• Sebastian Frechen, Anna Zoeller, Klaus Ruberg, Raymond Voltz, and Jan Gaertner.
• Department of Palliative Care, Cologne University Hospital, Cologne, Germany. sebastian.frechen@uk-koeln.de
• Drug Saf. 2012 Sep 1; 35 (9): 745-58.

BackgroundPatients at the end of life often receive numerous medications for symptom management. In contrast to all other clinical situations, the aim of pharmacotherapy is strictly focused on quality of life.ObjectiveThe primary aims of this study were to assess the potential for drug-drug interactions (DDIs) in patients at the very end of life by identifying drug combinations and risk factors associated with a high risk of DDIs; and evaluate the clinical relevance of the potential DDIs in this unique patient population. Secondary objectives were to increase prescriber awareness and to derive a comprehensive framework for physicians to minimize DDIs in this specific setting of end-of-life care.Materials And MethodsCharts of 364 imminently dying inpatients of two hospices were reviewed retrospectively. Drugs prescribed during the last 2 weeks of life were screened for DDIs by the electronic database of the Federal Union of German Associations of Pharmacists, which classifies DDIs by therapeutic measures required to reduce possible adverse events according to the ORCA system (OpeRational ClAssification of Drug Interactions).ResultsPotential DDIs were detected in 223 patients (61%). In a multivariate analysis, polypharmacy was the major predictor for DDIs (odds ratio 1.5, 95% CI 1.4, 1.6). The drugs most commonly involved in therapeutically relevant potential DDIs were antipsychotics, antiemetics (e.g. metoclopramide, antihistamines), antidepressants, insulin, glucocorticoids, cardiovascular drugs and, in particular, NSAIDs. The most prevalent potential adverse effects were pharmacodynamically additive anticholinergic, antidopaminergic, cardiac (QT interval prolongation) and NSAID-associated toxicity (e.g. gastrointestinal, renal).ConclusionIn the context of end-of-life care, the clinical relevance of DDIs differs from other clinical settings. Most DDIs can be prevented if the prescribing physician considers a few therapeutic principles. Specifically, this concerns the awareness of futile and high-risk medications, as well as rational alternatives.

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