Release of levetiracetam from extended-release tablets that appear intact in patient stool

Many antiepileptic drugs (AEDs) are extended-release (ER) tablets, such that an entire day’s dose is taken only once or twice daily. A patient taking four levetiracetam ER 500 mg tablets twice daily was alarmed when, after switching from a generic manufactured by Sun to a generic manufactured by Lupin, ER tablet remnants appeared as intact tablets in his stool, suggesting no drug was absorbed. Since Sun tablets were no longer available from the pharmacy, the patient was switched to a third manufacturer (i.e. Apotex), resulting in no intact remnant tablets in the stool. We analyzed the recovered Lupin tablets from stool and measured patient drug level to assess whether drug was released from the tablets. The patient provided five remnant tablets (Lupin; Lot G409239) from two bowel movements over a 24 h period. These remnants, as well as unused tablets from his prescription bottle, brand-name