Frequency and clinical outcome of potentially harmful drug metabolic interactions in patients hospitalized on internal and pulmonary medicine wards: Focus on warfarin and cisapride

Drug metabolic interactions present potential risks in patient care, but th eir frequency and relative importance as a clinical problem remains unclear . To assess the frequency and clinical outcome of potentially harmful drug metabolic interactions in hospitalized patients, the authors performed a su rvey of the medication data of patients treated on internal and pulmonary m edicine wards in a university hospital. The database was searched for conco mitantly administered drug pairs that would. according to Hansten and Horn' s drug interaction database, carry a high risk for a clinically harmful met abolic drug interaction. Coadministrations involving warfarin or cisapride were subjected to further analysis regarding clinical outcome. A total of 1 42 patients were exposed to 150 interactions with potentially harmful clini cal outcome, resulting in a frequency of 0.9% (95% CI 0.7% to 1.0%). Inhibi tion of warfarin metabolism by metronidazole produced significant overantic oagulation as evidenced by elevated international normalized ratio values, whereas inducers (rifampicin and phenobarbital) of warfarin metabolism sign ificantly reduced the efficacy of warfarin. One case of minor bleeding and one case of clavicular vein thrombosis were detected as possible consequenc es of disturbed anticoagulation. The coadministration of cisapride and eryt hromycin significantly prolonged the corrected QT (QTc) interval and was as sociated with clinical symptoms of cardiac arrhythmias. Coadministration of cisapride with fluconazole or miconazole was not associated with prolongat ion of the QTc interval or cardiac sequelae. Evaluations of patient materia ls are needed to assess the clinical relevance of metabolic drug interactio ns.