Drug interactions plague elderly cancer patients

Adverse drug reaction increases six-fold from the second decade to the eighth decade of life, from 10 adverse events per 10,000 persons to 60 per 10,000. This is especially important to oncology patients. J.F. Knudsen, PhD, MD, a research associate at New Hope Cancer Center in Hudson, Fla., and other researchers performed a retrospective cohort study on cancer patients at a community-based, university-affiliated medical practice who had multiple comorbidities. The researchers determined the potential for adverse reactions and also physicians' responses to risk arising from drug interactions.

At the time of the survey in 2006, the patients took an average of 9.1 prescription and nonprescription drugs, and they took an average of three chemotherapy and supportive drugs.

Surprisingly, the oncologists failed to modify treatment when alerted to potential drug-drug interactions. They acknowledged little communication with pharmacists regarding their patients' drug burden and potential for interactions, even though software to alert for drug interactions was in place in the pharmacies.

Also, physicians cited a lack of pharmacokinetic and pharmacodynamic guidance from which to modify drug protocols, confidence in their ability to manage various degrees of toxicity, and disinterest in deviating from published standard-of-care regimens.

"Oncologic practices could be a lot safer if doctors realized the drug-drug interactions and developed guidelines to mitigate impact," says Knudsen. "If you look at hospital admissions secondary to side effects from chemotherapy, the impact is monumental. Managed care can be alert to drug-drug interactions by supporting patients through appropriate interventions that can alleviate the effects of toxicity," says Knudsen.

Vigilance at all levels of care can provide a better understanding of the interactions between comorbid conditions in patients with cancer.

Overview of potential pharmacokinetic interactions

Drug absorption, distribution, metabolism, and elimination change with age. Little guidance is available regarding drug interaction in the elderly oncology patient.

Compound Relevant enzyme P-glycoprotein substrate Elimination In vitro protein binding
Carboplatin Renal Not bound
Paclitaxel CYP 2C8, CYP 3A + Liver 89–98 %
Fluorouracil DPD 0 Liver Unknown
Leucovorin 0 Unknown Unknown
Rituximab 0 Unknown Unknown
Cyclophosphamide CYP 2C9 0 Metabolism (25 % in urine) Low
Cisplatin CYP 3A4/CYP 2B6 0 Renal 90%
Etopside CYP 3A + Biliary 97%
Doxorubicin CYP 3A5 + Biliary 75%
Source: Sokol KC, et al. Polypharmacy in older oncology patients and the need for an interdisciplinary approach to side-effect management. J Clin Pharm and Ther. 2007;32:169–175.

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