[New Opioid Options in Japan - Methadone, Tapentadol and Hydromorphone]

In 2010s, several opioids became available in Japan, including methadone, tapentadol and hydromorphone. Methadone was approved in September 2012 by Japanese regulatory authority. Since methadone is positioned as so-calledstep 4 opioidin Japan, it must be prescribed as alternative opioid switched from another of 60mg/day or greater equivalent dose of oral morphine. Diversity of pharmacokinetics among individuals and various drug interactions require close monitoring of adverse events. In spite of these cautions, unique characteristics such as inhibiting N-methyl-D-aspartate(NMDA)and in- ducing internalization/degradation of mu-delta opioid receptor heterodimers underline the value of methadone in opioid switching. Tapentadol, a dual-acting opioid which inhibits noradrenaline(norepinephrine)reuptake, was approved in Japan in March 2014. In a double-blind randomized study comparing with oxycodone, tapentadol showed relatively better tolerability. Advantages such as having no active metabolites and minimal drug interactions also ease the administration of tapentadol to the patients with comorbidities. Hydromorphone, approved in March 2017, has a profile similar to morphine. Higher potency than morphine lead to less production of 3-glucronide metabolite(H3G)which accumulates in patients with renal failure and causes neurotoxicity. Because there is no concluding evidence about effect of hydromorphone on dyspnea or tolerability in patients with renal insufficiency, organized studies are still needed. We expect these "new in Japan" opioids contribute to long-term, stable pain control for patients with cancer.