PLAVIX has a well-established safety profile in a broad range of patients
A proven safety profile studied
- In the acute care setting4
- In ACS (unstable angina (UA)/non-ST-segment elevation MI (NSTEMI)) patients with or without a stent4
- In combination with aspirin in ACS patients1
- Long term as monotherapy up to 3 years — similar safety and tolerability to aspirin 325 mg1,3
- In combination with aspirin in ACS patients (UA/NSTEMI) — major bleeding rates were higher and dose dependent on aspirin1
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.
PLAVIX Side Effects:
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%).
Learn more about PLAVIX side effects and safety in each of these clinical trials
- CAPRIE Trial
Similar safety and tolerability to aspirin 325 mg, including intracranial hemorrhage (0.4% for PLAVIX, 0.5% for aspirin) and GI bleeding (2.0% for PLAVIX, 2.7% for aspirin).1
Learn more about safety in the CAPRIE Trial.
- COMMIT Trial
Overall rate of major bleeding was low and similar in both groups (0.6% for PLAVIX + aspirin, 0.5% for placebo + aspirin).1
Learn more about safety in the COMMIT Trial.
- CLARITY Trial - a bridging trial to COMMIT
Incidence of fatal bleeding (0.8% for PLAVIX + aspirin, 0.6% for placebo + aspirin) and intracranial hemorrhage (0.5% for PLAVIX + aspirin, 0.7% for placebo + aspirin) was low and similar in both groups.1
Learn more about safety in the CLARITY Trial.
CAPRIE Trial: PLAVIX side effects included similar bleeding and adverse event rates to
Aspirin 325 mg
PLAVIX in recent MI, recent ischemic
stroke, or established PAD |
% Incidence |
| CAPRIE–Bleeding* up to 3 years1, 3 |
PLAVIX 75 mg
n=9,599 |
Aspirin 325 mg
n=9,586 |
| Intracranial hemorrhage |
0.4 |
0.5 |
| GI bleeding |
2.0 |
2.7 |
| Hospitalization due to GI hemorrhage |
0.7 |
1.1 |
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.
*Other bleeding events that were reported more frequently in the PLAVIX group were epistaxis and hematoma.
Tolerability13
Selected adverse events occurring in ≥2.5% of PLAVIX patients with discontinuation rates ≥0.2%
|
% Incidence (% Discontinuance) |
|
PLAVIX 75 mg
n=9,599 |
Aspirin 325 mg
n=9,586 |
| Chest pain |
8.3 (0.2) |
8.3 (0.3) |
| Headache |
7.6 (0.3) |
7.2 (0.2) |
| Dizziness |
6.2 (0.2) |
6.7 (0.3) |
| GI system disorders–Any event |
27.1 (3.2) |
29.8 (4.0) |
| Abdominal pain |
5.6 (0.7) |
5.2 (0.6) |
| Dyspepsia |
5.2 (0.6) |
6.1 (0.7) |
| Diarrhea |
4.5 (0.4) |
3.4 (0.3) |
| Nausea |
3.4 (0.5) |
3.8 (0.4) |
| Pupura/Bruise |
5.3 (0.3) |
3.7 (0.1) |
| Epistaxis |
2.9 (0.2) |
2.5 (0.1) |
| Skin & appendage disorders–Any event |
15.8 (1.5) |
13.1 (0.8) |
| Rash |
4.2 (0.5) |
3.5 (0.2) |
| Pruritus |
3.3 (0.3) |
1.6 (0.1) |
The effectiveness of Plavix depends on activation to an active metabolite by the cytochrome P450 (CYP) system, principally CYP2C19. Poor metabolizers treated with Plavix at recommended doses exhibit higher cardiovascular event rates following acute coronary syndrome (ACS) or percutaneous coronary intervention (PCI) than patients with normal CYP2C19 function. Consider alternative treatment or treatment strategies in patients identified as CYP2C19 poor metabolizers (See Full Prescribing Information for Complete BOXED WARNING).
In CAPRIE, which compared PLAVIX with aspirin, pruritus was more frequently reported in those taking PLAVIX. No other difference in the rate of adverse events (other than bleeding) was reported.
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).1
Learn more about the CAPRIE Trial
CURE Trial: Bleeding Rates Determined by Aspirin Dose1
In the CURE Trial of 12,562 UA/NSTEMI Patients, the Rates of Major and Minor Bleeding Were Higher in patients treated with PLAVIX + Aspirin compared with Placebo + Aspirin1
| PLAVIX + aspirin in UA/NSTEMI |
% Incidence |
| CURE–up to 1 year1 |
PLAVIX + aspirin
n=6,259 |
Placebo + aspirin
n=6,303 |
P-value |
| Major bleeding* |
3.7 |
2.7 |
0.001 |
| Life-threatening |
2.2 |
1.8 |
0.13 |
| Fatal |
0.2 |
0.2 |
|
| 5 g/dL hemoglobin drop |
0.9 |
0.9 |
|
| Requiring surgical intervention |
0.7 |
0.7 |
|
| Hemorrhagic strokes |
0.1 |
0.1 |
|
| Requiring inotropes |
0.5 |
0.5 |
|
| Requiring transfusion (≥4 units) |
1.2 |
1.0 |
|
| Other major bleeding |
1.6 |
1.0 |
0.005 |
| Significantly disabling |
0.4 |
0.3 |
|
Intraocular bleeding with significant
loss of vision |
0.05 |
0.03 |
|
| Requiring 2-3 units of blood |
1.3 |
0.9 |
|
| Minor bleeding |
5.1 |
2.4 |
<0.001 |
*Major bleeding and other life-threatening bleeding1
Major bleeding rates were DOSE DEPENDENT on aspirin
| Major bleeding by aspirin dose |
% Incidence |
| Aspirin dose |
PLAVIX + aspirin |
Placebo + aspirin |
| <100 mg |
2.6 |
2.0 |
| 100-200 mg |
3.5 |
2.3 |
| >200 mg |
4.9 |
4.0 |
Learn more about the CURE Trial
COMMIT Trial
In the COMMIT Trial of 45,852 STEMI Patients, the overall rate of non-cerebral major bleeding or cerebral bleeding was low and similar in both groups1
| PLAVIX + aspirin in STEMI |
% Incidence |
COMMIT–until hospital discharge or
up to 28 days1 |
PLAVIX + aspirin
n=22,961 |
Placebo + aspirin
n=22,891 |
P-value |
| Major bleeding* |
0.6 |
0.5 |
0.59 |
| Major non-cerebral bleeding |
0.4 |
0.3 |
0.48 |
| Fatal non-cerebral bleeding |
0.2 |
0.2 |
0.90 |
| Hemorrhagic stroke |
0.2 |
0.2 |
0.91 |
| Fatal hemorrhagic stroke |
0.2 |
0.2 |
0.81 |
| Other non-cerebral bleeding (nonmajor) |
3.6 |
3.1 |
0.005 |
| Any non-cerebral bleeding |
3.9 |
3.4 |
0.004 |
*Major bleeding rates were cerebral bleeds or non-cerebral bleeds thought to have caused death or that required transfusion.
In the COMMIT Trial, 11,934 patients were ≥70 years old6
The relative rate of major non-cerebral or cerebral bleeding was independent of age (event rates by age for PLAVIX + aspirin vs. placebo + aspirin: <60=0.3% vs. 0.4%; ≥60 to <70=0.7% vs. 0.6%; ≥70=0.8% vs. 0.7%
Learn more about the COMMIT Trial
CLARITY Trial - a bridging trial to COMMIT, which supports a 300 mg PLAVIX loading dose in a STEMI patient population
In the CLARITY trial of 3,491 STEMI patients, the incidence of fatal bleeding and intracranial hemorrhage was low and similar in both groups1,7
| PLAVIX + aspirin in STEMI |
% Incidence |
CLARITY–until angiography,
discharge, or day 85,7* |
PLAVIX + aspirin
n=1,733 |
Placebo + aspirin
n=1,719 |
TIMI major bleeding through day
after angiography† |
1.3 |
1.1 |
| Intracranial hemorrhage |
0.5 |
0.7 |
| Fatal bleeding |
0.8 |
0.6 |
*Patients were scheduled to undergo angiography 48 to 192 hours after the start of study medication. For patients who did not undergo angiography, the primary end point was death or recurrent MI by day 8 or by hospital discharge if prior to day 8
†Major bleeding was defined as intracranial bleeding or bleeding associated with a fall in hemoglobin > 5 g/dL.
Learn more about the CLARITY Trial
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: Drug Interactions.*). 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.*). Consider alternative treatment or treatment strategies in patients identified as CYP2C19 poor metabolizers (See Dosage and Administration.*).
Important Safety Information
PLAVIX is contraindicated in patients with active pathological bleeding such as peptic ulcer or intracranial hemorrhage.
PLAVIX is contraindicated in patients with hypersensitivity (eg, anaphylaxis) to clopidogrel or any component of the product. (See Adverse Reactions.*)
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. (See Drug Interactions.*)
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.
Co-administering warfarin with PLAVIX increases the risk of bleeding.
Co-administration of PLAVIX and NSAIDs increases the risk of gastrointestinal bleeding.
Nursing mothers: Discontinue drug or nursing, taking into consideration importance of drug to mother.
*Please See the Full PLAVIX Prescribing Information, Including BOXED WARNING
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 end point of cardiovascular death, myocardial infarction (MI), or stroke as well as the rate of a combined end point 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 end point of death, reinfarction, 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 end point of new ischemic stroke (fatal or not), new MI (fatal or not), and other vascular death.