Bristol-Myers Squibb Company and sanofi-aventis announced that the United States Food and Drug Administration (FDA) has granted the companies an additional six-month period of exclusivity to market Plavix (clopidogrel bisulfate). Exclusivity for Plavix in the US is now scheduled to expire on May 17, 2012.

Plavix is marketed by Bristol-Myers Squibb and sanofi-aventis, and is indicated for adult patients as follows: Acute Coronary Syndrome patients with non-ST-segment elevation ACS [unstable angina (UA)/Non-ST-Elevation Myocardial Infarction (NSTEMI)], including patients who are to be managed medically and those who are to be managed with coronary revascularization, Plavix has been shown to decrease the rate of a combined endpoint of cardiovascular death, Myocardial Infarction (MI), or stroke as well as the rate of a combined endpoint of cardiovascular death, MI, stroke, or refractory ischemia.

For patients with ST-Elevation Myocardial Infarction (STEMI), Plavix has been shown to reduce the rate of death from any cause and the rate of a combined endpoint of death, re-infarction, or stroke. The benefit for patients who undergo primary percutaneous coronary intervention is unknown. The optimal duration of Plavix therapy in ACS is unknown.

For patients with a history of recent Myocardial Infarction (MI), recent stroke, or established peripheral arterial disease, Plavix has been shown to reduce the rate of a combined endpoint of new ischemic stroke (fatal or not), new MI (fatal or not), and other vascular death.

The effectiveness of Plavix is dependent on its activation to an active metabolite by the cytochrome P450 (CYP) system, principally CYP2C19. Plavix at recommended doses forms less of that metabolite and has a smaller effect on platelet function in patients who are CYP2C19 poor metabolizers. Poor metabolizers with acute coronary syndrome or undergoing percutaneous coronary intervention treated with Plavix at recommended doses exhibit higher cardiovascular event rates than do patients with normal CYP2C19 function. Tests are available to identify a patient's CYP2C19 genotype; these tests can be used as an aid in determining therapeutic strategy. Consider alternative treatment or treatment strategies in patients identified as CYP2C19 poor metabolizers.

Plavix is contraindicated in patients with active pathological bleeding such as peptic ulcer or intracranial haemorrhage, with hypersensitivity (e.g., anaphylaxis) to clopidogrel or any component of the product.

Avoid concomitant use of Plavix and drugs that inhibit CYP2C19 activity. Co-administration of Plavix with omeprazole, a proton pump inhibitor that is an inhibitor of CYP2C19, reduces the pharmacological activity of Plavix if given concomitantly or if given 12 hours apart. Consider using another acid-reducing agent with less CYP2C19 inhibitory activity. Pantoprazole, a weak CYP2C19 inhibitor, had less effect on the pharmacologicalactivity of Plavix (clopidogrel bisulfate) than omeprazole.

Thienopyridines, including Plavix, increase the risk of bleeding. If a patient is to undergo surgery and an anti-platelet effect is not desired, discontinue Plavix 5 days prior to surgery. Avoid lapses in therapy, and if Plavix must be temporarily discontinued, restart as soon as possible. Premature discontinuation of Plavix may increase the risk of cardiovascular events.

In patients with recent TIA or stroke who are at high risk for recurrent ischemic events, the combination of aspirin and Plavix has not been shown to be more effective than Plavix alone, but the combination has been shown to increase major bleeding.

TTP, sometimes fatal, has been reported following use of Plavix, sometimes after a short exposure (<2 weeks). TTP is a serious condition that requires urgent treatment including plasmapheresis (plasma exchange). Bleeding, including life-threatening and fatal bleeding, is the most commonly adverse reactions.

Co-administering warfarin with Plavix increases the risk of bleeding. Co-administration of Plavix and NSAIDs increases the risk of gastrointestinal bleeding. Discontinue drug or nursing, taking into consideration importance of drug to mother.

Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases.

Sanofi-aventis, a leading global pharmaceutical company, discovers, develops and distributes therapeutic solutions to improve the lives of everyone.