Drug interactions in palliative care - it's more than cytochrome P450

Objective: This study aims to identify the combination of substances with high potential for drug interactions in a palliative care setting and to provide concise recommendations for physicians. Methods: We used a retrospective systematic chart analysis of 200 consecutive inpatients. The recently developed and internationally advocated classification system OpeRational ClAssification of Drug Interactions was applied using the national database of the Federal Union of German Associations of Pharmacists. Charts of patients with potential for severe DDIs were examined manually for clinical relevance. Results: In 151 patients (75%) a total of 631 potential drug interactions were identified. Opioids (exception: methadone), non-opioids (exception: non-steroidal anti-inflammatory drugs), benzodiazepines, proton-pump inhibitors, laxatives, co-analgesics (exception: carbamazepine) and butylscopolamine were generally safe. High potential for drug interactions included combinations of scopolamine, neuroleptics, metoclopramide, antihistamines, non-steroidal anti-inflammatory drugs, (levo-) methadone, amitriptyline, carbamazepine and diuretics. The manual analyses of records from eight patients with risk for severe drug interactions provided no indicator for clinical relevance in these specific patients. Drug interactions attributed to the cytochrome pathway played a minor role (exception: carbamazepine). Conclusion: Most relevant drug interactions can be expected with: (i) drugs (inter-) acting via histamine, acetylcholine or dopamine receptors; and (ii) Non-steroidal anti-inflammatory drugs. Even in last hours of life the combination of substances (e.g. anticholinergics) may produce relevant drug interactions (e.g. delirium). Perspective: Data on the potential for drug-drug interactions in palliative case is extremely scarce, but drug interactions can be limited if a few facts are considered. A synopsis of the findings of these studies is presented as concise recommendation to minimize drug interactions.