans; D057970:Inappropriate Prescribing / Q000706:statistics & numerical data; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000503:physiopathology*; D010146:Pain / Q000188:drug therapy* / Q000503:physiopathology*; D019338:Polypharmacy; D055815:Young Adult
D000701:Analgesics, Opioid
Pharmacotherapy; adjuvants; cancer pain; coanalgesics; drug-drug interactions; nonopioids; opioids; palliative care; polypharmacy; unnecessary drugs; unneeded drugs