The objective of this study was to evaluate the cost-effectiveness of pegfilgrastim (Peg-G) and daily filgrastim (Fil-G) for the primary prophylaxis against febrile neutropenia (FN) in patients with non-Hodgkin lymphoma (NHL) who received cyclophosphamide, vincristine, doxorubicin and prednisolone (CHOP) therapy. We developed a decision analytical model reflecting the clinical processes of NHL patients who received first CHOP therapy. The probabilities at each clinical endpoint were obtained from published sources. To estimate the costs and duration of FN treatment, we analyzed the medical records of NHL patients in hospitals participating in this study. The costs of Peg-G and Fil-G were calculated according to the National Health Insurance drug price list. We assessed an incremental cost-effectiveness ratio (ICER) for a single dose of Peg-G versus 11-days of Fil-G from the perspective of health insurance payers. The sensitivity and robustness of this model were validated by the tornado-diagram and Monte Carlo Method. The costs associated with primary prophylaxis with a single dose of Peg-G and 11-days of Fil-G were 109,628 JPY and 109,243 JPY, respectively. The quality adjusted life years (QALYs) associated with the two strategies were 0.0339 QALYs and 0.0337 QALYs, respectively. The ICER for the Peg-G versus Fil-G was 2,788,571 JPY per QALY. The tornado-diagram revealed that the main influential factors included the cost of Peg-G, number of Fil-G doses, and cost of Fil-G. Monte Carlo simulation revealed an 18.3％ probability that Peg-G was cost-effective compared with Fil-G. A single dose of Peg-G was cost-effective compared with 11-days of Fil-G.
We studied safety in terms of the drug storage-requirement, preparation procedure and use of closed system transfer devices (CSTD) for reusing the residual drug solution in a single-dose vial, which was based on the presupposition that cleaning with ethanol was performed before reuse. Bacillus subtilis was applied to a rubber stopper on a simulated vial or to three types of CSTD connected to the vial and allowed to stand for 24 or 48 hours. After 6 times of wiping, punctured with 18G needle or CSTD. As a result of culturing, bacteria were detected in all groups.
Therefore, Bacillus subtilis was separately applied to a rubber stopper of the same simulated vial separately, and after wiping, bacteria remaining on the rubber stopper were cultured and counted. Contamination was detected in about 1/10 of the coating amount. It is suggested that complete removal of bacteria, which is expected to have a disinfection effect, is difficult by wiping alone and microorganisms adhering to the rubber stopper may contaminate the vial at the time of puncture. It was confirmed that when reusing the residual drug solution in a single-dose vial, microbial contamination into the vial can occur if the puncture site of the vial is not kept clean, regardless of whether or not CSTD is used. In the case of storing in an environment where microbial contamination can occur, it is necessary to consider a method by which bacteria can be completely removed.
A combination chemotherapy regimen comprising oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX) is an approved treatment for unresectable pancreatic cancer and has a high therapeutic effect; however, it also has many side effects. One such undesirable side effect is dysarthria, which is believed to be caused due to the inhibition of cholinesterase by irinotecan. This study evaluates the prophylactic efficacy of scopolamine butylbromide for FOLFIRINOX-induced dysarthria. All patients who were administered FOLFIRINOX between March 1, 2014 and January 31, 2018 at the Japanese Red Cross Kyoto Daini Hospital were enrolled. Dysarthria developed in 9 (50％) out of 18 patients; these patients exhibited a high rate of apply to risk factors defined by the Japanese Society of Pancreatic Cancer (P = 0.018). Patients with dysarthria were given an oral dose of scopolamine butylbromide. None of the patients in whom scopolamine butylbromide was prophylactically administered experienced dysarthria in any of the treatment cycles; furthermore, no adverse events associated with scopolamine butylbromide use were observed in these patients. Our results show that scopolamine butylbromide may represent an option as a prophylactic agent for patients with FOLFIRINOX-induced dysarthria.
Tablet splitting, an important task of the pharmacist, is performed at hospitals and health insurance pharmacies. Although magnesium oxide tablets have no score line, the accuracy of their division is not assured. Furthermore, as magnesium oxide strongly absorbs moisture, the stability of half-tablets is unknown when stored in one-dose packages. The variation and loss when splitting magnesium oxide 500 mg tablets by using a tablet-divider were evaluated. The stabilities of split tablets after storage in one-dose packages at 75％RH were evaluated through the analysis of weight change, disintegration, and dissolution. The variation in half-tablets of magnesium oxide 500 mg tablets was 5.5 ± 4.4％ and the loss of almost all tablets was below 1％. Although the weight of the half-tablets increased when preserved in one-dose packages, this was related to the quantity of magnesium oxide stored in one-dose packages and not on the splitting of tablets. The disintegration time of half-tablets was prolonged by increased moisture absorption, but the disintegration time of split tablets was shorter than that of whole tablets when the same quantity of moisture was absorbed. The dissolution rate was similar among split tablets and whole tablets. Magnesium oxide tablets can be administrated as a split tablet, but caution should be exercised regarding prolonged disintegration time. Pharmacists should be careful when using half-tablets in prescriptions.
As part of standardizing the prescription format of oral drugs, the Ministry of Health, Labour and Welfare has stipulated that the amounts of oral drugs in prescriptions should be described as “amounts-per-dose” and not as “amounts-per-day.” However, because of the sense of resistance among physicians arising from concerns of increases in medical accidents and work volume, the transition from “amounts-per-day” prescription to “amounts-per-dose” prescription has not been implemented in most facilities. We conducted a survey to investigate the attitudes of physicians in our hospital toward the “amounts-per-dose” prescription and changes in their attitudes by the provision of appropriate information to them. The same questionnaire consisting of 15 items reflecting the “amounts-per-dose” prescription was conducted before and after the presentation of references related to the “amounts-per-dose” prescription to the physicians. The survey results were analyzed by two-way repeated measures analysis of variance using “clinical departments” and “presentation of references” as factors. No interactions were observed. Only two items in the “clinical departments” factor showed significant differences in the main effects, whereas six items in the “presentation of references” factor showed significant differences in the main effects. All of these items showed positive changes after the presentation of references. These results demonstrated that physicians' sense of resistance to the “amounts-per-dose” prescription was derived from a lack of appropriate information and that their sense of resistance was alleviated after being appropriately informed.