This review describes the clinical outcomes of pharmaceutical interventions and bidirectional sharing of patient information between a hospital and community pharmacies in outpatient chemotherapy. First, we retrospectively evaluated the clinical outcomes of 56 pharmaceutical interventions relating to chemotherapy-induced adverse events and estimated their associated economic impact. Twenty-nine of the pharmaceutical interventions significantly decreased the grade of adverse events compared with before pharmaceutical interventions. The number of reductions in grade 1, 2, and 3 was 14, 11, and 4, respectively. In accordance with the potential economic costs associated with the Adverse Drug Reaction Relief System of the Pharmaceuticals and Medical Devices Agency and reduction of grade, we estimated that the total cost saving associated with the clinical outcomes of pharmaceutical interventions was JPY11,360,000. Second, we developed a system for bidirectional sharing of patient information between a hospital and community pharmacies, which comprised a modified prescription format and a monitoring sheet for tegafur/gimeracil/oteracil potassium (S-1). Questionnaire surveys showed that community pharmacies significantly understood patient information compared with before the sharing system. We also retrospectively investigated the discovery rate of adverse events in outpatients who had received S-1. The proportion of patients who developed all grades of an eye symptom and grade ≥ 2 nausea significantly increased after implementation of the sharing system, showing that the system was able to track adverse events. In addition, the proportion of patients in which clinicians managed the adverse events slightly increased. These results suggest that our interventions contribute to the quality and safety of outpatient chemotherapy.
One-dose packages are useful for managing complicated medication regimens for older patients. We experienced a case of Bayaspirin® tablet 100 mg (BA) and Micardis® tablet 40 mg (Mic 40) that were fused in a one-dose package at the time of medicine reconciliation. To our knowledge, there are no previous reports assessing the quality of these tablets caused by this physical incompatibility. Therefore, we aimed to examine this phenomenon and its impact on the drug compositions, as well as to identify the mechanisms.
BA and Mic 40 in one-dose packages were stored at 30℃/75％ relative humidity (RH) or 93％RH condition for 1 week. The stability evaluations were performed on appearance change, hardness, content, and dissolution rate. The active ingredients in each tablet were investigated to determine the mechanisms.
Mic 40 showed changes in appearance and hardness, while BA showed a changed appearance, and reduced content and dissolution rate. The enteric coatings of BA and the additive in Mic 40 had an influence on the mechanism of incompatibility.
Mic 40 contains meglumine, which is hygroscopic and deliquescent. Therefore, meglumine absorbs moisture and becomes a basic solution. Methacrylic acid copolymer LD dissolved in this basic solution results in adhesion with Mic 40 and leads to a decrease in both the content and the dissolution rate in BA. This is the first study to analyze the physical incompatibilities of enteric-coated aspirin tablets with non-coated telmisartan tablets in one-dose packages and provides useful information for clinical practice.
Enoxaparin sodium (EXP) is useful in preventing the development of venous thromboembolism (VTE) after abdominal surgery. In a phase III clinical study (EXP-P3-study), EXP was administered for 14 days after surgery; however, the dosing period recommendations in Japan remain unclear. In our hospital, EXP was administered for a period of 5 days, and the efficacy and safety of this treatment were retrospectively surveyed to assess whether short-term administration of EXP was useful in patients.
The subjects included 152 patients who were administered EXP after abdominal surgery. The mean dosing duration of EXP was 4.3 ± 1.1 days. Among the subjects, one patient developed VTE, and 3 developed a major hemorrhage (2.0％). The efficacy rate of EXP in preventing VTE was 99.3％.
In the EXP-P3-study, the incidences of VTE in patients administered or not administered EXP were 1.2％ and 19.4％, respectively. In the cohort of the present study, the incidence of VTE was markedly controlled as compared to that in patients who were not administered EXP. The major hemorrhage rates of the EXP-administered group and non-EXP-administered group were 4.6％ and 2.6％, respectively, in the EXP-P3-study. In the current study, the major hemorrhage rate was similar to that of the non-EXP-administered group in the EXP-P3-study.
In conclusion, the present study suggests that administration of EXP for 5 days was not less effective compared with administration for 14 days. Therefore, it is suggested that 5-day administration of EXP was useful in preventing the development of VTE after abdominal surgery.
There are few reports regarding the optimal decomposition condition of the antimicrobial agent. We therefore conducted a questionnaire about the decomposition operation of the antimicrobial agent vial preparation for nurses in Osaka Saiseikai Nakatsu Hospital. Furthermore, the optimal dissolution conditions for “Zosyn ® IV for intravenous injection 4.5 (tazobactam/piperacillin; TAZ/PIPC)” were examined. As a result of the questionnaire survey, most nurses selected a syringe of 10 mL for formulations that are easy to dissolve while, for difficult to dissolve formulations, answers were split between 10 mL and 20 mL. The shaking time of vials ranged from under 5 seconds to under 30 seconds for the soluble formulations and from under 5 seconds to more than 1 minute for the difficult to dissolve formulations. We set each decomposition condition from the questionnaire results and examined the optimal condition, which accorded with the clinical settings in the decomposition operation of TAZ/PIPC. As a result of having examined the decomposition condition from the absorbance of each complete decomposition preparation of TAZ/PIPC, it was found that more than 93％ of dissolution was carried out with the injection of saline at 15 mL and the shaking time of 10 or 20 seconds, or the injection of saline at 20 mL and the shaking time of 10 seconds. If the injection volume and the shaking time are less than these conditions, residual drugs are found in the vials.
Osimertinib is an irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) that is selective for both EGFR-TKI sensitizing and T790M resistance mutations. Because the application for drug approval was filed in Japan in 2016, few studies analyzing its adverse drug reactions in clinical practice have been reported. In this study, we aimed to evaluate the characteristics of osimertinib by comparing the onset of adverse drug reactions between Kyushu University Hospital (n = 16) and a clinical trial (Japanese subjects in AURA study phase II and AURA2 study: AURA study, n = 80). We found that the rates of decrease in neutrophil and platelet counts were significantly higher in the Kyushu University Hospital study than in the AURA study. At Kyushu University Hospital, a decrease in neutrophil count tended to be reported shortly after the start of treatment, and a decrease in platelet count was expressed over time. It became clear that osimertinib has little effect on hepatic dysfunctions, especially during the early stage of treatment. Consequently, when evaluating adverse drug reactions, it is important to perform a comprehensive analysis that includes aggravation of adverse drug reactions and variations of laboratory data from baseline. We believe that the additional information obtained from our study will lead to improvements in adverse drug reaction monitoring and patient education.
Some powder formulations of anticancer drugs are currently distributed under negative pressure in vials. However, the internal pressures of the vials are not described in the package inserts. Therefore, an awareness survey was conducted involving pharmacists regarding their descriptions.
Anonymous questionnaires, consisting of a 5-grade scale and free description questions, were distributed to the member hospitals of Hyogo Pharmaceutical Society, and responses were collected by FAX and 2-top ratio analysis was performed. In addition, an intergroup comparison was conducted by dividing the responders into two groups based on their experiences (i.e., more or less than 3 years) of dispensing anticancer drugs.
Responses were collected from 246 pharmacists of 67 hospitals: “Need prior information” (82.5％) and “Need description” (79.3％). Among the pharmacists with experience of less than 3 years, “Feel anxiety,” “Need prior information,” and “Feel safe with description” were more common (P < 0.05). Of them, 79.3％ specified description sites: vial body (90.8％), cap (65.1％), and package insert (39.5％). Internal pressures were listed on a sheet or described in the procedure manual in only 13 hospitals, demonstrating dependence on dispensers' experiences. Besides the internal pressure, they needed information on the recommended gauge, amount of dissolution, and kind of solvent on the vial bodies.
We investigated the current situation of pharmacists' recognition of and countermeasures they take against adverse drug reactions (ADRs) in order to elucidate related factors. We administered a web-based questionnaire to pharmacists who work at community pharmacies. The factors included in the questionnaire were basic information, recognition of and countermeasures against ADRs (the frequency of ADR recognition, investigation medium, the recognition of and countermeasures against ADRs and reasons for those). There were 29 questions about ADR education in total. In this study, we focused on the frequency of ADR recognition and countermeasures taken against ADRs, and examined their current status and related factors. As a result, after performing multivariable logistic regression analysis, we found that the group of pharmacists who made prescription inquiries about patients had an association with the investigation medium they used and are likely to investigate actively. Our results suggest the possibility that many pharmacists differed in their knowledge about the onset and recognition of ADRs. Moreover, our results found situations where prescription inquiries were actively made, but ADRs were not adequately reported. In conclusion, pharmacists who make prescription inquiries are likely to investigate and actively use information media, and this suggests the necessity of selecting the appropriate information medium and critically examining information. However, since those who answered our survey were biased towards the young, it is necessary to consider the possibility that this influenced the results.
The characteristics of eye drop (ophthalmic solution) containers are reported to be associated with the appropriate use of eye drops. Since patients complain that AZORGA® Combination Ophthalmic Suspension (AZORGA® hereafter) requires more push-out force than other eye drops, there is a possibility that the container of AZORGA® is less usable than other commercially available eye drop containers in Japan. Therefore, we compared the Alconpharma container used for AZORGA® and 3 representative containers as controls, which are available in large quantities in Japan. In addition, a subjective usability questionnaire was performed in healthy adults, and the influences of containers on the subjective usability of high-viscosity eye drop suspensions, such as AZORGA®, were evaluated.
The Alconpharma container showed a significantly higher squeeze force necessary to push out 1 drop of AZORGA® and a slightly higher variability in the squeeze force among instillations than that in the other 3 containers. In association with these characteristics of the containers, the subjective usability scores for “container's hardness during instillation” and “easiness of pushing 1 drop out” were significantly lower for the Alconpharma container than for the other 3 containers. These results suggest that not only the characteristics of the AZORGA® solution (high viscosity and suspension) but also those of its container affect the subjective usability of eye drop products.