Q&A
How soon does inhibition of platelet aggregation occur after starting treatment with PLAVIX (clopidogrel bisulfate)?
Dose-dependent inhibition of platelet aggregation can be seen 2 hours after single oral doses of PLAVIX.
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When does inhibition of platelet aggregation by PLAVIX reach a steady state?
Repeated doses of 75 mg PLAVIX per day inhibit ADP-induced platelet aggregation on the first day, and inhibition of platelet aggregation by PLAVIX reaches steady state between Day 3 and Day 7. At steady state, the average inhibition level observed with a dose of 75 mg PLAVIX per day was between 40% and 60%.
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Can PLAVIX be taken along with other standard cardiovascular therapies?
Patients in clinical trials with PLAVIX received a variety of concomitant medications including diuretics, beta-blocking agents, angiotensin converting enzyme (ACE) inhibitors, calcium antagonists, cholesterol-lowering agents, coronary vasodilators, antidiabetic agents (includ ing insulin), thrombolytics, heparins (unfractionated and LMWH) GPIIb/IIIa antagonists, antiepileptic agents and hormone replacement therapy without evidence of clinically significant adverse interactions.
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Is bleeding time increased with PLAVIX?
Yes, PLAVIX prolongs the bleeding time and therefore should be used with caution in patients who may be at risk of increased bleeding from trauma, surgery, or other pathological conditions (particularly gastrointestinal and intraocular). If a patient is to undergo elective surgery and an antiplatelet effect is not desired, PLAVIX should be discontinued 5 days prior to surgery.
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Due to the risk of bleeding and undesirable hematological effects, blood cell count determination and/or other appropriate testing should be promptly considered, whenever such suspected clinical symptoms arise during the course of treatment.
In patients with recent transient ischemic attack (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.
In which patients is PLAVIX contraindicated?
The use of PLAVIX is contraindicated in the following conditions: Hypersensitivity to the drug substance or any component of the product. Active pathological bleeding such as peptic ulcer or intracranial hemorrhage.
Is PLAVIX effective in long-term reduction of the risk of atherothrombotic events?
CAPRIE compared PLAVIX to aspirin in patients with recent myocardial infarction (MI), recent ischemic stroke, or established peripheral arterial disease (PAD), for up to 3 years. Over the 3-year follow-up period, PLAVIX was found to reduce the risk of the combined end point of MI, ischemic stroke, and vascular death, compared to aspirin.
PLAVIX with aspirin was studied as part of the CURE trial. CURE studied patients with acute coronary syndrome (ACS) with unstable angina or non-Q wave MI, for up to 1 year. After 1 year, PLAVIX was found to reduce the risk of the combined end point of cardiovascular death, MI, stroke, or refractory ischemia, compared to placebo. The benefits of PLAVIX were maintained throughout the course of the CURE trial (for up to 1 year).
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How often does PLAVIX have to be administered?
Recent MI, Recent Stroke, or Established Peripheral Arterial Disease
The recommended daily dose of PLAVIX is 75 mg once daily.
Acute Coronary Syndrome
For patients with non-ST-segment elevation acute coronary syndrome (unstable angina/non-Q-wave MI), PLAVIX should be initiated with a single 300-mg loading dose and then continued at 75 mg once daily. Aspirin (75 mg-325 mg once daily) should be initiated and continued in combination with PLAVIX. In CURE, most patients with Acute Coronary Syndrome also received heparin acutely.
For patients with ST-segment elevation acute myocardial infarction, the recommended dose of PLAVIX is 75 mg once daily, administered in combination with aspirin, with or without thrombolytics. PLAVIX may be initiated with or without a loading dose (300 mg was used in CLARITY).
PLAVIX can be administered with or without food.
No dosage adjustment is necessary for elderly patients or patients with renal disease.
What adverse reactions are associated with PLAVIX?
PLAVIX has been evaluated for safety in more than 42,000 patients, including over 81,000 patients treated for 1 year or more. The clinically important adverse events observed in CAPRIE, CURE, CLARITY and COMMIT are discussed below.
The overall tolerability of PLAVIX in CAPRIE was similar to that of aspirin regardless of age, gender and race, with an approximately equal incidence (13%) of patients withdrawing from treatment because of adverse reactions.
Hemorrhagic: In CAPRIE patients receiving PLAVIX, gastrointestinal hemorrhage occurred at a rate of 2.0%, and required hospitalization in 0.7%. In patients receiving aspirin, the corresponding rates were 2.7% and 1.1%, respectively. The incidence of intracranial hemorrhage was 0.4% for PLAVIX compared to 0.5% for aspirin.
In CURE, PLAVIX use with aspirin was associated with an increase in bleeding compared to placebo with aspirin. There was an excess in major bleeding in patients receiving PLAVIX plus aspirin compared with placebo plus aspirin, primarily gastrointestinal and at puncture sites. The incidence of intracranial hemorrhage (0.1%), and fatal bleeding (0.2%), were the same in both groups.
Ninety-two percent (92%) of the patients in the CURE study received heparin/LMWH, and the rate of bleeding in these patients was similar to the overall results.
There was no excess in major bleeds within seven days after coronary bypass graft surgery in patients who stopped therapy more than five days prior to surgery (event rate 4.4% PLAVIX + aspirin; 5.3% placebo + aspirin). In patients who remained on therapy within five days of bypass graft surgery, the event rate was 9.6% for PLAVIX + aspirin, and 6.3% for placebo + aspirin.
In CLARITY, the incidence of major bleeding (defined as intracranial bleeding or bleeding associated with a fall in hemoglobin > 5 g/dL) was similar between groups (1.3% versus 1.1% in the PLAVIX + aspirin and in the placebo + aspirin groups, respectively). This was consistent across subgroups of patients defined by baseline characteristics, and type of fibrinolytics or heparin therapy. The incidence of fatal bleeding (0.8% versus 0.6% in the PLAVIX + aspirin and in the placebo + aspirin groups, respectively) and intracranial hemorrhage (0.5% versus 0.7%, respectively) was low and similar in both groups.
The overall rate of noncerebral major bleeding or cerebal bleeding (Plavix plus Aspirin: 0.6% vs. Placebo plus Aspirin: 0.5%) in COMMIT was low and similar in both groups.
What is thrombotic thrombocytopenic purpura (TTP)?
TTP has been reported rarely following use of PLAVIX, sometimes after a short exposure (<2 weeks). TTP is a serious condition that can be fatal and requires urgent treatment including plasmapheresis (plasma exchange). It is characterized by thrombocytopenia, microangiopathic hemolytic anemia (schistocytes [fragmented RBCs] seen on peripheral smear), neurological findings, renal dysfunction, and fever.
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What should patients know about taking PLAVIX?
Patients should be told that it may take them longer than usual to stop bleeding, that they may bruise and/or bleed more easily when they take PLAVIX or PLAVIX combined with aspirin, and that they should report any unusual bleeding to their physician. Patients should inform physicians and dentists that they are taking PLAVIX and/or any other product known to affect bleeding before any surgery is scheduled and before any new drug is taken.
Should PLAVIX be discontinued prior to surgery?
PLAVIX prolongs the bleeding time and therefore should be used with caution in patients who may be at risk of increased bleeding from trauma, surgery, or other pathological conditions (particularly gastrointestinal and intraocular). If a patient is to undergo elective surgery and an antiplatelet effect is not desired, PLAVIX should be discontinued 5 days prior to surgery.
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