Drug combinations have the potential to interact, sometimes with deleterious effects, and patients with cancer face a real risk for such drug interactions that have clinical consequences, according to new findings.
In a cohort of 149 patients with cancer, 36 potentially clinically relevant drug-to-drug interactions (DDIs) were identified in 26 patients (17.4%), and all of them required the patient to modify therapy.
In addition, more than half of the cohort reported using herbal supplements during their cancer therapy, and 122 possible herb-to-drug interactions (HDIs) were detected.
The study results were published online June 19 in the Journal of Oncology Practice.
Importantly, the investigation also documented several likely actual interactions, which distinguishes the research from past efforts. "Our analysis showed that 2.7% of patients were actually experiencing possible adverse drug reactions as a consequence of a DDI," write the authors, led by Allan Ramos-Esquivel, MD, MSc, from the Department of Medical Oncology, Hospital San Juan de Dios, San Jose, Costa Rica.
Prior research has only revealed "potential and theoretic DDIs," the authors note. "However, the study design of this trial allowed for a week of clinical observation before the notification of any potential DDIs by pharmacists."
The team reports that four patients (2.7%) experienced possible clinical consequences as a result of a DDI: Two patients had higher-than-anticipated toxicity as a result of using either methotrexate and ibuprofen together or imatinib together with acetaminophen; a third patient experienced international normalized ratio values that were above the therapeutic range when warfarin was used with sorafenib; and the fourth patient had toxic plasma levels of phenytoin, an antiseizure drug, after using capecitabine.
Many patients with cancer receive treatment for other conditions, and thus DDIs pose a threat of undesired adverse events, as well as increased or decreased efficacy of the antineoplastic agents.
For example, a recent study reported that proton-pump inhibitors may impair the activity of the oral chemotherapeutic agent capecitabine (Xeloda, Roche).
Among older patients, who make up about 70% of the cancer population, treatment can be particularly complicated because of the higher rate of comorbidities and the use of multiple medications.
Drug interactions in oncology are of particular concern, the authors emphasize, because of the narrow-therapeutic-index anticancer agents and their inherent toxicity.
Another concern is the interaction between anticancer agents and complementary and alternative medicine (CAM). One large survey found that 47% of patients with cancer have used CAM, but most respondents (80%) did not have a healthcare professional speak to them about it. Notably, 70% of surveyed practitioners stated that they were not prepared to monitor the use of those products.
For the current study, Dr Ramos-Esquivel and his colleagues conducted a prospective trial in ambulatory patients with cancer who were treated with oral and/or intravenous drugs at the San Juan de Dios Hospital in Costa Rica, with the goal of identifying "clinically relevant" herb and drug interactions that would lead to a pharmaceutical intervention.
All participants completed a questionnaire that identified concomitant use of any over-the-counter drug or herbal supplement, and then potential interactions were identified by using two different databases. If the pharmacist identified a potentially clinically relevant DDI, the oncologist was notified with a suggested intervention.
Of the 149 participants, 81 (54.4%) had comorbid conditions, including high blood pressure (n = 57), diabetes (n = 21), hypothyroidism (n = 10), and dyslipidemia (n = 8). The median number of comorbidities for each patient was 1 (range, 0 to 5), and the cohort as a whole used a total of 32 different oncologic therapeutics.
The median number of concomitant drugs for each patient was 3 (range, 0 to 13 drugs).
Among the patients who experienced a DDI, pharmacokinetics was the most frequent mechanism of interaction (86.1%), followed by pharmacodynamics (13.9%).
When the researchers looked at HDIs, the median number of herbal supplements taken by each patient was 4 (range, 0 to 8 supplements). Of the reported interactions (122 in 75 patients), 75 (61.4%) were considered to be moderate, 3 (2.5%) were mild, and 44 were not graded because of a lack of clinical data. However, no clinical consequences were reported as a result of these interactions.
"Our study showed that a program of medication surveillance in patients with cancer led by clinical pharmacists could prevent a relatively high proportion of patients from experiencing the potentially adverse clinical consequences of DDIs and HDIs," write the authors. "Additional studies are needed to better identify real drug interactions and the financial impact on health services."
Dr Ramos-Esquivel declares financial relationships with Roche, Bayer, and Asofarma. The other authors have disclosed no relevant financial relationships.
J Oncol Pract. Published online July 19, 2017. Abstract
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