Minutes of the 5th Safety Measures Investigation Council Meeting, FY2026
Overview
At its meeting on July 29, 2026, the Safety Measures Investigation Council deliberated on revising the Precautions for Use for olanzapine and changing the risk classification of over-the-counter loxoprofen. The council agreed to lift the contraindication for patients with diabetes and others only when olanzapine is used for chemotherapy-induced nausea and vomiting (CINV), subject to conditions such as blood glucose management, and to instruct the marketing authorization holder to revise the labeling. It also agreed in principle to reclassify loxoprofen as a Designated Class 2 OTC medicine, subject to measures including explanations at the point of sale, training, caution labeling, and surveys of actual use. The council will proceed to organize the specific conditions and conduct a public comment process.
Key points
- The council approved a package insert revision lifting the contraindication for patients with diabetes and others only when olanzapine is used for CINV.
- The council approved in principle the move of loxoprofen to Designated Class 2 OTC medicine, subject to multiple conditions.
- The specific conditions for loxoprofen will be documented, followed by public comments and deliberation by the Safety Measures Committee.
Overview
The council meeting was held on July 29, 2026. It was open to the public via a live YouTube stream, and attendees were told that the minutes would later be posted on the Ministry of Health, Labour and Welfare website.
The agenda covered revision of the Precautions for Use for olanzapine and the risk classification of OTC medicines. All 6 committee members attended, meeting the quorum requirement.
Following recognition that some products had not had their risk classifications reconsidered for many years, a system was established to periodically review whether OTC medicines should be reclassified. Requests have been accepted since April 1, 2026. This meeting considered a request concerning loxoprofen.
Impact
The expert stated that restricting patients with diabetes to a three-drug combination regimen without olanzapine could mean they experience more severe nausea and vomiting than patients without diabetes, raising concerns about patient distress and adverse effects on prognosis.
According to the expert, without antiemetics, more than 90% of patients vomit during highly emetogenic chemotherapy, while the complete vomiting suppression rate for the conventional three-drug combination regimen was about 60%. A four-drug regimen including olanzapine showed a suppression rate of 85–90% in domestic trials.
The expert reported that in a Phase III trial, the complete suppression rate for delayed-phase vomiting was 79% in the olanzapine group and 66% in the placebo group in the cisplatin trial; in the breast cancer AC therapy trial, the rates were 58% and 36%, respectively.
Details
The scope is limited to oral olanzapine used for CINV. Administration to patients with diabetes and others is subject to managing patients with well-controlled blood glucose in hospital, conducting frequent daily blood glucose measurements before and during treatment, confirming stable blood glucose using the most recent blood test on the day of discharge, and maintaining an emergency response system. Materials for patients and families on symptoms after discharge, provision of blood glucose monitoring information to medical institutions, and a safety survey are also planned.
Olanzapine was approved for schizophrenia in December 2000, and patients with diabetes and others became contraindicated in April 2002 following an urgent safety notice. The CINV indication was added in February 2017, but the scope of the contraindication remained unchanged. Following the council's agreement, the marketing authorization holder will be instructed to revise the Precautions for Use.
Oral loxoprofen was designated a Class 1 OTC medicine on January 22, 2015. The current request seeks reclassification to Designated Class 2. The council had previously opined that there was no reason to treat it more strictly than similar drugs; however, the background to the committee's Class 1 designation, including shipment volume, household stocking, and risks in late pregnancy, was explained.
The submitted materials stated that the adverse reaction incidence rate over the most recent 3 years was not higher than in the survey at the time of designation, and that serious adverse reactions after designation occurred at a single-digit level each year. Of 63 cases after designation, 8 involved unknown adverse reactions; there were 8 unknown and serious adverse reaction reports, and causality could not be assessed for the 1 case resulting in death. A comparison of serious adverse reactions for similar drugs from 2011 to 2025 covered 77 loxoprofen cases, 127 aspirin cases, and 421 ibuprofen cases.
In a proper-use survey conducted in May–June 2026, the rate of inappropriate use regarding the number of tablets per dose was 5.9%. For the continuous-use period, normally set at 3–5 days, use for 6 days or more was 5.1%. The rate of applicable cases during pregnancy or late pregnancy was 0%. The company said it would emphasize cautions about the number of tablets and duration of use, and continue warnings regarding late pregnancy.
Potential conditions for reclassification included requiring the marketing authorization holder to provide caution labels on dosage, duration, and duplicate ingredients; provide training materials and checklists; and conduct surveys on adverse reactions and proper use. Sellers would be required to train registered sellers, explain and confirm use at the point of sale, inform customers about early symptoms of serious adverse reactions and how to report them, and coordinate with pharmacists as needed. The council approved in principle designating loxoprofen as Class 2 once these conditions have been documented.