Safety and Side Effects


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: 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–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.


Tolerability1

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)
Purpura/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)

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).1


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.

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 bleeding.


Major bleeding rates were DOSE DEPENDENT on aspirin1

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


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 81*		 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.

  • Major bleeding rates were consistent across subgroups and type of fibrinolytic or heparin therapy1,7

Learn more about the CLARITY Trial

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.