Q（Question）

With respect to principle ①, is it permissible to present data such as increased adverse events or diminished efficacy when the drug is administered at unapproved dosages, for the purpose of issuing safety alerts?

A（MHLW answer）

If the information is necessary for the safe use of the drug and the purpose is to issue a safety alert, it may be provided. However, care must be taken to ensure that the purpose does not become one of recommending off-label use, such as showing that administration at unapproved dosages posed no efficacy or safety concerns.

So what (meaning): Safety alerts presenting risks (increased adverse events, reduced efficacy) associated with off-label dosing are permissible. Sharing data that shows off-label dosing had no problems — effectively endorsing unapproved use — is not.

So why (rationale): Safety information is essential for patient protection; however, presenting favorable outcomes for off-label use constitutes indirect promotion of unapproved use, so a clear distinction based on the purpose of the information is required.

Commentary — background, application, practical notes

Providing safety information is an essential activity for ensuring the appropriate use of drugs and protecting patients, and this naturally includes risk information associated with off-label dosages and administration methods. What this Q&A confirms is a judgment standard centered on 'whether the purpose is to issue a safety alert,' looking not only at the content of the information itself but also at whether the context, intent, and manner of its delivery function as a risk warning.

A typical permissible scenario is informing a physician that adverse event rates increase when the drug is administered at doses exceeding the approved level, framed in a context that encourages adherence to the labeled dosage. Explicitly presenting the risks of off-label dosing is properly characterized as a safety alert that supports appropriate prescribing practice.

The prohibited side of the boundary is presenting data showing that administration at off-label dosages 'raised no efficacy or safety concerns.' This is not a safety alert but an affirmation and implicit recommendation of off-label use; even when presented in the form of 'providing information,' it violates the Guidelines. Data that characterizes off-label dosing as presenting no problems is prohibited regardless of the stated purpose of the provision.