Package Insert Revisions Research Articles

Prescription trend and lactic acidosis in patients prescribed metformin before and after the revision of package insert for allowing metformin administration to patients with moderately decreased kidney function based on real-world data from MID-NET® in Japan.

This study was conducted to understand the impact of package insert (PI) revision in Japan on 18 June 2019 to allow metformin use for patients with moderately decreased kidney function (30 ≤ estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2). A new user cohort design was employed to examine the prescription trend and the occurrence of lactic acidosis in patients prescribed metformin before and after PI revision using the Medical Information Database Network (MID-NET®). From 12 May 2016 to 31 March 2020, 5,874 patients (before, n = 4,702; after, n = 1,172) were identified as new metformin users, including 1,145 patients (before, n = 914; after, n = 231) with moderately decreased kidney function. Although no marked changes in metformin prescription were observed before and after PI revision, the daily metformin dose at the first prescription decreased after PI revision. For both before and after PI revision, less than 10 cases of lactic acidosis occurred in all patients prescribed metformin, and no lactic acidosis was observed in patients with moderately decreased kidney function. The results of this study are useful for understanding the safety of metformin use in patients with decreased kidney function and suggest no worse impacts of PI revision in Japan, indicating no further safety concerns on metformin use in patients with moderately decreased kidney function under the situation with careful use and safety monitoring of metformin.

Detection of Vaccine Adverse Events Before Package Insert Revisions Using a Japanese Spontaneous Reporting System.

The usefulness of disproportionality analysis for the pharmacovigilance of vaccines in the Japanese Adverse Drug Event Report (JADER) database is yet to be proven. This study aimed to verify whether significant disproportionality could be detected before adding new vaccine adverse event information to package inserts. Information on package insert revisions related to vaccine adverse drug events from January 2013 to March 2023 was extracted from the Pharmaceuticals and Medical Devices Agency website. This period was set as the maximum period for which early disproportionalities could be detected by the latest JADER database (April 2004 to December 2022). From JADER data, 15 revision histories (10 types of vaccines) of package inserts were identified, and 823,662 cases were obtained. Of the 15, 12 (80%) adverse events were identified as significant disproportionalities before package insert revisions were made. Nine of the 15 (60%) events were identified as significant disproportionalities earlier than at least 12 months. These findings suggest that the JADER database may detect vaccine adverse events earlier than package insert revisions, indicating its usefulness for the safety surveillance of vaccines.

PMDA recommends package insert revisions for five products

PMDA recommends package insert revisions for five products

Package insert revisions recommended by PMDA

Package insert revisions recommended by PMDA

Does Industry-Conducted All-Case Surveillance of Newly Approved Oncology Drugs Contribute to the Revision of Package Inserts in Japan?

In Japan, the Pharmaceuticals and Medical Devices Agency requires all‐case surveillance studies (ACSS) for many novel oncology drugs as a condition for approval. However, this is a major burden on the pharmaceutical industry and clinicians. The objective of this analysis was to investigate whether ACSS can contribute essential new information on severe adverse drug reactions, which are necessary to revise the package inserts of drugs. All oncology drugs for which ACSS were required from January 2006–September 2015 found on the Pharmaceuticals and Medical Devices Agency website were reviewed, and the influence of ACSS on the package insert content was evaluated. Most of the package insert revisions regarding serious treatment‐related adverse events were based on spontaneous reports from clinicians. The contribution of ACSS results to the revision of package inserts is limited and comes at the cost of financial resources and labor. An alternative, more efficient adverse‐event reporting system is necessary.

Influence of Drug Lag on New Drug Label Revisions.

Drug lag (DL) in Japan has decreased in the last few years as a result of the globalization of drug development in the past decade, and new molecule entities (NMEs) with short DL are on the rise. The purpose of this study was to investigate the influence of DL on postmarketing safety of NMEs, by comparing the length of DL and the chronological trend of package insert revisions. The number of label revisions occurring during 6 years after approval was investigated for 142 NMEs approved between 2000 and 2006. The NMEs were classified by the length of DL (2 years and 4 years), and the label revision trends by each label section and therapeutic categories were analyzed. The cumulative number of level revisions in the "Drug Interactions" and "Clinically Significant Adverse Reactions" sections in the first year after approval in the DL <2 years group was significantly greater than in the DL ≥2 years group. In the chemotherapeutic category that showed the shortest DL, the first label revision occurred in 33.3% within the first year and in 66.7% by the second year, and label revisions were performed earlier than in any other therapeutic categories. These results suggest that the package inserts of NMEs with a shorter DL tend to be revised earlier and more frequently, and it requires more careful monitoring of safety information after product launch.

First batch of Japanese package insert revisions for 2019

First batch of Japanese package insert revisions for 2019

Package insert revisions for three therapies in Japan

Package insert revisions for three therapies in Japan

PMDA: necessary package insert revisions from April 2018

PMDA: necessary package insert revisions from April 2018

Recent package insert revisions recommended by PMDA

Recent package insert revisions recommended by PMDA

Package insert revisions recommended by PMDA

Package insert revisions recommended by PMDA

PMDA: package insert revisions needed for four drugs in Japan

PMDA: package insert revisions needed for four drugs in Japan

Thinking on revision of package insert of levofloxacin oral and injection preparations

Thinking on revision of package insert of levofloxacin oral and injection preparations

後発医薬品の供給体制，医薬品情報，包装単位についての調査

We surveyed some significant factors related to the use of generic drugs, such as the stability of supply, the timeliness of package insert revisions, the existence and/or contents of “Interview Forms” (IF), the unit sizes and the locations of marketing offices. The drugs on which information was collected for this survey were 1) those normal carried by our hospital and had generic equivalents, and 2) those among the top 5 products both in terms of the frequency of prescriptions written and in terms of the total value of requested NHI reimbursements.As a result we found the following information on the drugs studies : the products were sold through a direct sales route that did not involve a wholesaler, package inserts were less revised than the original drugs, IFs were not provided or, if they were, the contents were not sufficient (often not even easily obtainable data or references), the smallest unit provided were larger than the original drugs', and the manufacturers of generic equivalents did not have branch offices in the same prefecture as our hospital.The product quality of the drugs remains a very important factor. However, in addition to the price, a stable source of supply for all drugs from which prompt delivery of the drug itself, as well as adequate product information are needed to ensure the safe and appropriate use of the products. As a result of the above investigations, the overall growth of the Generic Drug Market is expected to increase in the near future.