Investigation of the boxed warnings in package inserts of prescription medicines for medical professionals in Japan

Main Article Content


Boxed warning, Japanese Pharmaceutical Act, Package insert, Precaution part, Response part


Objective: In the Japanese Pharmacists Act, article 25-2, revised in 2013, it states that pharmacists shall provide the necessary information and guidance to the patient based on pharmaceutical knowledge and experience for ensuring the proper use of the medicine dispensed. The package insert is one of the documents to be referred to when providing the information and guidance. The boxed warnings in package inserts that include the precautions and responses are the most significant parts, however, the suitability of boxed warnings for pharmaceutical practice has not been evaluated. The aim of this study was to investigate the boxed warning descriptions in package inserts of prescription medicines for medical professionals in Japan. Methods: Package inserts of prescription medicines listed in the Japanese National Health Insurance drug price list on March 1st 2015 were collected one by one by hand from the website of the Japanese Pharmaceuticals and Medical Devices Agency ( Package inserts with boxed warnings were classified according to the Standard Commodity Classification Number of Japan based on the pharmacological activity of each medicine. They were also compiled according to their formulations. The boxed warnings were divided into the precautions and responses parts, and their characteristics were compared among medicines. Results: The number of package inserts found on the website of the Pharmaceuticals and Medical Devices Agency was 15,828. Boxed warnings were present in 8.1% of the package inserts. A description of adverse drug reactions accounted for 74% of all precautions. Most of the precautions were observed in the warning boxes of antineoplastic agents. Blood and lymphatic system disorders were the most common precaution. Responses in the boxed warnings directed toward medical doctors, pharmacists, and other healthcare professionals accounted for 100, 77, and 8% of all package inserts with a boxed warning, respectively. Explanations for patients were the second most frequent response. Conclusions: The majority of boxed warnings request therapeutic contribution by pharmacists, and the descriptions of these explanations and guidance by pharmacists to patients were found to be consistent with the Pharmacists Act.

Abstract 1250 | PDF Downloads 483


1. Eshtayeh M, Draghmeh A, Zyoud SH. A comparative evaluation of medicine package inserts for oral antidiabetic agents in Palestine. BMC Public Health. 2019;19(1):1037.
2. Eteraf-Oskouei T, Abdollahpour S, Najafi M, et al. Do drug package inserts meet the rules and regulations of Iran’s Food and Drug Administration in terms of informing patients? Health Promot Perspect. 2019;9(3):214-222.
3. Bian J, Chen B, Hershman DL, et al. Effects of the US Food and Drug Administration boxed warning of erythropoietin-stimulating agents on utilization and adverse outcome. J Clin Oncol. 2017;35(17):1945-1951.
4. Morant AV, Jagalski V, Vestergaard HT. Labeling of disease-modifying therapies for neurodegenerative disorders. Front Med (Lausanne). 2019;6:223.
5. Outline of Post-marketing Safety Measures; Pharmaceuticals and Medical Devices Agency Website ( nglish/safety/outline/0001.html)6. Japanese Law Translation Database System (
7. Ministry of Internal Affairs and Communications Website (
8. Diasio RB. Sorivudine and 5-fluorouracil; a clinically significant drug-drug interaction due to inhibition of dihydropyrimidine dehydrogenase. Br J Clin Pharmacol. 1998;46(1):1-4.
9. Japanese Law Translation Database System (
10. Pharmaceuticals and Medical Devices Agency Website (
11. ICH MedDRA Website (
12. Package insert of 5-FU Injection; Pharmaceuticals and Medical Devices Agency Website (Japanese text only) (

Most read articles by the same author(s)

1 2 3 4 5 6 7 8 9 10 > >>