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.

Table 6: Outcome Events in the CAPRIE Primary Analysis
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

Figure 7: Fatal or Non-Fatal Vascular Events in the CAPRIE Study
(click image for full-size original)

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

Figure 8: Hazard Ratio and 95% CI by Baseline Subgroups in the CAPRIE Study
(click image for full-size original)

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
Remedy_Label
(click image for full-size original)
MM3
(click image for full-size original)
CLOPIDOGREL clopidogrel bisulfate tablet, film coated
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:70518-1898(NDC:65862-357)
Route of Administration ORAL DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
CLOPIDOGREL BISULFATE (CLOPIDOGREL) CLOPIDOGREL 75 mg
Inactive Ingredients
Ingredient Name Strength
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
Product Characteristics
Color pink Score no score
Shape ROUND (Biconvex) Size 9mm
Flavor Imprint Code E;34
Contains
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:70518-1898-0 30 TABLET, FILM COATED in 1 BLISTER PACK None
2 NDC:70518-1898-1 30 TABLET, FILM COATED in 1 BLISTER PACK None
3 NDC:70518-1898-2 90 TABLET, FILM COATED in 1 BOTTLE, PLASTIC None
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA090540 02/22/2019
Labeler — REMEDYREPACK INC. (829572556)

Revised: 02/2024 REMEDYREPACK INC.

All MedLibrary.org resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.

This site is provided for educational and informational purposes only, in accordance with our Terms of Use, and is not intended as a substitute for the advice of a medical doctor, nurse, nurse practitioner or other qualified health professional.

Privacy Policy | Copyright © 2024. All Rights Reserved.