We previously reported that tolvaptan may influence warfarin pharmacodynamics in vivo; however, the mechanism responsible for this influence was not clear. In this study, we investigated the drug-drug interactions between warfarin and tolvaptan by measuring warfarin blood concentrations in 18 patients who received warfarin therapy and in 24 who received warfarin + tolvaptan therapy. The free warfarin concentrations significantly increased in patients who were also receiving oral tolvaptan (p = 0.04). In vitro albumin-binding experiments showed that the free warfarin concentrations significantly increased with the addition of tolvaptan, in a dose-dependent manner, through albumin-binding substitution (approximately 2.5 times). Both clinical and in vitro data showed that tolvaptan increased the unbound warfarin serum concentration. The prothrombin time-international normalized ratio (PT-INR) tended to increase within 2 weeks when tolvaptan was added at clinically used doses (p = 0.14). Special attention is warranted in cases with a serum tolvaptan concentration of ≥ 125 ng/mL (≥7.5 mg/day) for at least 2 weeks following oral tolvaptan administration.
Care workers at care facilities play an important role in providing medication-administration assistance, and in medication risk management. Nevertheless, research has not made clear the specific concerns that care workers have at work sites, as well as the extent of their burdens. Thus, we conducted a questionnaire survey from October 1 through October 31, 2014 for staff who provide medication-administration assistance at for-pay elderly person homes about the concrete concerns and burdens with regards to the assistance. A total of 1,677 respondents were analyzed: 228 nurses and 1,449 care workers. Results showed that the care workers had a variety of problems and issues. These included the fact that, since care workers are not medical profession, they were unable to answer questions that the facility residents asked about their medications; they had concerns regarding their own lack of awareness of the efficacies of medications, and as to whether certain drugs were inappropriate for certain patients with swallowing dysfunctions; they wondered whether drugs in tablet forms had to be crushed before administration. They also encountered pharmacological-related issues, including whether administration times and numbers failed to match the lifestyle patterns of facility residents, and so forth. It is presumed that, with active intervention of pharmacists within facilities, these issues could be resolved. Study results, thus, suggested the need for system creation whereby pharmacists can become deeply involved in medication-administration assistance along with the care workers within facilities.