Multiple drug prescriptions can lead to poor adherence to the prescription, intensification of drug interactions and side effects, and an increase in medical costs. Recently, in Japan, polypharmacy has been considered problematic in connection with aging and the explosive growth of national medical expenses, and investigative research studies have been conducted for some diseases. We investigated the number of patients who had been prescribed six or more drugs in the palliative care unit over time and found that the number of patients who had been prescribed six or more oral and external medicines decreased over time. On the other hand, the decrease was slight when injection drugs were included. In addition, the number of multiple prescriptions of oral and external medicines decreased over time in patients who had been administered opioids prior to admission to the palliative care unit and those who died compared to the patients who had not been administered opioids and those who were discharged, respectively. In Japan, polypharmacy is a problem in drug-based treatment, which needs to be addressed. Therefore, we think that our results are a useful finding in the field of palliative care.

Nafamostat mesilate (NM) is used clinically for the prevention and treatment of pancreatitis. Electrolyte monitoring is necessary in geriatric patients receiving NM as it may cause hyperkalemia with the possibility of inducing arrhythmias. We attempted to evaluate the risk of hyperkalemia with aging and its background in this retrospective cohort study. Thirty-six of 290 patients (12.4％) who were receiving NM for the prevention and treatment of pancreatitis experienced hyperkalemia at the Kanazawa Medical Center over the past 2 years. A multiple logistic regression analysis was performed to identify the risk factors for hyperkalemia. The results showed that significant predictors of hyperkalemia were increasing age (per 10 years; odds ratio [OR]: 1.41, 95％ confidence interval [CI]: 1.01 - 1.96, P < 0.045), fever (OR: 3.11, 95％ CI: 1.25 - 7.71, P < 0.015), a high daily dose (per 10 mg/body/day; OR: 1.10, 95％ CI: 1.01 - 1.20, P < 0.038), and a high serum potassium level at the start of treatment (per mEq/L; OR: 2.86, 95％ CI: 1.40 - 5.83, P < 0.004). Thus, prior to the initiation of treatment with NM, it is necessary to assess the patient’s medical background and to perform electrolyte monitoring frequently. We suggest that dosage reduction should be considered in the treatment of geriatric patients undergoing long-term treatment with NM.

Palmoplantar pustulosis (PPP) is a chronic inflammatory dermatosis characterized by sterile pustules on the palms and soles. To treat the symptoms, antimicrobial agents such as tetracyclines, macrolides, and cephalosporins are effective for PPP due to their anti-inflammatory effects. To date, there have been no reports on the response rates and time to response of the antibiotics and biomarkers to indicate the severity of PPP. In this study, we retrospectively investigated responsiveness against PPP and possible biomarkers from laboratory test data. During the 5-year study period, 65 PPP patients who visited Asahikawa Medical University Hospital were classified into two groups: non-responders (n = 22) and responders (n = 43). We compared patient background, PPP drugs and laboratory test values between the two groups. Among PPP drugs, the proportion of patients who received antimicrobial agents in the responder group was significantly higher than that in the non-responder group. Among the responder group with antimicrobial agents, the time to response was significantly shorter than that of the responder group without antimicrobial agents. In laboratory values, the changes in the levels of lymphocyte to monocyte ratio (LMR), total protein (TP), and albumin (ALB) in the responder group were significantly decreased compared with those in the non-responder group. These results suggest that antimicrobial agents contribute to the early symptomatic improvement of PPP and shortened the time to response. The reductions in LMR were observed with PPP improvement during the antimicrobial therapy, therefore, this laboratory item has the potential to serve as a biomarker for PPP.

A drug-drug interaction (DDI) caused by a drug combination may cause clinical problems. This study was conducted in patients who were treated in the intensive care unit (ICU) for ≥7 days in our hospital in 2018. The details, frequency and risk factors for potential DDIs were examined at three time points: 24 and 120 hours after ICU admission and at ICU discharge. Lexicomp Drug Interactions, a DDI screening program, was used to detect DDIs. A clinically important DDI was found in 56.1％ of cases, including high rates of DDIs between fentanyl and midazolam, and between prasugrel and heparin. The DDI mechanisms were based on pharmacodynamic interactions in 63.3％ of cases and on pharmacokinetic interactions in 26.7％. The number of drugs used was a common risk factor for a DDI at all three time points in the study. We conclude that an effective pharmaceutical intervention in the ICU requires examination of potential DDIs using a DDI screening program.

We improved the instruction manual and templates for inhaled medication education in the respiratory internal medicine ward. Since September 2017, we have strengthened pharmacist-led inhalation instruction for patients whose outpatient inhaled medications were continued during hospitalization, as well as those who were newly prescribed inhaled medications. Therefore, we examined the necessity of inhaler technique evaluation and re-instruction, and the current state of inhalation instruction. As a method, we evaluated the inhaler techniques of patients whose outpatient inhaled medications were continued during hospitalization. In addition, whenever possible, inhalation instructions and explanations were provided daily to patients following inadequate inhaler techniques and to those who had insufficient understanding of inhaled medications, respectively. Then, we investigated inhaler techniques and understanding, and changes after re-instruction. As a result, there were 55 patients and 73 inhaled medications were evaluated for inhalation upon hospital admission during the study period. The rate of need for re-instruction of inhaler techniques was 43.8％; however, improvements were observed in all aspects of inhaler techniques (including preparation of the drug dose for administration, exhalation, inhalation, confirmation of residual volume, cleanup, and gargling) and those related to knowledge (including the name of the inhaled drug, expected efficacy, dosage and administration, and reason for gargling) after implementation of re-instruction. Therefore, inhalation instructions by pharmacists improved the acquisition and understanding of inhaler techniques, which indicates the necessity of inhaler technique evaluation and re-instruction for patients whose inhaled medications were continued upon hospital admission.

We experienced the administration of chemotherapy to a hemophilia patient with testicular tumors. The patient in this case was a man who was approximately 40 years old. He was being treated under a regimen with factor VIII replenishment prophylactic therapy for Type A hemophilia at our hospital. In January 20XX, this patient was referred to our urology department, complaining of a swollen scrotum, and was diagnosed with a right testicular tumor. A right high orchiectomy was performed in February of the same year. In April of the same year, a Computed Tomography confirmed liver metastasis, and BEP therapy was started as a treatment for postoperative recurrence. During the anticancer treatment, the dosage of the regular supplementation of the freeze-dried concentrated human blood coagulation factor VIII preparations was increased to 1000 units three times per week. If bleeding symptoms associated with hemophilia were found to be confirmed, then a single additional intravenous dose of 1,000 units was administered. We continuously monitored the bleeding symptoms and regularly examined the levels of platelets and APTT, the activation of coagulation factors, levels of hemoglobin, and possible skin-associated symptoms in the patient. If APTT was found to be prolonged for more than 35 s beyond the upper limit of the normal APTT duration, the additional freeze-dried concentrated human blood coagulation factor VIII preparation was administered. As a result, we were able to complete a total of four courses of the BEP therapy without observation of major bleeding in the patient.

In recent years, there has been an increasing number of cases in which anti-cancer drug treatment is performed for patients with reduced physiological functions such as elderly patients and those undergoing maintenance hemodialysis. In systemic chemotherapy for esophageal cancer, a regimen containing 5-fluorouracil (5-FU)has been established as a standard treatment, but a rare side effect is hyperammonemia with impaired unconsciousness. 5-FU is mainly metabolized by liver dihydropyrimidine dehydrogenase (DPD), whereas the catabolic metabolite alpha-fluoro-beta-alanine (FBAL) is excreted in urine. Therefore administration of 5-FU under certain conditions, such as for severe renal dysfunction or to patients undergoing maintenance hemodialysis, may increase FBAL plasma levels and cause hyperammonemia. When FP treatment was administered to patients undergoing maintenance hemodialysis at Kitano Hospital, the plasma ammonia level was high at 1,325 μg/dL and FBAL was high at 33.63 μg/mL on the fourth day. An increase in FBAL may be a cause of hyperammonemia. In patients with reduced renal function or dialysis patients, 5-FU dose reduction should be considered and regular monitoring of ammonia is required.

One-dose packaging improves the convenience of patients in drug therapy and is useful for securing medication adherence. As psychiatric patients take plural, sometimes many, drugs before bedtime, there are increasing demands for utilizing one-dose packaging in dispensing drugs for these patients. Suvorexant is a potent and selective antagonist against orexin 1 and 2 receptors and its use as an insomnia remedy is rising rapidly. On the package insert of suvorexant (Belsomra^®) tablets, there is a description "Store in the press through package (PTP) until use to protect from light and moisture". So far, however, little information has been available about the correct storage conditions regarding the one-dose packaging of Belsomra^® tablets. In this study, we investigated the stability of one-dose packaged Belsomra^® tablets, which were preserved for 30 days at room temperature or at room temperature under 85％ relative high humidity (high humidity), with a focus on the changes in appearance, hardness, mass, disintegration, content, and dissolution. Suvorexant content and the appearance of one-dose packaged Belsomra^® tablets did not change even after 30 days. However, the tablets greatly lost hardness and showed an increase in mass, possibly due to the hygroscopicity of this formulation. These changes resulted in the prolonged disintegration time of one-dose packaged Belsomra^® tablets and in the retarded dissolution of suvorexant from the tablets. These results suggest that Belsomra^® tablets are hygroscopic and less stable. It is, therefore, desirable to avoid long-term, one-dose packaging of this formulation.