April 1, 2021

Kampo medicines and incident reporting system in Japan: Role of PMDA
Kampo medicine is a traditional Japanese medicine that originated from traditional Chinese
medicine and uniquely developed after being introduced into Japan. Currently in Japan, Kampo
medicines are available not only as over-the-counter drugs, but also as prescription drugs (i.e., ethicaldrugs). Indeed, Kampo medicines have been integrated into the national Japanese health-caresystem. At present, 148 Kampo extract formulations and approximately 200 types of crude drugs
have been approved by the Ministry of Health, Labor, and Welfare (MHLW) and are being used under
the national health-insurance program.
There is no medical license specific to Kampo medicine in Japan, so it is possible for physicians
who are not Kampo medicine specialists (not certified by the Japan Society for Oriental Medicine) toprescribe Kampo medicines. The development of modern, ready-to-use forms of Kampo medicines
has resulted in increased usage, mainly of spray-dried granular extracts of the original formulas.
Kampo extracts for ethical use have largely replaced traditional decoctions of the crude drugs, eventhough crude drugs are also covered by the national health-insurance system. Japanese physicianswith limited knowledge of Kampo medicine tend to prescribe ethical Kampo extracts, rather than crude
drugs for decoction, mainly based on their knowledge of conventional Western medicine. The
application of ethical Kampo formulations has steadily increased in recent decades, and according toa survey conducted by the Japan Kampo Medicines Manufacturers Association, 89.0% of physiciansprescribed Kampo medicines in their daily medical practices in 2011.
It was long thought that Kampo medicines had a mild effect and were rarely associated withadverse events. Historically, reported Kampo medicine-induced adverse events included
pseudoaldosteronism caused by Glycyrrhizae Radix (kanzo in Japanese), sympathomimetic effects
caused by Ephedrae Herba (mao in Japanese), and aconite intoxication caused by Aconiti Tuber(bushi in Japanese). However, it has become clear that Kampo medicines can be accompanied bymore serious adverse events. In recent decades, it has been reported that Kampo medicines cancause liver and lung injury, and an etiological relationship between these injuries and Scutellariae
Radix (ogon in Japanese) has been strongly suspected. Furthermore, mesenteric phlebosclerosis
has been reported to be associated with long-term use of Kampo formulas containing Gardeniae
Fructus (sanshishi in Japanese).
In Japan, all drugs inclusive of Kampo medicines causing adverse events, including suspectedcausal drugs and drugs for which a causal relationship cannot be ruled out, should be reported to thePharmaceutical and Medical Devices Agency (PMDA) by pharmaceutical companies, attending
physicians, or pharmacists who first identify them. The PMDA was established in 2004 and provides
drug-safety information on their website (https://www.pmda.go.jp/english/index.html). In addition, theMHLW website has published adverse-event data reports on ethical drugs and over-the-counter drugs
since July 30, 2003; these data were obtained from medical personnel reports investigated by thePMDA, which are released approximately every 4 months. Kampo medicines are also included in theinformation without exception.
We reported the adverse events associated with ethical Kampo formulations by analysis of thedomestic adverse-event data reports of the Ministry of Health, Labor, and Welfare in Japan(https://doi.org/10.1155/2019/1643804).
We reviewed adverse effects of Kampo medicines (https://doi.org/10.2169/internalmedicine.6292-20).
Department of Japanese Oriental Medicine, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama