Plavix (Clopidogrel)
 Only available by prescription.
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Plavix (Clopidogrel)
Description:
Indications and Clinical Use
MI, Stroke or Established Peripheral Arterial Disease
PLAVIX (clopidogrel bisulfate) is indicated for the secondary prevention of atherothrombotic events (myocardial infarction, stroke and vascular death) in patients with atherosclerosis documented by stroke, myocardial infarction, or established peripheral arterial disease.
Acute Coronary Syndrome
PLAVIX, in combination with acetylsalicylic acid (ASA), is indicated for the early and long-term secondary prevention of atherothrombotic events (myocardial infarction, ischemic stroke, cardiovascular death and/or refractory ischemia) in patients with acute coronary syndromes- without ST segment elevation (ie. unstable angina or non-Q-wave myocardial infarction). These benefits of PLAVIX have been shown only when these patients were concomitantly treated with ASA in addition to other standard therapies. These benefits were also seen in patients who were managed medically and those who were managed with percutaneous coronary intervention (with or without stent) or CABG (coronary artery bypass graft).
For patients with ST-segment elevation acute myocardial infarction, PLAVIX has been shown to reduce the rate of an endpoint of all-cause mortality and the rate of a combined endpoint of death, re-infarction or stroke.
Warnings and Precautions
General
As with other antiplatelet agents, when considering prescribing PLAVIX (clopidogrel bisulfate), physicians should inquire whether the patient has a history of bleeding. Clopidogrel should be used with caution in patients who may be at risk of increased bleeding from recent trauma, surgery or other pathological condition(s).
Because of the increased risk of bleeding, the concomitant administration of warfarin with clopidogrel should be undertaken with caution (see Drug Interactions).
In patients with recent transient ischaemic attack (TIA) or stroke who are at high risk of 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 (see Drug Interactions).
If a patient is to undergo elective surgery, consideration should be given to discontinue PLAVIX 5 to 7 days prior to surgery to allow for the reversal of the effect.
Platelet transfusion may be used to reverse the pharmacological effects of PLAVIX when quick reversal is required.
Gastrointestinal
Active GI Lesions
PLAVIX (clopidogrel bisulfate) prolongs bleeding time. Although PLAVIX has shown a lower incidence of gastrointestinal bleeding compared to ASA in a large controlled clinical trial (CAPRIE), PLAVIX should not be used in patients who have lesions with a propensity to bleed. In CURE, the incidence of major GI bleeding was 1.3% versus 0.7% (PLAVIX+ASA versus placebo+ASA, respectively).
In patients taking PLAVIX, drugs that might induce GI lesions should be used with caution.
Hematologic
Thrombotic Thrombocytopenic Purpura (TTP)
Thrombotic thrombocytopenic purpura (TTP) has been reported rarely following the use of PLAVIX, but it can occur anytime during the first year of exposure. Few cases have been reported after more than one year of exposure. TTP is a potentially fatal condition requiring prompt treatment with plasmapheresis. It is characterized by thrombocytopenia, microangiopathic hemolytic anemia (schistocytes [fragmented RBC's] seen on peripheral smear), neurological findings, renal dysfunction, and fever.
Hepatic/Biliary/Pancreatic
Experience is limited in patients with moderate hepatic impairment who may have bleeding diatheses. As with any patient exhibiting hepatic impairment, liver function should be carefully monitored and PLAVIX should be used with caution.
In the CAPRIE study, there were 344 hepatically impaired patients (Alkaline phosphatase >300 U/L, or ALT >120 U/L, or AST >75 U/L) and 168 received clopidogrel for a mean duration of 18 months. The adverse events were more common in this population, compared to the rest of the CAPRIE population, and more common in the clopidogrel (N=168) than in the ASA (N=176) group (any bleeding disorders, N=17 vs N=14; any rash, N=11 vs N=6; diarrhea, N=8 vs N=3, respectively).
Peri-Operative Considerations
If a patient is to undergo elective surgery, consideration should be given to discontinue PLAVIX 5 to 7 days prior to surgery to allow for a reversal of its effect.
Clopidogrel should be used with caution in patients who may be at risk of increased bleeding from recent surgery.
Renal
Therapeutic experience with clopidogrel is limited in patients with severe and moderate renal impairment. Therefore, PLAVIX should be used with caution in these patients.
Special Populations
Pregnant Women
There are no adequate and well-controlled studies in pregnant women.
Reproduction studies have been performed in rats at doses up to 500 mg/kg per day and in rabbits at doses up to 300 mg/kg per day and have revealed no evidence of impaired fertility or harm to the fetus due to clopidogrel. Because animal reproduction studies are not always predictive of a human response, PLAVIX should be used during pregnancy only if the potential benefits outweigh the potential risks to the fetus.
Nursing Women
Studies in rats have shown that clopidogrel and/or its metabolites are excreted in milk. It is not known whether this drug is excreted in human milk. Therefore, clopidogrel should not be used by lactating women.
Pediatrics (<18 years of age)
Safety and effectiveness in subjects below the age of 18 have not been established.
Plavix (Clopidogrel) Manufacturer:
Sanofi-Synthelabo
Plavix (Clopidogrel) Side Effects:
Adverse Drug Reaction Overview
The safety profile of clopidogrel has been evaluated in clinical trials in more than 42 000 patients and further assessed during post-marketing experience.
Of the patients who participated in the CAPRIE, CURE and CLARITY double-blind international clinical trials, approximately 50% were elderly patients (>65 years) and 15% were 75 years and older. 9000 patients were treated for one year or more. In COMMIT, approximately 58% of the patients treated with PLAVIX were 60 years and older, 26% of whom were 70 years and older.
The most frequent adverse drug reactions (≥1%) with PLAVIX (with or without associated ASA) in controlled clinical trials were hemorrhage and bleeding disorders including purpura, any rash, dyspepsia, abdominal pain and diarrhea (see Clinical Trial Adverse Drug Reactions).
The most serious adverse drug reactions from controlled clinical trials rarely reported (<1%) were bleeding and clotting disorders including gastrointestinal hemorrhage, hemorrhagic ulcer and hemothorax.
Blood Disorders
agranulocytosis/granulocytopenia, aplastic anemia, neutropenia and thrombocytopenia.
Gastrointestinal System Disorders
duodenal, gastric or peptic ulcer, gastritis.
Skin Disorders
any rash and bullous eruption.
The overall incidence of study drug discontinuation because of adverse events was similar in both groups in CAPRIE (PLAVIX 11.9% and ASA 11.9%). In CURE, study drug discontinuation occurred in 5.8 % of patients with PLAVIX plus ASA and 3.9% of patients with placebo plus ASA. In CLARITY, study drug discontinuation was greater in the placebo group (8.6%) compared with the clopidogrel group (6.9%). In COMMIT, the overall incidence of discontinuations was similar between the two treatment groups (2.4% in the clopidogrel group versus 2.2% in the placebo group).
Clinical Trial Adverse Drug Reactions
Because clinical trials are conducted under very specific conditions the adverse reaction rates observed in the clinical trials may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug. Adverse drug reaction information from clinical trials is useful for identifying drug-related adverse events and for approximating rates.
CAPRIE
With few exceptions (see Table 1) the overall tolerability of PLAVIX was similar regardless of age, sex and race. However, in women there was a slightly higher incidence of bleeding disorders in the clopidogrel group (11.36% vs 9.88%).
Clinically Important Adverse Events
The clinically important adverse events observed in CAPRIE were the following:
Bleeding and Clotting Disorders
One case of Henoch-Schönlein purpura (acute visceral symptoms: vomiting, diarrhea, abdominal distension, hematuria, renal colic) was reported in a patient taking PLAVIX. The patient recovered without sequellae within one month. Rare cases of platelet count ≤30 000/mm3 have been reported. The overall incidence of bleeding on clopidogrel and ASA was the same (9.3%). The incidence of severe cases was 1.4% and 1.6% in the clopidogrel and ASA groups respectively. The overall incidence of other bleeding disorders was higher in the clopidogrel group (7.3%) compared to ASA (6.5%). However, the incidence of severe events was similar in both treatment groups (0.6% vs 0.4%).
Gastrointestinal
Overall, the incidence of gastrointestinal events (e.g. abdominal pain, dyspepsia, gastritis and constipation) in patients receiving PLAVIX (clopidogrel bisulfate) was 27.1%, compared to 29.8% in those receiving ASA. The incidence of patients withdrawing from treatment because of gastrointestinal adverse reactions was 3.2% for PLAVIX and 4.0% for ASA.
Hepatic and Biliary Disorders
The overall incidence of hepatic and biliary disorders was similar in patients treated with clopidogrel (3.5%) compared to ASA (3.4%). The most frequent events were increased liver enzymes and bilirubinemia.
Skin Disorders
The incidence of skin and appendage disorders in patients receiving PLAVIX was 15.8% (0.7% serious); the corresponding rate in ASA patients was 13.1% (0.5% serious). There was no notable difference between treatment groups in the incidence of bullous eruptions (0.23% PLAVIX versus 0.16% ASA). One case of a severe bullous eruption was reported in a patient taking PLAVIX. The overall incidence of patients withdrawing from treatment because of skin and appendage disorders adverse reactions was 1.5% for PLAVIX and 0.8% for ASA.
A summary of the clinically relevant adverse effects observed in CAPRIE are presented in Table 1. In CAPRIE, patients with a known intolerance to ASA were excluded from the study.
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| Product Code:1723 |
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