Drug-drug interactions in patients treated for cancer: a prospective study on clinical interventions.

BACKGROUND Drug-drug interactions (DDIs) are of major concern in oncology, since cancer patients typically take many concomitant medications. Retrospective studies have been conducted to determine the prevalence of DDIs. However, prospective studies on DDIs needing interventions in cancer patients have not yet been carried out. Therefore, a prospective study was designed to identify DDIs leading to interventions among ambulatory cancer patients receiving anticancer treatment. PATIENTS AND METHODS Patients starting with a new treatment regimen with i.v. or oral anticancer medication were asked to participate. The patients' medication was checked for DDIs by using drug interaction software. An expert team of clinical pharmacologists evaluated the relevance of these identified DDIs. If a DDI was qualified as potentially clinically relevant, an intervention was proposed to the treating (hemato)oncologist. Several variables were studied as determinants for performing an intervention. Descriptive statistics and uni- and multivariate logistic regression analyses were carried out. RESULTS In this study, 302 patients were included. A total of 603 DDIs were identified by the drug interaction software and judged by the expert team. Of all 603 DDIs, 120 DDIs were considered potentially clinically relevant. These 120 DDIs, present in a total of 81 patients, resulted in a clinical intervention already executed by the (hemato)oncologist in 39 patients (13%), while an additional intervention was proposed by a clinical pharmacologist in 42 patients (14%). The number of comorbidities and the number of 'over-the-counter' drugs were identified as determinants. CONCLUSIONS Clinical interventions on DDIs are frequently required among patients starting with anticancer therapy. Structured screening for these potentially clinically relevant DDIs, by (hemato)oncologists in close collaborations with clinical pharmacologists, should take place before the start and during anticancer treatment. CLINICAL TRIALS NUMBER This study was registered at the Dutch Trial Registry under number NTR3760.

[1]  J. Ebbesen,et al.  Fatal adverse drug events: the paradox of drug treatment , 2001, Journal of internal medicine.

[2]  R. Barrons,et al.  Evaluation of personal digital assistant software for drug interactions. , 2004, American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists.

[3]  J. Verweij,et al.  Complementary and alternative medicine during cancer treatment: beyond innocence. , 2006, The oncologist.

[4]  B. Stricker,et al.  Risk of falls after withdrawal of fall-risk-increasing drugs: a prospective cohort study. , 2007, British journal of clinical pharmacology.

[5]  Lisa Wang,et al.  Potential drug interactions and duplicate prescriptions among cancer patients. , 2007, Journal of the National Cancer Institute.

[6]  H. Guchelaar,et al.  Preventing adverse drug events in hospital practice: an overview , 2007, Pharmacoepidemiology and drug safety.

[7]  F. Chan,et al.  Guidelines for Prevention of NSAID-Related Ulcer Complications , 2009, The American Journal of Gastroenterology.

[8]  J. Bergerat,et al.  Potential pharmacokinetic interactions affecting antitumor drug disposition in cancer patients. , 2008, Anticancer research.

[9]  J. Hugtenburg,et al.  Potential drug interactions in cancer therapy: a prevalence study using an advanced screening method. , 2011, Annals of oncology : official journal of the European Society for Medical Oncology.

[10]  R. Mathijssen,et al.  Prevalence of potential drug–drug interactions in cancer patients treated with oral anticancer drugs , 2013, British Journal of Cancer.

[11]  R. Mathijssen,et al.  Drug-drug interactions with tyrosine-kinase inhibitors: a clinical perspective. , 2014, The Lancet. Oncology.

[12]  J. Verweij,et al.  Determining the optimal dose in the development of anticancer agents , 2014, Nature Reviews Clinical Oncology.