Why must prasugrel (Effient) be stored in the original bottle?

Prasugrel (Effient) is a new platelet inhibitor manufactured by Eli Lilly. During the review process by the FDA it was discovered that the base form of the medication was not as well absorbed by patients on proton-pump inhibitors or H2 antagonists (both increase the gastric PH). So the company developed a salt form of the medication prasugrel HCL which is better absorbed at high PH.

In addition, the company discovered during the quality control process of their manufacturing that a reaction occurs (strongly correlated with temperature and high humidity) that drug degrades from the salt form to the base form. Analysis was completed it was found that the Cmax is delayed, when the base form is administered in patients with high PH, which theoretically could have clinical significance as it delays the time of maximal platelet inhibition. No clinical significance of the conversion from salt to base was described in analysis submitted to the FDA in terms of outcomes from the clinical trials. Even in situations of high conversion to the base, and high PH, the pharmacodynamic effects of prasugrel were superior to clopidogrel.

This type of manufacturing quality control examination has not occurred with all medications and the extent of conversion from salt to base forms for other medications is unknown. The company has packed the medication to minimize the potential impact of the conversion of salt to base by recommending storage in the original bottle and the addition of a desiccant to control humidity.

It is currently available as 5mg tablets (bottles of 7 and 30) and 10mg tablets (bottles of 30 and unit-dose blisters 90). This leads to challenges for hospitals that dispense medications in unit-dose tablets as the 5mg tablets are not available in a unit-dose formulation. This has implications for patient safety as the manufacturer currently recommends against repackaging their product. Pharmacists are awaiting the release of a 5mg unit dose product or clarification from the company about repackaging.