Common Questions About PLAVIX


Find the answers to frequent PLAVIX questions, along with additional PLAVIX information.

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 PLAVIX doses.1

When does inhibition of platelet aggregation by PLAVIX reach a steady state?

Repeated doses of PLAVIX 75 mg 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 PLAVIX 75 mg per day was between 40% and 60%.1

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 (including insulin), thrombolytics, heparins (unfractionated and LMWH) GPIIb/IIIa antagonists, antiepileptic agents and hormone replacement therapy without evidence of clinically significant adverse interactions.1

Is bleeding time increased with PLAVIX?

Yes, the use of 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.1

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?

PLAVIX contraindications are 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?

PLAVIX long-term use is described in the CAPRIE Trial. 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.1 Over the 3-year follow-up period, PLAVIX was found to reduce the risk of the combined end point of MI, ischemic stroke, or vascular death, compared to aspirin.1
Learn more about the CAPRIE Trial.

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).1
Learn more about the CURE Trial.

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 81,000 patients, including over 31,000 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 cerebral bleeding in COMMIT was low and similar in both groups.

Learn more about PLAVIX Safety and Side Effects

What is TTP (thrombotic thrombocytopenic purpura)?

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.1

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.1

Important Risk Information

PLAVIX is contraindicated in patients with active pathologic bleeding such as peptic ulcer or intracranial hemorrhage. PLAVIX should be used with caution in patients who may be at risk of increased bleeding from trauma, surgery, or coadministration with NSAIDs or warfarin. (See CONTRAINDICATIONS and PRECAUTIONS.*)

The metabolism of PLAVIX can be impaired by genetic variations in CYP2C19 and by concomitant medications that interfere with CYP2C19 (eg,omeprazole), causing reduced effectiveness. Avoid use of PLAVIX in patients with impaired CYP2C19 function due to known genetic variation or due to drugs that inhibit CYP2C19 activity. (See WARNINGS and PRECAUTIONS: Drug Interactions.*)

As part of the worldwide postmarketing experience with PLAVIX, there have been cases of reported thrombotic thrombocytopenic purpura (TTP), some with fatal outcome. 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). (See WARNINGS.*)

The rates of major and minor bleeding were higher in patients treated with PLAVIX plus aspirin compared with placebo plus aspirin in clinical trials. (See ADVERSE REACTIONS.*)

In clinical trials, the most common clinically important side effects were pruritus, purpura, diarrhea, and rash; infrequent events included intracranial hemorrhage (0.4%) and severe neutropenia (0.05%). (See ADVERSE REACTIONS.*)

*Please See the Full PLAVIX Prescribing Information

PLAVIX Indications

PLAVIX® (clopidigrel bisulfate) is indicated for the reduction of atherothrombotic events as follows:

–
Use PLAVIX plus aspirin for patients with non-ST-segment elevation acute coronary syndrome (UA/non-Q-wave MI), including patients to be managed medically and those to be managed with percutaneous coronary intervention (with or without stent) or CABG, to decrease the rate of a combined end point of CV death, MI, or stroke as well as the rate of a combined end point of CV death, MI, stroke, or refractory ischemia.

–
Use PLAVIX plus aspirin for patients with ST-segment elevation acute myocardial infarction to reduce the rate of death from any cause and the rate of a combined end point of death, reinfarction, or stroke. This benefit is not known to pertain to patients who receive primary angioplasty.

–
Use PLAVIX alone for patients with a history of recent stroke, recent MI, or established PAD to reduce the rate of a combined end point of new ischemic stroke (fatal or not), new MI (fatal or not), and other vascular death.