Background: Teriflunomide (TER) and dimethyl fumarate (DMF) have been approved as first-line oral treatments for relapsing-remitting multiple sclerosis (RRMS) in the United States and Europe. Therapeutic positioning of TER in RRMS management have not been fully established. Therefore, this study was aimed at directly comparing the efficacy and safety of these two drugs for treating RRMS by conducting a meta-analysis. Methods: We searched MEDLINE, the Cochrane Library, and Igaku Chuo Zasshi databases for articles included until December 2020. The inclusion criterion was a clinical study comparing the efficacy and safety of TER and DMF in patients with RRMS. Results: Among 263 relevant articles, 16 cohort studies were found eligible for inclusion in the meta-analysis. There were no significant differences between TER and DMF in total relapses (odds ratio, OR: 1.15 [95% confidence interval, 95% CI: 0.94-1.40]), Expanded Disability Status Scale progression (OR: 1.38 [95% CI: 0.80-2.39]), MRI activity (OR: 1.09 [95% CI: 0.63-1.88]), incidence of adverse events (OR: 0.83 [95% CI: 0.44-1.55]), and treatment discontinuation due to adverse events (OR: 0.90 [95% CI: 0.73-1.12]). The TER-associated rate of treatment discontinuation due to inefficacy (OR: 2.17 [95% CI: 1.85-2.53]) was significantly higher than that associated with DMF. Conclusions: TER was as effective and safe as DMF, except for the rate of treatment discontinuation due to inefficacy. Thus, TER could be a treatment option for RRMS in Japan.

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Controlling blood glucose levels is important to prevent the occurrence of type 2 diabetes complications. Recently, GLP-1 receptor agonists have been recommended in major guidelines for the treatment of diabetes. Several studies on GLP-1 receptor agonists have been conducted; these drugs are expected to exhibit not only an improvement in blood glucose levels but also in lipid levels, as well as abnormal liver and kidney function tests. GLP-1 receptor agonists are administered as once-weekly long-acting or daily short-acting preparations. Although better medication adherence has been reported with the once-weekly administration, there has been no report on the comparison of their therapeutic outcomes. Therefore, we performed a comparative analysis of changes in biochemical parameters following once-weekly dulaglutide (the most prescribed GLP-1 receptor agonist) and daily liraglutide. In this retrospective study, values of eight parameters (HbA1c, LDL-C, HDL-C, triglycerides, AST, ALT, γ-GTP, and eGFR) were extracted from medical records, and differences in these values at the initiation of administration and 6 months after the initiation were assessed. The results showed a significant decrease in HbA1c at 6 months in both dulaglutide and liraglutide groups. There was also a significant decrease in triglycerides in the dulaglutide group. Thus, dulaglutide and liraglutide are both effective at controlling blood glucose levels, although dulaglutide also improves lipid levels. These findings suggest that the once-weekly administration is more useful for diabetes treatment than the daily administration.

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HbA1c is widely used as an efficacy index in the treatment of diabetes, and HbA1c level before administration of hypoglycemic agents, is considered one of the important predictors of hypoglycemic effect. In this study, we investigated the relationship between pre-administration HbA1c level and the HbA1c level 3 months after administration to determine the optimal interpolation method when using the HbA1c level 6 months before administration in diabetic patients treated with DPP-4 inhibitors as monotherapy. With 221 enrolled patients, the post-administration HbA1c level that showed the best correlation with the pre-administration HbA1c level was the measured real value (correlation coefficient: 0.59). It is higher than the difference and the rate of HbA1c levels before and after administration. Comparing the correlation with HbA1c level after administration using various pre-administration HbA1c levels indicates that the correlation coefficient was higher when the HbA1c level 6 months before administration was used than when one point of the pre-administration value was used. The highest correlation (correlation coefficient: 0.62) was shown by the backward interpolation method. HbA1c is known to have intra-individual variation. It is considered that higher correlation with HbA1c after administration was obtained when the HbA1c level was used multiple times in the 6 months before administration because the intra-individual variations could be absorbed. Among various interpolation methods, the backward interpolation method showed the highest correlation, which is consistent with HbA1c being an indicator of blood glucose status in the past 1-2 months. This study is an exploratory study in which pre-administration HbA1c level of DPP-4 inhibitors was univariately analyzed. Univariate analysis of pre-administration HbA1c level in patients treated with DPP-4 inhibitors was conducted. It was shown that a method of retrospectively interpolating HbA1c level for 6 months before administration may be useful as a predictor of hypoglycemic effect.

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Usually, drug tablets are dispensed without splitting. However, in clinical practice, tablets are sometimes split for patients who need to adjust their dosage or when the prescribed dose tablet is not available at the hospital or pharmacy. In such cases, it is necessary to minimize the impact of tablet splitting on the loss of mass and drug elution behavior. Therefore, in this study, we aimed to provide a safer, and more reliable drug treatment, and thus, we examined the status of split dispensing the tablets of sitagliptin, a diabetes treatment drug with a high prescription frequency, in hospitals. We also examined the appropriate method for tablet splitting and evaluated its effects on the drug elution behavior at the time of splitting. Sitagliptin tablets were used in more than 90% of 34 surveyed facilities, and at least 80% of them used only the standard 50 mg tablet. At all facilities that used only 50 mg tablet, split tablets were dispensed only when 25 mg dose was prescribed. Therefore, comparison of tablets split using scissors to those using a spatula revealed that there was significantly less variation in the half-tablets split using scissors than in those using a spatula (p < 0.01). Additionally, comparison of the elution rates of 50 mg Januvia® half tablets to whole 25 mg Januvia® tablets revealed that the drug elution behaviors differed significantly. Therefore, even for tablets with a score line, such as Januvia® tablets, tablet splitting using scissors with little variation is an appropriate division method, and even at the same dose, the dissolution rate over time may differ between the ready-made products and split tablets, and therefore, it is an easy method. However, it was considered undesirable to dispense the medicine in split doses.

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Lacosamide (LCM) is an anticonvulsant drug that stabilizes hyperexcitable neuronal membranes by selectively promoting the slow inactivation of voltage-gated sodium channels. Therapeutic drug monitoring (TDM) is not commonly performed for LCM, because a therapeutic concentration range has not yet been established. We report a case of a 61-year-old man under treatment with 300 mg/day of LCM, who was rushed to the emergency room with epileptic seizure disorder. The patient developed paroxysmal atrial fibrillation and bradycardia-tachycardia syndrome during treatment. A pharmacist in charge of the ward analyzed his plasma LCM concentrations according to expected PK parameters. Since the incidence of adverse events increases with increasing plasma LCM concentrations, dosage for a patient with impaired renal function should be adjusted to compensate for the expected decrease in total clearance, or the predicted elevated plasma concentrations. Clinical trial results may be used as a reference for plasma concentrations. Performing TDM is recommended, since the knowledge of plasma concentrations of individual LCMs with confirmed efficacy and tolerability may be useful for dose adjustment during pharmacokinetic changes.

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Dabigatran, rivaroxaban, apixaban, and edoxaban are four direct oral anticoagulants (DOAC) that are currently used to treat patients with atrial fibrillation. However, no previous pharmacokinetic study has evaluated the estimated changes in unbound drug concentrations in the blood for these drugs. Here, we estimated the changes in unbound drug concentrations in the blood during organ dysfunction using the collected basic parameters of DOACs. Furthermore, the validity of the dosages described in the package inserts was assessed by taking into consideration the data on relationships between blood concentrations and effects of drugs (PK/PD). With respect to the elimination routes of the above four drugs, dabigatran was a renal excretion-type drug, rivaroxaban and edoxaban were of the intermediate type, and apixaban was a liver-metabolized drug. Organ clearance characteristics of the four drugs showed elimination dependency. Dabigatran and edoxaban were found to be binding-insensitive drugs, in which changes in total drug concentrations in the blood can be regarded as changes in unbound drug concentrations. In contrast, rivaroxaban and apixaban were binding-sensitive drugs, in which changes in total drug concentrations in the blood are not an indication of changes in unbound drug concentrations in the blood. In terms of organ dysfunction, the area under the curve (AUC) of dabigatran in patients with moderate renal dysfunction was 3.1-fold higher than that in healthy adults, suggesting that the dosage described in the package insert may be excessive. Meanwhile, the AUC of rivaroxaban in patients with moderate renal dysfunction was 1.19-fold higher than that in healthy individuals, whereas that of apixaban in patients with severe renal dysfunction was 1.42-fold higher, suggesting that the dosages described in the package inserts may be too low.

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Inoculation with a newly developed vaccine has started amid the spread of the new coronavirus disease (COVID-19). However, inoculating the entire population is difficult because of various issues such as limited personnel and time constraints. Under these circumstances, a faculty member of practical education at a pharmacy school with expertise in handling vaccines and preparation techniques consulted with the local pharmacist association. In collaboration with the association, a workshop which included lectures on the properties, preparation, dilution, and handling of the vaccine as well as dispensing of injection vials was held. The workshop was conducted mainly by university faculty members who were experts in academic education and research. Thus, pharmacists who participated in the workshop acquired knowledge and hands-on skills with peace of mind and could personally administer vaccines in groups. About 90% of the participants in the workshop diluted and dispensed the vaccine at the mass vaccination site. The workshop was considered meaningful because the faculty member was able to fulfill his duties at the venue.

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Magnesium oxide is contained in various non-prescription drugs; specifically, it is the main component of laxatives and is contained in absorption enhancers used for antipyretic analgesics. Important safety information is being collected as the use of magnesium oxide formulations has been associated with the risk of hypermagnesemia and mortality. In order to prevent severe adverse effects associated with hypermagnesemia following the use of non-prescription drugs that contain magnesium oxide, we aimed to establish evidence on important patient characteristics and indication for use of magnesium oxide formulations to help inform pharmacists and registered sellers. We examined the package inserts and identified that the maximum daily dose of magnesium oxide contained in laxatives and over-the-counter (OTC) drugs was approximately 2,000 mg, which is equivalent to the dose contained in prescription drugs. Furthermore, none of the drugs indicated specific dose considerations for kidney function in the package insert for patients. Analysis of the Japanese Adverse Drug Event Report (JADER) further demonstrated that the risk of mortality following the onset of hypermagnesemia was approximately twice as high in individuals over the age of 60 years. Additional meta-analysis demonstrated that the use of magnesium oxide was associated with elevated risk of hypermagnesemia in patients with kidney dysfunction (≥chronic kidney disease stage G3b) (RR (95% CI): 3.14 (1.56-7.45)). Collectively, these findings indicate that pharmacists and registered sellers need to understand the patient characteristics such as medication history, age, and kidney function when providing non-prescription drugs that contain magnesium oxide. Our findings also highlight the importance of providing information to patients about initial symptoms of hypermagnesemia and appropriate ways to deal with such symptoms.

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