Journal of Pharmaceutical Health Care and Sciences最新文献

Background: Toxic epidermal necrolysis (TEN), a severe cutaneous hypersensitivity reaction induced particularly by drugs, is diagnosed when there is a fever of ≥ 38 °C, mucocutaneous symptoms, a rash with multiple erythema, and skin peeling of ≥ 30% of the body surface area. The mortality rate of TEN is high, and thrombocytopenia during treatment can lead to severe outcomes. Intravenous immunoglobulin (IVIg) is used when steroids are ineffective in TEN and may improve mortality; however, thrombocytopenia is a rare adverse event associated with IVIg use. We report the case of thrombocytopenia during IVIg therapy for TEN. We also reviewed previous reports to learn more about the clinical course and mechanism of IVIg-induced thrombocytopenia.

Case presentation: An 83-year-old man with end-stage renal failure on hemodialysis was diagnosed with TEN. After an inadequate response to pulse methylprednisolone therapy, IVIg (400 mg/kg/day) was administered for 5 days. He developed thrombocytopenia after IVIg administration, leading to the diagnosis of thrombocytopenia due to IVIg after excluding other diseases. The platelet count began to increase approximately 10 days after IVIg administration.

Conclusions: When IVIg is administered for TEN, the risk of thrombocytopenia should be recognized and the platelet count should be carefully monitored.

Background: Remdesivir is recommended to treat hospitalized patients with coronavirus disease 2019 (COVID-19). Remdesivir is known to affect glucose metabolism in individuals with and without diabetes. However, little is known about the possibility of hypoglycemia associated with remdesivir. Our case is the first report demonstrating the development of severe hypoglycemia following remdesivir treatment in an elderly man without diabetes.

Case presentation: A 73-year-old man developed COVID-19 following surgery for sigmoid volvulus. The patient's medical history included surgery for posterior correction of scoliosis, Chiari malformation type I, and syringomyelia. There was no history of diabetes mellitus. The patient was started on remdesivir (200 mg on day 1, followed by 100 mg intravenously daily until day 9). On day 7, following remdesivir administration, the patient developed severe hypoglycemia with a blood glucose (BG) level of 25 mg/dL. On day 8 and 9 he repeatedly developed severe hypoglycemia following administration of remdesivir. Considering the timing of administration, the patient's hypoglycemia could have been caused by remdesivir. Therefore, his treatment with remdesivir was discontinued. After discontinuation, his BG levels normalized. The Naranjo algorithm, a tool for evaluating the causality of adverse drug reactions, classified the event as "Probable" (6 points).

Conclusions: Remdesivir may have caused hypoglycemia in this case. Health care professionals should be aware of its potential effects on glucose metabolism and the risk of hypoglycemia when treating patients with remdesivir.

Background: Community pharmacists play a crucial role in promoting medication safety within the community healthcare team. Effective communication by community pharmacists with other health professionals is essential to facilitate the sharing of patient healthcare information. In the context of information sharing between physicians and community pharmacists, assertive self-expression (defined as 'a style of openly expressing one's needs and feelings while respecting others') is beneficial. The aim of this study is to identify factors associated with assertive self-expression among community pharmacists.

Methods: A cross-sectional study was conducted by surveying 3,446 Japanese community pharmacists working at pharmacies across 10 prefectures. Participants were invited to complete a survey form by email and assessed for assertive self-expression using the Interprofessional Assertiveness Scale. Characteristics of participants and pharmacies were compared using univariate analysis. A generalized linear model was used to explore the factors associated with assertive self-expression.

Results: A total of 961 responses by community pharmacists were included in the analysis. Univariate analysis identified significant differences in assertive self-expression scores based on age, employment status, education, years of working experience as a pharmacist, pharmacist home visit service, and participation in joint regional workshops or conferences. After adjustment, participation in joint regional workshops or conferences was significantly associated with assertive self-expression (odds ratio, 1.037; 95% confidence interval, 1.005-1.070; p = 0.023).

Conclusions: This study showed that assertive self-expression among community pharmacists was associated with participation in joint regional workshops and conferences. Further research is needed to examine whether enhancing assertive self-expression facilitates pharmacists' interprofessional communication skills and improves medication safety.

Background: Ensitrelvir is a novel SARS-CoV-2 3-chymotrypsin-like protease inhibitor, similar to nirmatrelvir/ritonavir. Several case reports have demonstrated the efficacy of 3-chymotrypsin-like protease inhibitors in treating prolonged coronavirus disease 2019 (COVID-19) in immunocompromised patients. Tacrolimus (TAC) is a widely used immunosuppressive agent whose blood level can increase significantly due to the inhibition of cytochrome P450 3A (CYP3A) and P-glycoprotein by nirmatrelvir/ritonavir. Since ensitrelvir also inhibits CYP3A and P-gp, similar elevations in TAC levels are expected. A prior case report observed an increase in TAC trough levels with concurrent administration of ensitrelvir. However, no studies have quantitatively described the changes in TAC blood levels and clearances before and after ensitrelvir administration when TAC administration was discontinued to mitigate the drug-drug interaction (DDI) risk; data on safe dosing protocols to avoid the DDI during co-administration of ensitrelvir and TAC remain lacking. Here, we report a case in which TAC levels were successfully managed in a patient with rheumatoid arthritis (RA) who received ensitrelvir for persistent COVID-19 by preemptive discontinuation of TAC and close monitoring of TAC blood levels following ensitrelvir administration.

Case presentation: An 81-year-old Japanese woman who had been administered TAC (1.5 mg once daily) for RA received two courses of remdesivir for moderate COVID-19. However, her viral load remained high and her respiratory status deteriorated. Considering persistent COVID-19, we initiated combination therapy with remdesivir and ensitrelvir (day 0). TAC was discontinued, and the TAC blood levels decreased from 3.6 ng/mL to 1.1 ng/mL over five days. Subsequently, we re-administered TAC (0.2 mg), observing a level of 1.0 ng/mL by day 7. The TAC dose was adjusted to 1.0 mg daily, and TAC levels on day 12 and 14 were 6.5 and 3.7 ng/mL, respectively. TAC (1.5 mg daily) was resumed on day 15. The calculated t_1/2 of TAC were 33.7, 71.9, and 114.6 h from day -1 to 0, day 0 to 2, and day 2 to 5, respectively. The t_1/2 of TAC was extended to 3.4-fold its original duration under ensitrelvir treatment.

Conclusions: This DDI extended the half-life of TAC by approximately 3.4-fold, an effect that gradually diminished over 7 to 10 days. When patients receiving TAC treatment start ensitrelvir therapy, a dose reduction of TAC by approximately one-third to one-fourth is considered appropriate.

Background: Antithrombotic medications are essential for the management of abnormal clot formation. However, their availability, pricing, and affordability in Ethiopia, particularly in Addis Ababa, have not been comprehensively studied.

Methods: A cross-sectional study was conducted in Addis Ababa, Ethiopia to assess the availability, pricing, and affordability of essential antithrombotic medicines. This study utilized the World Health Organization (WHO) and International Health Action Organization methodology. Five public hospital outpatient pharmacies, four private hospitals, ten private pharmacies, four Kenema pharmacies, and two Red Cross pharmacies in Addis Ababa, Ethiopia, were included in the study. All essential antithrombotic medicines in the 6^th edition of Ethiopia's Essential Medicines List were included in this study. Data were collected for originator brands and the lowest-priced generic medicines available at each medicine outlet.

Results: The availability of low-priced generic (LPG) antithrombotic medicines was 31%, with private hospitals having the highest availability (52%). Original-brand antithrombotic medicines were rarely available, averaging only 3%, with private pharmacies showing a slightly higher availability (10%). The median price of LPG antithrombotic medicines is higher in private settings. Original-brand (OB) antithrombotic medicines in private hospitals and pharmacies were unaffordable, costing between 256.14 and 3,418 days of wages.

Conclusion: The availability of most antithrombotic medicines was low across all sectors compared with the WHO target. Private hospitals showed relatively higher availability of LPG medicines than other pharmacy outlets included in the study. There is a significant disparity between the availability and affordability of LPG and OB medicines. To address these issues, the national drug procurement and distribution systems must be strengthened. Exploring local production and financial assistance programs, implementing effective stock management, regulating medicine prices, promoting high-quality generic medicines, and conducting further research to understand the national landscape are all essential.

Background: Continuous subcutaneous administration of injectable opioids is simple and effective; however, skin disorders may occur when high opioid dosages are used. Therefore, we investigated opioid injection drugs with a low risk of skin disorders.

Methods: A retrospective study was conducted using the electronic medical records of patients prescribed 1% hydromorphone hydrochloride or 4% morphine hydrochloride with instructions for continuous subcutaneous administration at Shizuoka Cancer Center from January 2017 to December 2021. The primary endpoint was skin disorders incidence, and the two groups were compared using Cox proportional hazards model analyses and Fisher's exact test at 5% significance level. Patient background factors expected to influence skin disorders were also investigated, and multivariate logistic analysis of skin disorders incidence was performed.

Results: The incidence of skin disorders in the hydromorphone hydrochloride and morphine hydrochloride groups were 3.7% (1/27 patients) and 28.1% (9/32 patients), respectively, showing a significant difference in two statistical analyses between the two groups (Cox proportional hazards model analyses HR: 0.09, 95% CI: 0.01-0.70, P = 0.022. Fisher's exact test OR: 0.10, 95% CI: 0.01-0.84, P = 0.016). In the multivariate analysis, the administration of hydromorphone hydrochloride (OR: 0.04, 95% CI: 0.003-0.48, P = 0.012) was also found to have a significant negative correlation with the occurrence of skin disorders. On the contrary, administration period ≥ 28 days (OR: 18.16, 95% CI: 2.22-148.60, P = 0.007) was a factor with a significant positive correlation.

Conclusions: Subcutaneous 1% hydromorphone hydrochloride administration had a lower risk of skin disorders than 4% morphine hydrochloride injection. Moreover, prolonging the administration period increased the risk of developing skin disorders. This suggests that a 1% hydromorphone hydrochloride Injection is a good clinical decision for patients who are likely to have a longer administration period and require a higher dosage of injectable opioids.

Trial registration: Retrospectively registered.

Background: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, offering hope for various malignancies by enhancing the immune response against tumors. However, ICIs are associated with unique immune-related adverse events (irAEs), which differ significantly from conventional chemotherapy-induced toxicities. These irAEs, which affect more than 70% of patients and often escalate to severe grades, present substantial clinical management challenges and frequently necessitate emergency hospitalization. Therefore, this study aimed to investigate the clinical characteristics of patients requiring emergency hospitalization due to irAEs during ICI therapy to enhance understanding and improve management strategies.

Methods: This retrospective study evaluated patients who received ICIs at Iwate Medical University Hospital between August 1, 2016, and December 31, 2022, and required emergency hospitalization due to irAEs. Clinical data were extracted from the medical records, including patient demographics, presenting complaints, time from ICI initiation to hospitalization, irAE diagnoses, and treatment outcomes. The Spearman rank correlation coefficient was used to analyze the associations between the chief complaints and irAE diagnoses.

Results: Of 1009 ICI-treated patients, 96 required emergency hospitalization for irAEs. The cohort's mean age was 73 years, with 75.0% of patients being male. Among patients who required emergency hospitalization, a high proportion were undergoing treatment for lung cancer (41.7%). The median hospitalization duration was 87 days. The chief complaints included dyspnea (34.4%) and fatigue (34.4%), with gastrointestinal and respiratory disorders being the most frequent irAEs (35.4%). Significant correlations were observed between dyspnea and respiratory diseases (Rs = 0.66), skin diseases and disorders (Rs = 0.81), pain and musculoskeletal disorders (Rs = 0.59), and diarrhea and gastrointestinal disorders (Rs = 0.49). Corticosteroids were administered to 64.6% of the patients. Despite emergency interventions, 8.3% of patients succumbed to irAEs, while 33.3% resumed ICI therapy after hospitalization.

Conclusions: Emergency hospitalization due to irAEs is a considerable concern in ICI therapy, occurring in 9.5% of treated patients. The high incidence of severe irAEs within the first 3 months of treatment underscores the need for early and vigilant monitoring. This study highlights the importance of recognizing and promptly managing irAEs to improve patient outcomes. Future strategies should focus on developing comprehensive management frameworks and enhancing patient and caregiver education to recognize symptoms that warrant immediate medical attention.

Background: In the dose titration of transdermal fentanyl to prevent unrelieved pain, it is important to consider not only dose adjustment, but also the titration period, which is influenced by the time required to reach the steady state. Many patients with cancer pain experience comorbidities that might affect the skin properties and influence transdermal absorption. We hypothesized that skin changes due to diabetes mellitus (DM) would affect the titration period of transdermal fentanyl. We conducted a retrospective study and diabetic animal model study to test this hypothesis.

Methods: In the retrospective study, the titration period was defined in terms of "dose change" and "number of rescue opioids" in patients initiated on transdermal fentanyl. Multiple logistic regression analysis was performed to analyze the relation between the titration period and comorbidities, including DM. In the diabetic animal model study, intercellular lipids of stratum corneum (SC) were analyzed in Goto-Kakizaki (GK) rats, a model of DM, and the pharmacokinetics of intravenously or transdermally administered fentanyl was examined.

Results: In the retrospective study, the titration period ranged from 5 to 39 days (n = 387), and the patients taking a longer period (6 days or more) was significantly related to in patients with unspecified DM: AOR (95% confidence interval), 0.438 (0.217-0.884). In the diabetic animal model study, the ceramides (CERs) content in the SC was decreased by approximately 30% in GK rats compared to Wistar rats. The absorption rate constant (k_a) of fentanyl administered transdermally was increased approximately 1.4-fold in GK rats, though there was no difference in transdermal bioavailability (F) or systemic clearance (CL_tot).

Conclusion: Our results suggest that the steady state of transdermally administered fentanyl is reached sooner in cancer patients with DM as a comorbidity. Earlier pain assessment and dose adjustment may be possible in these patients.

Adverse events (AEs) induced by cancer chemotherapy reduce not only patient quality of life (QOL) but also the efficacy of treatment. Management of AEs can therefore improve both the efficacy and safety of cancer chemotherapy. This review describes the contribution of pharmacists to the management of adverse events aimed at improving the treatment efficacy of cancer chemotherapy. Efforts to improve the evidence-practice gap are a useful approach to countermeasures against AEs. Pharmacists can intervene in these efforts in the course of their daily practice. Here, we made undertook to improve the evidence-practice gap in prophylaxis pharmacotherapy for chemotherapy-induced nausea and vomiting (CINV) and anti-EGFR antibody-induced acneiform rash. After intervention by pharmacists, the rate of adherence to prophylaxis pharmacotherapy for these AEs was significantly improved, and the incidence of CINV and acneiform rash was significantly decreased. Notably, time to treatment failure (TTF) with anti-EGFR antibody therapy tended to be increased, and may have contributed to an improvement in therapeutic effect. Next, we examined adverse events associated with anti-cancer drugs related to the therapeutic effect of cancer chemotherapy. Incidence of hypomagnesemia in patients receiving anti-EGFR antibodies and neutropenia in patients receiving TAS-102 was significantly associated with the therapeutic effect of cancer chemotherapy. Moreover, we examined the impact of cancer cachexia, a cancer-associated AE, on the therapeutic effect of immune checkpoint inhibitors. In patients receiving nivolumab, the presence of cancer cachexia prior to treatment initiation was associated with shorter OS and TTF. In summary, pharmacist management of AEs was shown to improve treatment response. Further, AEs which are predictive of treatment response in cancer chemotherapy were identified. Management of these AEs is an important role for pharmacists aiming to improve patient QOL and treatment efficacy.