Bioequivalence and Bioavailability Forum

Dear all
Exemestane absorption is significantly affected by concomitant ingestion of food. Concomitant intake with food increases the bioavailability by 40%.

Section 3.2.2 of the old BE Guideline states that if the SPC of the reference product contains specific recommendations in relation to food intake related to food interaction the study should be designed accordingly. According to the Questions & Answers on the Bioavailability and Bioequivalence Guideline (EMEA/CHMP/EWP/40326/2006) the recommendations concerning food intake in the SPC are not sufficient for regulatory decisions on the adequacy of bioequivalence studies. It is pointed out in this document that if the recommendation of food intake in the SPC is based on pharmacokinetic properties such as higher bioavailability, then a bioequivalence study under fed conditions is generally required.

Unfortunately it is a weakness of the originator's SPC to state that exemestane tablets are to be taken "once daily preferably after a meal" keeping in mind the decreased bioavailability when administered in the fasted state. Ingestion of the drug under fasting conditions may result in plasma levels below the minimum effective concentrations, which is an unfortunate situation for patients and could be discussed as a potential serious risk to public health. Since all Phase III studies were performed in the fed state the efficacy of exemestane 25 mg given in the fasted state is not proven. The FDA approved PIL therefore clearly states "Take your dose of AROMASIN once a day, every day, after a meal."

I know that with the next revision of the European SPCs and PILs the text will be adapted in that way that Aromasin (or any other exemestane formulation) has to be taken with a meal. Several regulatory authorities accepted the argumentation given above.

If you have any question please contact me.
Kind regards
Dan