Drug Interactions Significantly Reduce Targeted Therapy Efficacy

The drug-drug interactions (DDI) between co-prescribed (Co-Rx) medications and targeted oral antineoplastic drugs (OAD) are associated with a significant decrease in effectiveness and increased toxicity, according to a study presented at the 2012 American Society for Clinical Pharmacology and Therapeutics Annual Meeting in National Harbor, MD.

The retrospective Medco Research Institute trial analyzed 11,600 patients’ drug interactions over the course of 12 months. The analysis included patients who had received 1 of 9 common CYP450 enzyme-targeted OADs and a Co-Rx medication that shared the same metabolic and transport pathways as the OAD.

The study found that the effectiveness of OADs was reduced by between 23% (sunitinib) and 57% (erlotinib) overall, while the toxicity of these agents was increased between 43% (erlotinib) and 74% (pazopanib). On average, 102 Co-Rx drugs were implicated in the reduction of effectiveness and 195 resulted in increased toxicity.

In general, the more enzymes an OAD targeted the more likely it was to have an interaction. The agent imatinib that targets the CYP450 enzymes 3A4, 1A2, 2D6, 2C9, and 2C19 experienced the largest number of Co-Rx drug related complications, including a total of 557 drugs that increased toxicity and 141 drugs that reduced efficacy.

“These high costs medications can have severe side effects and need to be actively monitored for proper use and adherence,” said Milayna Subar, MD, vice president and national practice leader at the Medco Oncology Therapeutic Resource Center. “What's as important is knowing what other medications the patient is on. The fact that about one quarter to 75 percent of patients on these oral drugs may not be getting the full benefit of their treatment or may in fact be putting their health at further risk because of another medication they are taking is concerning.”

The analysis found that primary care physicians (PCP) usually prescribed the DDI drug while an oncologist prescribed the OAD. Upon a closer examination of prescribing information for imatinib it was discovered that PCPs prescribed 49% of the DDI drugs and oncologists only 10%. Inversely, oncologists prescribed the agent imatinib in 64% of cases and PCPs in only 9%.

The authors suggested that these findings should serve as an impetus for oncologists and other physicians responsible for the care of patients to better communicate what they are prescribing.

Receiving multiple medications is common during oncology treatment and creates the potential to incur harmful complications. As the use of enzyme-targeted OADs continues to increase the need to investigate potentially harmful interactions becomes more important.