Toxicity and Drug–Drug Interactions

A multicenter study of 296 patients with CML demonstrated that hematologic and nonhematologic toxicities were similar among patients with or without polypharmacy.10 Similarly, a study of 229 elderly patients with head and neck cancer found no association between polypharmacy and treatment-related toxicity, but also determined polypharmacy was associated with an increase in noncancer health events (OR, 1.81; 95% CI, 0.99-3.31).11 A study of 500 patients aged 65 or older undergoing chemotherapy found no association between the number of daily medications or PIM use and toxicity or hospitalization.12

However, a study of 172 patients with cancer receiving irinotecan-based chemotherapy found that concomitant medication use was significantly associated with irinotecan-associated severe neutropenia and diarrhea.13 Increasing the number of concomitant medications was associated with an increase in the incidence of severe irinotecan-related toxicities. Another study found that polypharmacy was associated with toxicity among 73 evaluable elderly patients with metastatic breast cancer.14 Drug-related problems occurred in 77.6% of patients within a cohort of elderly patients with cancer, and the use of 5 or more medications was significantly associated with an increased risk of drug-related problems (OR, 1.862; P = .039).15

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Not surprisingly, the risk of drug-drug interactions (DDIs) increases with the number of medications administered.1 In a study of 445 elderly patients with cancer, severe drug interactions occurred in 35.1% of patients and severe drug interactions were significantly associated with polypharmacy (P < .05).16 A small study of 20 patients taking erlotinib for non-small cell lung cancer found that 55% of patients were also taking a proton pump inhibitor, which is contraindicated due to impaired absorption of erlotinib.17

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There are few studies that evaluate the effect of polypharmacy on cancer-related mortality or other outcomes. Current studies show mixed results and definitive conclusions about the impact of polypharmacy on outcomes have not been established. Although polypharmacy is associated with PIM use, it is important that clinicians carefully evaluate every medication prescribed to their patient to determine if the benefits of coadministering certain medications outweigh the risks.


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