Our results support more frequent monitoring of serum calcium concentrations at baseline and during the first 2 weeks of treatment in patients receiving denosumab, especially those with an eGFR <30 mL/min.

Opioid-induced respiratory depression is a potentially life-threatening adverse drug event. The purpose of this study was to evaluate the incidence of respiratory depression using the Japanese Adverse Drug Event Report (JADER) Database to obtain data to promote proper use of opioids. The JADER database from April 2004 to March 2017 was obtained from the Pharmaceuticals and Medical Devices Agency. We calculated the reporting odds ratios (RORs) of suspected opioids (morphine, fentanyl, oxycodone, tapentadol, methadone, tramadol, pentazocine, buprenorphine, and codeine phosphate hydrate), analyzed the daily dose at first appearance and the time-to-onset profile, and assessed the hazard type using the Weibull shape parameter. ROR analysis detected adverse event signals for all opioids. Morphine showed a large ROR value with statistical significance in elderly (≥70 years old) patients. The median daily doses of oral morphine and oxycodone for inducing respiratory depression were comparably low (30 mg/d as oral morphine equivalent dose), while that of transdermal fentanyl was 120 mg/d (oral morphine equivalent dose). On time-to-onset analysis using the Weibull distribution, those opioids were classified as the early failure type. The median time-to-onset of oral morphine, oral oxycodone and transdermal fentanyl was 5.5, 11 and 12.5 d, respectively, and almost 50% of cases were reported within 30 d. Taken together, our results suggest that it is important to monitor patients carefully for at least the first one week to one month, even if opioids are administered at a relatively low dose, especially in elderly patients administered morphine.

Background: Development of acute kidney injury (AKI) depends on the severity of renal dysfunction, clinical setting, comorbid factors, and geographical location. Gastric cancer is one of the deadliest malignancies worldwide, and its incidence is significantly high in Japan. Objective: We analyzed the rank-order of the association of anticancer agents for gastric cancer with AKI using a spontaneous reporting system database, the Japanese Adverse Drug Event Report database. Methods: We performed a retrospective pharmacovigilance disproportionality analysis using the adverse event reports submitted to the Pharmaceuticals and Medical Devices Agency between April 2004 and March 2017. Results: Anticancer drug-related AKI was common in patients in their 60s and 70s (39.2% and 43.2%, respectively). AKI occurred most frequently within 1 month after anticancer drug administration. The signals of AKI were reported after treatment with S-1 (tegafur/gimeracil/oteracil), cisplatin (CDDP), and capecitabine, with significant adjusted reporting odds ratios (95% CI) of 1.50 (1.09-2.07), 3.43 (2.48-4.74), and 1.82 (1.15-2.90), respectively. CDDP-induced AKI was more likely to occur in patients who were male, hypertension, or diabetes mellitus. Conclusion and Relevance: This study showed that most AKI cases were related to S-1 and/or CDDP adjuvant chemotherapy for gastric cancer treatment. The data also clarified that AKIs occurred within 1 month and that their clinical outcomes were more severe than previous reports of drug-induced AKI in general medicine. Our study provides useful information to minimize the risks of administration to patients at high risk for S-1 and/or CDDP containing chemotherapy–induced AKI.

Oxaliplatin is an essential drug in the chemotherapy of colorectal, gastric, and pancreatic cancers, but it frequently causes peripheral neuropathy as a dose-limiting factor. So far, animal models of oxaliplatin-induced peripheral neuropathy have been established. The mechanisms of development of neuropathy induced by oxaliplatin have been elucidated, and many drugs and agents have been proven to have neuroprotective effects in basic studies. In addition, some of these drugs have been validated in clinical studies for their inhibitory effects on neuropathy. In this review, we summarize the basic and clinical evidence for the therapeutic effects of oxaliplatin. In basic research, there are many reports of neuropathy inhibitors that target oxidative stress, inflammatory response, sodium channel, transient receptor potential (TRP) channel, glutamate nervous system, and monoamine nervous system. Alternatively, very few drugs have clearly demonstrated the efficacy for oxaliplatin-induced peripheral neuropathy in clinical trials. It is important to activate translational research in order to translate basic research into clinical research.

Background There is no nationwide data on polypharmacy in palliative care in Japan. In this study, the research committee of the Japanese Society for Pharmaceutical Palliative Care and Sciences conducted an online survey on polypharmacy and inappropriate prescriptions involving its members who worked as hospital pharmacists. Methods The online questionnaire included questions about hospital pharmacist interventions for cancer patients who regularly used six or more drugs during a two-month period from October to November 2017. Results Of 2618 hospital pharmacists, 359 responded (13.7%). With regard to cancer patients receiving opioids, 40.9 and 22.3% of the respondents replied that percentages of patients prescribed six or more regular medications were “40–69%” and “70–99%,” respectively. Regarding patients on polypharmacy, 73.0% of the respondents reported a low or moderate rate of inappropriate prescriptions, with responses such as “long-term administration of irresponsible or aimless medications”, “adverse drug reactions,” and “duplication of the pharmacological effect”. Furthermore, 24.2, 46.8, and 23.4% of respondents replied that the rates of drug reduction due to pharmacist recommendations were “0”, “1–39%”, and “more than 40%,” respectively. Pharmacist interventions decreased the use of inappropriate medications, including antiemetics, gastrointestinal medications, and hypnotic sedatives, and reduced or prevented adverse drug reactions such as extrapyramidal symptoms, delirium, and sleepiness. Similar results were obtained for cancer patients who did not use opioids. However, the rates of cancer patients on polypharmacy and with reduction of inappropriate medications by pharmacist interventions were significantly higher in cancer patients receiving opioids. Finally, recommendations of board-certified pharmacists in palliative pharmacy contributed to a decrease in the use of inappropriate medications in cancer patients on polypharmacy ( p = 0.06). Conclusion This nationwide survey clarified pharmacist interventions for polypharmacy in palliative care in Japan. Our data showed frequent polypharmacy in cancer patients receiving opioids, and benefits of pharmacist interventions, especially by board-certified pharmacists in palliative pharmacy, for reducing inappropriate medications and improving adverse drug reactions. Trial registration The study approval numbers in the institution; 0046. Registered November 6, 2017. Electronic supplementary material The online version of this article (10.1186/s40780-019-0143-5) contains supplementary material, which is available to authorized users.