Adverse Events Associated with Ethical Kampo Formulations: Analysis of the Domestic Adverse-Event Data Reports of the Ministry of Health, Labor, and Welfare in Japan

Abstract

Objectives. Traditional Japanese Kampo medicines have been integrated into the Japanese national health-care system. In Japan, the Ministry of Health, Labor, and Welfare’s website discloses adverse drug-event data that have been obtained from medical personnel reports investigated by the Pharmaceutical and Medical Devices Agency. Using these data, we investigated adverse events associated with ethical Kampo formulations. Methods. Reports of adverse events associated with ethical Kampo formulations from the domestic adverse-event data were obtained from July 30, 2003, to March 31, 2018. Adverse events were then categorized, and the relationships between categories of adverse events and crude drugs were analyzed. Results. There were 4,232 reported adverse events associated with ethical Kampo formulations. The numbers of events by category were as follows: events related to liver injury, 1,193; lung injury, 1,177; pseudoaldosteronism, 889; mesenteric phlebosclerosis, 223; drug eruption, 185; and others, 565. Among events related to both liver injury and lung injury, approximately 70% were suspected to be induced by Kampo formulations containing Scutellariae Radix. The pseudoaldosteronism-related events, which are induced by Glycyrrhizae Radix, included several events related to muscle injury, heart failure, and arrhythmia. Events related to mesenteric phlebosclerosis, believed to be induced by long-term use of Kampo formulas containing Gardeniae Fructus, increased remarkably during the study period. Among the events related to drug eruption, approximately 35% were suspected to be induced by Kampo formulations containing Ephedrae Herba. Conclusion. Kampo medicines may cause various adverse events. The present results provide valuable information regarding adverse events associated with Kampo medicines from the viewpoint of patient safety.

The use of Traditional Chinese Medicines to treat SARS-CoV-2 may cause more harm than good

“…Larger cohorts and greater numbers now support this crucial relationship. In a Japanese cohort of 73 patients, pneumonitis development occurred within 3 months of commencing traditional medicine in the majority of patients [3], while a large report from the Japanese Ministry of Health, Labor and Welfare, described more than 1000 cases of lung injury secondary to traditional medications, the overwhelming majority of which (852 reports) were described as 'interstitial lung disease [4].…”

The effect of Hangeshashinto on Oral Mucositis Caused by Induction Chemotherapy in Patients with Head and Neck Cancer

“…TJ-14 contains Coptidis Rhizoma and Glycyrrhizae Radix, which have been shown to induce side effects such as pseudoaldosteronism and herbal medicine-induced pneumonitis. 14,15 One study reported that TJ-14 may have been associated with liver injury. 9,15 More importantly, however, previous studies that demonstrated side effects used oral administration of TJ-14.…”

“…14,15 One study reported that TJ-14 may have been associated with liver injury. 9,15 More importantly, however, previous studies that demonstrated side effects used oral administration of TJ-14. In our study, patients gargled the medication, which is a safer and more effective method of administration for head and neck cancer patients.…”

“…20,21 It has been suggested that the development of OM during chemotherapy occurs due to the cyclooxygenase pathway, which mediates tissue injury and pain by upregulating PGE2 and proinflammatory cytokines. 15 TJ-14 has been reported to have anti-inflammatory effects in both in vivo and in vitro studies. 22,23 We speculate that the effects of TJ-14 in head and neck cancer are similar to those in other cancers.…”

Kampo for the Treatment of Pain in Japan: A Review

“…Physicians should note that previous studies have revealed not only clinical usefulness of Kampo medicines to improve several clinical manifestations but also possible adverse effects. A recent review article reports that frequent events caused by Kampo medicines include liver injury (28.2%) followed by lung injury (27.8%), psedoaldosteronism (21.0%), mesenteric phlebosclerosis (5.3%), drug eruption (4.4%), and others (13.3%) [48]. Since the classification of types of adverse reactions; acute, bizarre, chronic, or delayed onset, is applied both in Western drugs as well as Kampo herbs [49], it is important to note that pharmacotoxicity of Kampo herbs can occur at any timing.…”