Questions and answers on Ethanol in the context of the revision of the guideline on 'Excipients in the label and package leaflet of medicinal products for human use'(CPMP/463/00)

About this guideline

End of consultation (overseas): 31 May 2014

Note: Annex only (pp 13-14)

Categories: Clinical efficacy and safety | General (clinical)

TGA annotations

The Annex to the European Medicines Agency's (EMA) draft Questions and Answers on Ethanol in the context of the revision of the guideline on 'Excipients in the label and package leaflet of medicinal products for human use' (CPMP/463/00) provides guidance on ethanol intake, predicted rise in Blood Alcohol Concentration (BAC), and suggested limits when used as an excipient in medicines. This Annex should be used by sponsors to inform dosage instructions for different age groups, which can be calculated using average weights for each group. The TGA is not adopting the required warning statements included in the EMA's Q&A document. Recommendations for limits on exposure to ethanol are intended to avoid exceeding a predicted rise in BAC of 0.01 g/L for patients 2-6 years old, and 0.125 g/L for patients 6 years old and over, because of the following risks, which are particularly relevant to children:

• ingestion of acute doses (risk of mortality & toxicity)
• cumulative effects from long-term exposure that occurs during therapy for chronic conditions/long term use
• alcohol exposure during brain development
• mis-dosing or overdosing of alcohol-containing medicines in children, particularly from those containing high concentration of alcohol.

The TGA agrees that sponsors should also give consideration to the following points noted in the EMA's Q&A document:

• Ethanol should not be used in medicinal products unless justified
• The total volume of ethanol in any medicinal product should be adapted in such a way that a potentially lethal dose of 1.8 g/kg (corresponds to a predicted rise in BAC of 3 g/L) cannot be reached in the event of accidental poisoning in children involving the entire package.

For more information see International scientific guidelines adopted in Australia.