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Management of warfarin drug interactions is often complicated by lack of information regarding interactions with new drugs and with herbal medicinals. The pharmaceutical industry has increased both the number and quality of drug interaction studies prior to marketing new agents. Interactions may still occur in patients, however, despite negative pre-marketing studies in healthy volunteers. The clinical significance and intensity of warfarin interactions with prescription drugs (e.g., celecoxib, proton pump inhibitors, and selective serotonin reuptake inhibitors) can often be predicted on the basis of known metabolic characteristics of the drugs and warfarin enantiomers. Drug interactions with herbal medicinals are much more difficult to characterize and predict because of the lack of federal regulations regarding safety, efficacy, and manufacturing standards. Published case reports of interactions between warfarin and even the most widely used herbal medicinals are limited. Practitioners are encouraged to report such interactions through the FDA MedWatch program.