Whether hygroscopic medicines can be stored in one-dose packages is often judged by information based on the quality evaluations of nonpackaged medicines. We previously reported that moisture absorption of nonpackaged hygroscopic medicines absorbed more moisture than did those stored in one-dose packages. In addition, when more than one of the same or different types of hygroscopic medicines were stored together in one-dose packages, the amount of moisture absorbed by each medicine is lower than that absorbed by medicine stored separately in one-dose packages. Moisture absorption of hygroscopic medicines usually depends on the humidity of the preservation environment. In this study, we measured the humidity change inside one-dose packages of cellophane polyethylene laminating paper included with magnesium oxide tablets, which are hygroscopic medicines, under 75％ relative humidity and 25℃. The humidity inside one-dose packages declined when magnesium oxide tablets were stored inside the packages. That effect was strongly dependent on the number of magnesium oxide tablets in the one-dose packages. Therefore, the moisture absorption of Glucobay^® and Glucobay^® OD tablets stored in one-dose packages was reduced when the tablets were stored with magnesium oxide tablets. This inhibitory effect also correlated with the quantity of magnesium oxide. In conclusion, the humidity inside one-dose packages containing hygroscopic medicines such as magnesium oxide tablets was lower than the humidity inside one-dose packages that did not contain hygroscopic medicines; thus, hygroscopic medicines may help preserve the quality of other hygroscopic medicines when packaged together inside one-dose packages.

Given that the cancer gene panel test was approved in June 2019, precision medicine based on the information about somatic mutation is expected to be widely available. Similarly, pharmacogenomics (PGx) associated with germline genes, such as drug-metabolizing enzymes, could also be effective tools. However, its clinical implementation has been delayed.

To address this issue, we conducted a survey regarding pharmacists’ involvement in “cancer genomic medicine (CGM)” and actual use of PGx and therapeutic drug monitoring (TDM). The response rate of the survey was 96.8％ (121/125).

According to this survey, genetic polymorphism analysis for irinotecan (UGT1A1), which is approved for genetic testing, was most commonly used. Among the tests not covered by insurance, tacrolimus (CYP3A5) and voriconazole (CYP2C19) were commonly used. Only a few facilities conducted PGx tests. Unlike PGx, many drugs are covered by insurance for TDM, which was commonly used. Vancomycin was most commonly used, followed by teicoplanin and cyclosporine. Regarding CGM, it was found that the pharmacists were most commonly involved in dose adjustment support, followed by support for selection of anti-cancer agents. Pharmacists’ participation in the expert panel was 21.3％.

This survey revealed that PGx testing is less common compared with TDM. PGx of drug-metabolizing enzymes could potentially influence adverse reactions and efficacy. It might be possible to provide individualized pharmacotherapy if PGx testing could be performed at the same time as gene panel tests. Insurance-covered PGx testing may increase in the future if more high-quality clinical trials are conducted and its usefulness is validated.

We report the case of a 19-year-old woman with severe idiopathic pulmonary arterial hypertension who had been treated with upfront triple combination therapy comprising macitentan, tadalafil, and intravenous epoprostenol (EPO). One and a half years after the initiation of combination therapy, when EPO was increased to 18.87 ng/kg/min, mean pulmonary arterial pressure (mPAP) and cardiac index (CI) significantly improved from 40 to 19 mmHg and from 4.11 to 2.43 L/min/m², respectively. After normalization of pulmonary hemodynamics, we decided to switch the prostacyclin pathway drug from EPO to oral selexipag. When selexipag was increased to 800 μg/day, she presented with significant nausea and headache. After simultaneous administration of metoclopramide (5 mg) and acetaminophen (200 mg) as estimated by maximum blood concentration of an active metabolite of selexipag, she could finally tolerate 3,200 µg/day selexipag. EPO was tapered off after careful observation for potential clinical worsening. Eight months after weaning from EPO, her pulmonary hemodynamics remained within the near-normal range as evidenced by mPAP (21 mmHg) and CI (4.45 L/min/m²), indicating the short-term success of switching from EPO to selexipag. In conclusion, effective management of side effects by pharmacists according to the pharmacokinetics of selexipag and its metabolites resulted in restoring the side effects, enabling us to increase selexipag to its maximum dosage. Consequently, EPO was successfully switched to oral selexipag with improved activity in daily life. There have been no reports on the transition from EPO to selexipag, and we report the first case.

Reuse of unused syringes returned to the Department of Pharmacy requires sufficient amounts of labor because of several factors including syringe names to be checked and it is also associated with the risk of oversight resulting from visual inspection. To improve operational efficiency and safety, the automatic restocking and dispensing machine(restocker) was incorporated into the automatic syringe dispensing machine (picker) as a trial. The picker enables sorting of returned syringes, confirmation of expiration dates, and dispensing of syringes according to the prescription. Both syringes stocked and unstocked in the picker's cassette are subject to the dispensing. The time required for the returned syringe handling was significantly reduced from the previous 8.86 ± 2.51 to 1.10 ± 0.39 seconds after the introduction of the restocker (P < 0.01). Regarding accuracy, no sorting error was found after sorting of 10,275 syringes. Between June and September, 2015, a total of 19,522 syringes were dispensed according to the prescription, of which 1,841 (9.43％) were picker-unstocked syringes. The stocker that directly dispenses injections cut 26.89 ± 6.65 seconds, the time required for the dispensing by hand. An additional 24 picker-unstocked items were dispensed between September and November 2018, as compared with the number in 2015. The restocker also acts like a virtual cassette as it can flexibly and automatically dispense picker-unstocked syringes while reflecting syringe availability in the hospital and seasonal changes. Based on the above, multiple functions of the restocker are useful for more efficient and safe returning and dispensing of syringes.

We proposed an in vitro test based on pH changes in ophthalmic solutions with the addition of lacrimal buffer, and examined anti-allergic ophthalmic solutions (acitazanolast hydrate, amlexanox, epinastine hydrochloride, ketotifen fumarate, levocabastine hydrochloride, olopatadine hydrochloride, pemirolast potassium, sodium cromoglycate, and tranilast) and anti-glaucoma ophthalmic solutions (brimonidine tartrate, carteolol hydrochloride, dorzolamide hydrochloride, isopropyl unoprostone, pilocarpine hydrochloride, timolol maleate, and travoprost) by using the in vitro test. Resistance to the lacrimal buffer capacity of ketotifen ophthalmic solution was higher than that of the other anti-allergic ophthalmic solutions tested. Among anti-glaucoma ophthalmic solutions, resistance to the lacrimal buffer capacity of the isopropyl unoprostone and dorzolamide ophthalmic solutions was higher than that of the other ophthalmic solutions tested. We also found relationships between ophthalmic additives and the pH-buffering effect in ophthalmic solutions, and demonstrated that D-mannitol, which is an ophthalmic additive, resisted the pH-buffering effect in artificial tears. Furthermore, high resistance was observed to the lacrimal buffer capacities of ophthalmic solutions with D-mannitol. These results will contribute to further studies aimed at reducing irritation caused by ophthalmic solutions.

Precipitation is one of the most serious incompatibilities of injections. To avoid drug precipitation in the clinical setting, pharmaceutical industries provide the physical compatibility data of their own products. However, these data were mainly obtained under a still standing condition, and therefore the effects of physical stress by infusion pump or of difference in the content of additives are largely unknown. To elucidate these problems, two different products of etoposide injection were subjected to the compatibility testing. After dilution by normal saline or 5％ glucose solution to give a final concentration of 0.2-1.0 mg/mL, diluted injections were pumped through a mid-press type peristaltic pump for 28 hours. Then, diluted injections before and after pumping (corresponding to without and with physical stress, respectively) were sampled over time. Compatibility was evaluated by the grading of insoluble particles by visual inspection, and the latest sampling time without visible insoluble particles was defined as the longest available time. In addition, the number of insoluble particles was counted using a particle counter. The longest available time was shortened by the increase of etoposide concentration, and was shorter when diluted with normal saline. In addition, the longest available time was shortened by pumping, and the magnitude of change was notably different between the two products, indicating that the additives contributed to the physical compatibility to some extent. Furthermore, the number of insoluble particles increased with the increase of the visual grading, indicating that the particle counter provides the objective criteria for the compatibility testing of injections in the clinical setting.

Esflurbiprofen (SFP) mentha oil formulation (SFP tape) is a tape-type patch containing a non-steroidal anti-inflammatory drug (NSAID) SFP, as the active ingredient. In clinical practice, there is a perception that SFP tape is not always easy to remove from the applied site. In this study, we evaluated the adhesive performance, tack and peel strengths of a formulation modified SFP tape prepared with the aim of reducing peel strength to improve the “difficulty of removal” after application. Prior to evaluation, bioequivalence between the modified SFP tape and the commercial SFP tape was verified. In vitro drug release-rate and skin permeation profiles of both formulations were shown to be comparable, as were the drug plasma concentration-time profiles in hairless rats after application. Tack and peel strengths were evaluated using the ball tack and 180° peel tests, respectively. Our results demonstrated that the formulation modified SFP tape while retaining tack strength (difficult to pull apart on application) reduced peel strength when compared with the commercial SFP tape. Furthermore, peel strength was determined to be comparable to representative marketed NSAID tape-type patches. In conclusion, the formulation modified SFP tape with demonstrated bioequivalence to the commercial SFP tape showed improved “difficulty of removal” after application while retaining sufficient tack strength.