Clopidogrel (Page 5 of 5)
14.2 Recent Myocardial Infarction, Recent Stroke, or Established Peripheral Arterial Disease
CAPRIE
The CAPRIE trial was a 19,185-patient, 304-center, international, randomized, double-blind, parallel-group study comparing clopidogrel (75 mg daily) to aspirin (325 mg daily). To be eligible to enroll, patients had to have: 1) recent history of myocardial infarction (within 35 days); 2) recent histories of ischemic stroke (within 6 months) with at least a week of residual neurological signs; and/or 3) established peripheral arterial disease (PAD). Patients received randomized treatment for an average of 1.6 years (maximum of 3 years).
The trial’s primary outcome was the time to first occurrence of new ischemic stroke (fatal or not), new myocardial infarction (fatal or not), or other vascular death. Deaths not easily attributable to nonvascular causes were all classified as vascular.
Patients | Clopidogrel n=9599 | Aspirin n=9586 |
Ischemic stroke (fatal or not) | 438 (4.6%) | 461 (4.8%) |
MI (fatal or not) | 275 (2.9%) | 333 (3.5%) |
Other vascular death | 226 (2.4%) | 226 (2.4%) |
Total | 939 (9.8%) | 1020 (10.6%) |
As shown in Table 6, clopidogrel was associated with a lower incidence of outcome events, primarily MI. The overall relative risk reduction (9.8% vs 10.6%) was 8.7%, p=0.045. Similar results were obtained when all-cause mortality and all-cause strokes were counted instead of vascular mortality and ischemic strokes (risk reduction 6.9%). In patients who survived an on-study stroke or myocardial infarction, the incidence of subsequent events was lower in the clopidogrel group. The curves showing the overall event rate are shown in Figure 7. The event curves separated early and continued to diverge over the 3-year follow-up period.
Figure 7: Fatal or Nonfatal Vascular Events in the CAPRIE Study
The statistical significance favoring clopidogrel over aspirin was marginal (p=0.045). However, because aspirin is itself effective in reducing cardiovascular events in patients with recent myocardial infarction or stroke, the effect of clopidogrel is substantial. The CAPRIE trial enrolled a population that had recent MI, recent stroke, or PAD. The efficacy of clopidogrel relative to aspirin was heterogeneous across these subgroups (p=0.043) (see Figure 8). Nonetheless, this difference may be a chance occurrence because the CAPRIE trial was not designed to evaluate the relative benefit of clopidogrel over aspirin in the individual patient subgroups. The benefit was most apparent in patients who were enrolled because of peripheral arterial disease and less apparent in stroke patients. In patients who were enrolled in the trial on the sole basis of a recent myocardial infarction, clopidogrel was not numerically superior to aspirin.
Figure 8: Hazard Ratio and 95% CI by Baseline Subgroups in the CAPRIE Study
14.3 No Demonstrated Benefit of Clopidogrel plus Aspirin in Patients with Multiple Risk Factors or Established Vascular Disease
CHARISMA
The CHARISMA trial was a 15,603 subject, randomized, double-blind, parallel group study comparing clopidogrel (75 mg daily) to placebo for prevention of ischemic events in patients with vascular disease or multiple risk factors for atherosclerosis. All subjects were treated with aspirin 75 to 162 mg daily. The mean duration of treatment was 23 months. The study failed to demonstrate a reduction in the occurrence of the primary endpoint, a composite of CV death, MI, or stroke. A total of 534 (6.9%) patients in the clopidogrel group versus 573 (7.4%) patients in the placebo group experienced a primary outcome event (p=0.22). Bleeding of all severities was more common in the subjects randomized to clopidogrel.
16 HOW SUPPLIED/STORAGE AND HANDLING
Clopidogrel Tablets USP, 75 mg are pink colored, round, biconvex, beveled edge, film-coated tablets debossed with ‘E’ on one side and ‘34’ on the other side.
NDC: 70518-1898-00
NDC: 70518-1898-01
NDC: 70518-1898-02
PACKAGING: 30 in 1 BLISTER PACK
PACKAGING: 30 in 1 BLISTER PACK
PACKAGING: 90 in 1 BOTTLE PLASTIC
Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Protect from moisture.
Preserve in well-closed containers.
Repackaged and Distributed By:
Remedy Repack, Inc.
625 Kolter Dr. Suite #4 Indiana, PA 1-724-465-8762
17 PATIENT COUNSELING INFORMATION
Advise patients to read FDA approved patient labeling (
Medication Guide).
Discontinuation
Advise patients not to discontinue clopidogrel without first discussing it with the healthcare provider who prescribed it
[see
Warnings and Precautions (5.3)]
.
Bleeding
Advise patients that they:
- will bruise and bleed more easily
- will take longer than usual to stop bleeding
- must report any unanticipated, prolonged, or excessive bleeding, or blood in their stool or urine [see Warnings and Precautions (5.2)]
Thrombotic Thrombocytopenic Purpura
Instruct patients to get prompt medical attention if they experience symptoms of TTP that cannot otherwise be explained
[see
Warnings and Precautions (5.4)]
.
Invasive Procedures
Advise patients to inform physicians and dentists that they are taking clopidogrel before any surgery or dental procedure
[see
Warnings and Precautions (5.2,
5.3)]
.
Proton Pump Inhibitors
Advise patients not to take omeprazole or esomeprazole while taking clopidogrel. Dexlansoprazole, lansoprazole, and pantoprazole had less pronounced effects on the antiplatelet activity of clopidogrel than did omeprazole or esomeprazole
[see
Drug Interactions (7.2)]
.
Repackaged By / Distributed By: RemedyRepack Inc.
625 Kolter Drive, Indiana, PA 15701
(724) 465-8762
Medication Guide
PRINCIPAL DISPLAY PANEL
DRUG: Clopidogrel
GENERIC: Clopidogrel Bisulfate
DOSAGE: TABLET, FILM COATED
ADMINSTRATION: ORAL
NDC: 70518-1898-0
NDC: 70518-1898-1
NDC: 70518-1898-2
COLOR: pink
SHAPE: ROUND
SCORE: No score
SIZE: 9 mm
IMPRINT: E;34
PACKAGING: 30 in 1 BLISTER PACK
PACKAGING: 30 in 1 BLISTER PACK
PACKAGING: 90 in 1 BOTTLE PLASTIC
ACTIVE INGREDIENT(S):
- CLOPIDOGREL BISULFATE 75mg in 1
INACTIVE INGREDIENT(S):
- CROSPOVIDONE (120 .MU.M)
- HYDROGENATED CASTOR OIL
- LOW-SUBSTITUTED HYDROXYPROPYL CELLULOSE, UNSPECIFIED
- HYPROMELLOSE 2910 (15 MPA.S)
- FERRIC OXIDE RED
- LACTOSE MONOHYDRATE
- MANNITOL
- MICROCRYSTALLINE CELLULOSE
- POLYETHYLENE GLYCOL 6000
- TITANIUM DIOXIDE
- TRIACETIN
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Labeler — REMEDYREPACK INC. (829572556) |
Revised: 02/2024 REMEDYREPACK INC.
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