Classification and occurrence of clinically significant drug interactions with irinotecan and oxaliplatin in patients with metastatic colorectal cancer

Background: Pharmacokinetic and pharmacodynamic drug interactions with cytotoxic drugs may significantly influence the efficacy and toxicity of chemotherapy. Objective: 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. Methods: 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. Results: 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). Conclusions: 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. Copyright (c) 2005 Excerpta Medica, Inc

The Development of Practice Recommendations for Drug-Disease Interactions by Literature Review and Expert Opinion

Background Drug-disease interactions negatively affect the benefit/risk ratio of drugs for specific populations. In these conditions drugs should be avoided, adjusted, or accompanied by extra monitoring. The motivation for many drug-disease interactions in the Summary of Product Characteristics (SmPC) is sometimes insufficiently supported by (accessible) evidence. As a consequence the translation of SmPC to clinical practice may lead to non-specific recommendations. For the translation of this information to the real world, it is necessary to evaluate the available knowledge about drug-disease interactions, and to formulate specific recommendations for prescribers and pharmacists. The aim of this paper is to describe a standardized method how to develop practice recommendations for drug-disease interactions by literature review and expert opinion. Methods The development of recommendations for drug-disease interactions will follow a six-step plan involving a multidisciplinary expert panel (1). The scope of the drug-disease interaction will be specified by defining the disease and by describing relevant effects of this drug-disease interaction. Drugs possibly involved in this drug-disease interaction are selected by checking the official product information, literature, and expert opinion (2). Evidence will be collected from the official product information, guidelines, handbooks, and primary literature (3). Study characteristics and outcomes will be evaluated and presented in standardized reports, including preliminary conclusions on the clinical relevance and practice recommendations (4). The multidisciplinary expert panel will discuss the reports and will either adopt or adjust the conclusions (5). Practice recommendations will be integrated in clinical decision support systems and published (6). The results of the evaluated drug-disease interactions will remain up-to-date by screening new risk information, periodic literature review, and (re)assessments initiated by health care providers. Actionable Recommendations The practice recommendations will result in advices for specific DDSI. The content and considerations of these DDSIs will be published and implemented in all Clinical Decision Support Systems in the Netherlands. Discussion The recommendations result in professional guidance in the context of individual patient care. The professional will be supported in the decision making in concerning pharmacotherapy for the treatment of a medical problem, and the clinical risks of the proposed medication in combination with specific diseases