Objective: For safe use of drugs, it is indispensable to carry out proper and continuous risk management throughout preclinical to post-marketing phases.  In Japan, denosumab, a novel anti-RANKL antibody for treatment of bone metastasis, was approved in April 2012.  Since beginning of clinical use, severe hypocalcemia has been reported as adverse drug reactions.  In this study, the role of pharmacists in minimization of risks of newly introduced drugs was examined using denosumab as an example.
Methods: Firstly, the description on prevention of hypocalcemia in approval review report and different versions of drug package inserts of denosumab were compared.  Secondly, the differences in ratio of hypocalcemia in patients using denosumab with or without concomitant use of Ca and vitamin D preparations in Kobe City Medical Center General Hospital between April 2012 and July 2013 were examined.
Results: During the few months after beginning of clinical use of denosumab, many cases on the onset of severe hypocalcemia induced by denosumab had been reported.  Therefore, drug package insert was revised to enhance and recommend Ca and vitamin D supplementation.  Before the in-house enforcement in our hospital, of 26 patients, 6 patients were administered with denosumab without Ca and vitamin D preparations and 2 of them developed hypocalcemia over Grade 3.  After the in-house enforcement, no significant changed in serum Ca level in the 20 patients with Ca and vitamin D preparations were observed.
Discussion: Severe side effects can be avoided if hospital pharmacists take appropriate measures based on rational evaluation of proper information.
Conclusions: For risk minimization, pharmacists must evaluate and manage the risks of newly introduced drugs.

The aim of this study was to examine the usefulness of opioid initiation therapy with oral tramadol (TD) by comparing its efficacy and safety with that of sustained-release oxycodone (OXC). Although the complexity of clinical setting seemed to make difficult to carry out strict evaluation of TD initiation therapy, a higher number of patients experienced unmanageable pain with TD initiation therapy than with OXC. Almost half the TD-initiated patients switched from TD to another analgesic in earlier phase than those on OXC did. However, the number of patients who changed the initiation opioid because of side effects was larger with OXC than it was with TD. The incidence of nausea and sleepiness was significantly lower with the TD initiation therapy than it was with OXC. Additionally, cases of nausea observed after OXC administration were also significantly fewer in patients who switched opioids from TD to OXC than in the OXC-initiated patients. In the case of OXC-initiation, the number of onset of side effects was the highest immediately following opioid initiation, and then it gradually decreased. However, in switched case from TD to OXC, they mostly did not develop side effects after OXC administration. These results suggest that opioid initiation with TD could be a useful alternative for pain management with fewer side effects; however, careful monitoring of pain relief is essential, especially in the early phase of TD initiation.

Objective: In many medical institutions in Japan, 10% lidocaine gel is prepared as an in-hospital formulation to treat intractable neuropathic pain. Clinical studies have reported the short-term efficacy of topical lidocaine therapy for neuropathic pain, while there are few reports in real-world practice. To clarify the clinical usage and its usefulness, in this study, we investigated the duration of use, amount, effectiveness, and safety of 10% lidocaine gel.Design: We conducted a retrospective study investigating the actual usage of 10% lidocaine gel using electronic medical records.Methods: This study included 74 patients treated with 10% lidocaine gel in Kyoto University Hospital between July 2019 and January 2022. Information about disease (purpose of use), concomitant medications and other background information of the patients were collected. In addition, the duration of use, amount, adverse events, and discontinuation of 10% lidocaine gel were investigated. Effectiveness was determined by physician interviews and the pain visual analogue scale (VAS).Results: Ten percent lidocaine gel was used primarily to treat postherpetic neuralgia and, in some cases, other types of chronic pain for a median duration of use of 3.2 months (0.03-118.5). Pain relief was achieved in 73.3% of patients according to physician interviews, with a significant decrease in the VAS score. Although adverse events were observed in 12 patients (16.2%), including skin problems (12.2%), paralysis (4.1%), and somnolence (1.4%), eight patients continued to use 10% lidocaine gel after their occurrence. Three patients discontinued it due to adverse events, and their symptoms subsequently improved thereafter.Conclusion: The present results suggest that 10% lidocaine gel is effective and safe even when used for a long-time. Although this is a single-center study, it is the first systematic investigation of real-world usage of an in-hospital formulation of 10% lidocaine gel and is expected to assist clinical practice and drug development.

Objective: In patients with specific backgrounds, comprehensive identification of health problems and proactive pharmacist intervention are crucial to providing safe and effective medical care. However, there are insufficient reports on chemotherapy regimen selection and supportive care management in patients taking immunosuppressants. In this study, to circumvent adverse events, pharmacists intervened with a patient administering tacrolimus (TAC) using known information, focusing on multiple factors attributable to the patient in addition to drug interactions.Methods: The patient was a male in their 70s who received palliative chemotherapy for gastric cancer during their dermatomyositis treatment with TAC. Pharmaceutical support for cancer chemotherapy was provided using the following four procedures: (1) Patient information was collected from interviews and electronic medical records to identify patient-specific problems; (2) Basic pharmacological information was collected from tertiary sources, focusing on the interaction between TAC and aprepitant (APR). Furthermore, clinical reports were collected, and the pharmacokinetic drug interaction significance classification system was used for quantitative predictions; (3) The information obtained in steps 1) and 2) was evaluated, and comprehensive proposals linked to the patient information were presented; (4) Adverse events, TAC blood level, and patient outcomes were monitored after treatment initiation.Results: A chemotherapy regimen consisting of S-1/oxaliplatin therapy without APR was selected. The adverse effects were controllable, and the treatment was completed without many adverse events. Meanwhile, TAC adherence was unaffected by cancer chemotherapy, and the TAC blood concentration or dose ratios were controlled within the same range as previously reported.Conclusion: In cancer chemotherapy, for cases with limited evidence or information, comprehensive pharmaceutical support was provided using known patient information, considering multiple patient factors. This report is beneficial as an example of supportive care management by a pharmacist and contributes to providing optimal service in cases with specific backgrounds.