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.

Background: Hydromorphone is an analogue of morphine used in the treatment of cancer-related pain. There have been few studies that have evaluated the analgesic effect upon transition from hydromorphone injections. The aim of this study was to evaluate the conversion ratio between injection and oral preparation. Methods: We conducted a retrospective chart study of consecutive patients who were admitted to our hospital between July 2018 and December 2019. Results: In six patients, when the conversion ratio from hydromorphone injection to oral was changed at a 1:5 conversion ratio, three patients obtained adequate analgesic effects, the analgesic effect was insufficient in one case and an increased dose was required. Significant drowsiness appeared in two patients who required a decrease in dose. Conclusions: In converting from hydromorphone injections to oral preparations, it is necessary to carefully monitor the analgesic effect and adverse events and adjust the dosage for each case regardless of the conversion ratio.