IMPORTANT SAFETY INFORMATION
The effectiveness of PLAVIX is dependent on its activation to an active metabolite by the cytochrome P450
(CYP) system, principally CYP2C19 [See Warnings and Precautions (5.1)]. 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 [See Clinical Pharmacology (12.5)]. Consider
alternative treatment or treatment strategies in patients identified as CYP2C19 poor metabolizers
[See Dosage and Administration (2.3)].
PLAVIX is contraindicated in patients with active pathological bleeding such as peptic ulcer or intracranial hemorrhage.
PLAVIX is contraindicated in patients with hypersensitivity (e.g., anaphylaxis) to clopidogrel or any component of the
product.
Avoid concomitant use of PLAVIX and strong or moderate CYP2C19 inhibitors. Omeprazole, a moderate CYP2C19
inhibitor, has been shown to reduce 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 pharmacological activity of PLAVIX than omeprazole [See Drug Interactions (7.1) and
Dosage and Administration (2.4)].
Thienopyridines, including PLAVIX, increase the risk of bleeding. If a patient is to undergo surgery and an antiplatelet
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 reported adverse reaction.
Coadministering warfarin with PLAVIX increases the risk of bleeding.
Coadministration of PLAVIX and NSAIDs increases the risk of gastrointestinal bleeding.
Nursing mothers: Discontinue drug or nursing, taking into consideration importance of drug to mother.
INDICATIONS
For 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.
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