Prasugrel approved by the FDA

July 10 by C. Michael Gibson, M.S., M.D. (click here for Dr. Gibson's disclosures)

The Food and Drug Administration announced today that Prasugrel (which will be sold under the name Effient) is now approved for clinical use. The drug's label indicates that the drug is effective in reducing the risk of stroke and heart attack in patients undergoing percutaneous coronary intervention and will carry a black label warning regarding an increased risk of potentially fatal bleeding. A panel convened by the FDA had previously voted 9-0 in a recommendation for approval on February 3^rd, 2009.

The FDA's Director of New Drugs, John Jenkins, stated in a press release that "Effient offers physicians an alternative treatment for preventing dangerous blood clots from forming and causing a heart attack or stroke during or after an angioplasty procedure," and that "physicians must carefully weigh the potential benefits and risks of Effient as they decide which patients should receive the drug." Click File:Effient.pdf to download a pdf of Prasugrel's package insert.

FDA statement also indicated that Prasugrel should be avoided in patients with ongoing, a history of stroke or transient ischemic attacks (TIAs or small temporary-strokes), or an urgent need for surgery, including CABG (coronary artery bypass graft surgery). A press release from Eli Lilly and Daiichi-Sankyo stated that "Effient is contraindicated in patients with a history of prior TIA/stroke. It is generally not recommended in patients 75 years of age or older, except for patients in high-risk situations, such as those with diabetes or a history of prior heart attack."

Given the potential risk of bleeding, it is notable that there are two approved maintenance doses of Prasugrel: 10 mg which was studied in the Triton TIMI 38 trial, and a reduced dose of 5 mg that may be more suitable in patients at an increased risk of bleeding including those patients who weigh less than 60 Kg (132 pounds).

The manufacturese of the drug also stated the following in the press release:

"Antiplatelet medicines, including Effient, can increase the risk of bleeding. If patients have unexplained or excessive bleeding while on Effient, they should contact their doctor right away as some bleeding can be serious, and sometimes may lead to death. Patients should not take Effient if they have a stomach ulcer or other conditions that cause bleeding or if they have a history of stroke or “mini-stroke” (transient ischemic attack or TIA)."

"If patients are 75 or older, or if they weigh less than 132 pounds, or if they are taking anticoagulants (eg, warfarin) or taking NSAIDs (eg, ibuprofen or naproxen) for a long time, they should talk to their doctor, as they may be at an increased risk of bleeding."

"If patients plan to have surgery or a dental procedure, they should tell their doctors that they are taking Effient."

"Patients should not stop taking Effient without first talking to the doctor who prescribed it for them, as this may result in increased risk of a clot in their stent, a heart attack or death."

"Patients should get medical attention right away if they develop any of the following unexpected symptoms: fever, weakness, yellowing of the skin or eyes, or if skin becomes very pale or dotted with purple spots. These symptoms may be signs of a rare but potentially life-threatening condition called TTP, which has been reported with other medicines in this class."

Although concerns had been expressed regarding an excess risk of cancer in the Prasugrel arm, Deputy Director of the Cardiovascular & Renal Products division, Ellis Unger, stated that there is no increase in the relative risk of cancer for prasugrel over clopidogrel if those patients with gastrointestinal bleeding are excluded from the analysis.

The drug is marketed by both Eli Lilly and Daiichi-Sankyo.