Important Drug Interactions for Clinical Oncologists
Pp. 97-121 (25)
Hiroshi Ishiguro, Ikuko Yano and Masakazu Toi
Drug interactions can cause severe side effects and lead to early termination of drug development, refusal of drug approval, prescribing restrictions or drug withdrawal from the market. Of drugs used to treat humans, cytotoxic anti-neoplastic drugs have a particularly strong action. Furthermore, they have a complex pharmacological profile, a narrow therapeutic window, and a steep dose-toxicity curve, and are associated with considerable inter- and intrapatient pharmacokinetic and pharmacodynamic differences. The recommended dose is usually close to the maximally tolerated dose in order to achieve the maximum therapeutic effect. Thus, some adverse effects are usually inevitable, so these drugs are approved for usage based on a clinical risk to benefit ratio. Therefore, drug interactions affecting the pharmacokinetics of anti-neoplastic drugs are of particular concern. Any physicians treating oncology patients must understand the pharmacokinetic behavior (absorption, distribution, metabolism, excretion, etc.) of a drug, as well as the factors affecting its pharmacokinetic behavior, for example the effects of concomitantly administered drugs, and hepatic and renal function. Medical oncologists must have expertise in achieving a good balance between safety and efficacy in medical treatment, with a proper knowledge of supportive care and an understanding of pharmacokinetics, pharmacodynamics and pharmacogenomics. We summarize the drug interactions that are important in day-to-day oncology practice. We cover pharmaceutical interactions as well as the interactions at the levels of absorption, distribution, metabolism and excretion. This review is the one of the most comprehensive to date in the field of clinical oncology, where the level of understanding of drug interactions can directly affect patient management.
Department of Pharmacy and 3Breast Surgery Department, Kyoto University Hospital, 54 Shogoinkawaharara-cho,Sakyo-ku, Kyoto-city, 606-8507, Japan