Classification and occurrence of clinically significant drug interactions with irinotecan and oxaliplatin in patients with metastatic colorectal cancer
ABSTRACT Pharmacokinetic and pharmacodynamic drug interactions with cytotoxic drugs may significantly influence the efficacy and toxicity of chemotherapy.
The purpose of this study was to identify drug interactions with irinotecan and oxaliplatin reported in the literature, to assess their clinical significance, and to examine the occurrence of these interactions in patients with metastatic colorectal cancer treated with either irinotecan or oxaliplatin or both.
To obtain data on drug-drug interactions with irinotecan and oxaliplatin, a literature search of PubMed and EMBASE was conducted using the search terms irinotecan, oxaliplatin, and interactions (English-language studies only published between 1980 and August 2004). The interactions found were subsequently classified for documentation evidence and severity of clinical effect, according to a 5-level classification system of a standard reference text, by a study panel of medical oncologists and clinical pharmacists. Comedication of patients who were treated with irinotecan or oxaliplatin, or both, was then examined to determine the occurrence of clinically significant interactions.
Ninety-eight patients (50 women, 48 men;mean age, 60 years) were included in the study. Seventeen interactions with irinotecan were found in the literature, and 11 were classified as clinically significant. Only 1 nonspecific, clinically significant interaction was identified for oxaliplatin. Irinotecan-treated patients received a mean of 8 different comedications and oxaliplatin-treated patients received a mean of 6. Apart from antiemetic and antidiarrheal drugs that were prescribed for treatment-related toxicities, only 1 patient appeared to be exposed to a possible clinically significant interaction (between irinotecan and phenytoin).
Eleven of the 17 interactions with irinotecan that were found in the literature were classified as clinically significant versus 1 clinically significant interaction with oxaliplatin. The occurrence of these interactions in the study patients with metastatic colorectal cancer was low. For medication surveillance purposes, however, the significant interactions should be considered in clinical practice.
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ABSTRACT: The huge number of drug interactions makes it impossible to memorize them all. Detecting them and preventing adverse effects requires the use of reference works or databases. There are numerous discordances between the so-called "reference" books and databases. Nonexistent and unconfirmed interactions are published. The wording of the "drug interactions" section of the summary of product characteristics (SCP) sometimes sheds very little light on the risks involved. The delay by AFSSAPS in updating its drug interaction thesaurus may present problems in clinical practice. It is essential to know the limitations of the computerized systems for detecting and reporting drug interactions.La Presse Médicale 05/2008; 37(4 Pt 2):654-64. DOI:10.1016/j.lpm.2007.08.012 · 1.17 Impact Factor
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ABSTRACT: Drug-drug interactions (DDIs) comprise an important problem in medical oncology practice. We systematically reviewed the frequency of DDIs in oncology. We searched PubMed for eligible articles and on-line databases for abstracts of major oncology meetings. Eight studies reported on the frequency of DDIs: six evaluated the frequency of potential DDIs, while two studies reported on real DDIs, i.e. interactions that had clinical consequences. Studies of potential DDIs found that approximately one-third of patients are exposed to dangerous drug doublets, with the most common ones involving warfarin and anticonvulsants. One study of real DDIs found that 2% of hospitalized cancer patients had a DDI as the cause of admission. Drug interactions comprise an important issue in oncology, with approximately one-third of ambulatory cancer patients being at risk of DDIs. Data are limited on the clinical consequences of drug interactions among cancer patients.Annals of Oncology 09/2009; 20(12):1907-12. DOI:10.1093/annonc/mdp369 · 6.58 Impact Factor
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ABSTRACT: Anticancer drug interactions can affect the efficacy and toxicity of anticancer treatment and that of the interacting drugs. However, information on the significance, prevention, and management of these interactions is currently lacking. The purpose of this study was to assess the clinical significance of interaction among anticancer agents and comedications and to provide recommendations for the management of clinically significant interactions. Members of a multidisciplinary expert group of hospital and community pharmacists, medical oncologists, internists, and clinical pharmacologists were selected by their professional organizations, which participated in this consensus project. Literature was extensively searched for any drug interactions with anticancer agents using registration files, reference books, handbooks, and electronic databases. Interactions between anticancer agents were not considered. Interactions were classified by level of best available evidence for the interaction and by severity of the clinical effect, according to a structured assessment procedure. This assessment distinguished 5 levels for the amount and quality of evidence available and 6 severity levels for classification of potential drug-to-drug interactions. A total of 88 drug interactions with anticancer agents were identified from 146 combinations of drugs with anticancer agents found in literature. For 58 combinations, there was insufficient evidence of an interaction. Of the identified interactions, 38 were classified as clinically significant, defined as necessitating an alert or intervention, such as dose adaptation, comedication, discontinuation of treatment, or additional monitoring of treatment. Recommendations were made for management of these interactions. Numerous interactions with anticancer agents are clinically significant and should be considered by pharmacists and doctors in daily oncology practice.Clinical Therapeutics 04/2011; 33(3):305-14. DOI:10.1016/j.clinthera.2011.01.022 · 2.59 Impact Factor