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Clinically significant drug interactions at end of life

Abstract Potential drug interactions encountered at the end of life may be cumbersome to predict and have significant impact on the palliation of symptoms. Recent advances in identifying metabolic pathways and metabolites of frequently used medications allow clinicians to consider the fate and pharmacodynamic effects of drugs prescribed. Numerous medications used in the palliative care population undergo hepatic and extrahepatic metabolism to active and inactive metabolites. Hepatic reactions rendering medications prepared for excretion or removal from the system are complex, but may be summarised for medications frequently used in end-of-life care as Phase 1 oxidation, hydroxylation, and reduction reactions, and Phase 2 glucuronidation reactions. Both general types of drug metabolism pathways may be altered by medications, disease states, and normal ageing processes. Specific to end-of-life care, Phase 1 reactions may become less robust, while Phase 2 reactions are typically preserved. Benzodiazepines, opioids, non-opioid analgesics, and hypnotics may all exhibit additive or reduced efficacy when given concurrently with medications which inhibit or induce these pathways. Unexpected dose-related toxicity or adverse effects may also manifest. In summary, understanding and anticipating potential drug interactions in end of life and palliative care is paramount for the health professional.