Clopidogrel Bisulfate

1 ) – Initiate clopidogrel tablets with a single 300 mg oral loading dose and then continue at 75 mg once daily. – Initiating clopidogrel tablets without a loading dose will delay establishment of an antiplatelet effect by several days.

● Recent MI, recent stroke, or established peripheral arterial disease: 75 mg once daily orally without a loading dose. 1 Acute Coronary Syndrome In patients who need an antiplatelet effect within hours, initiate clopidogrel tablets with a single 300 mg oral loading dose and then continue at 75 mg once daily.

1 )] . 2 )] .

6 ADVERSE REACTIONS Bleeding, including life-threatening and fatal bleeding, is the most commonly reported adverse reaction. 1 ) To report SUSPECTED ADVERSE REACTIONS, contact Torrent Pharma Inc. gov/medwatch. 1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions and durations of follow-up, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Clopidogrel tablets has been evaluated for safety in more than 54,000 patients, including over 21,000 patients treated for one year or more. The clinically important adverse reactions observed in trials comparing clopidogrel tablets plus aspirin to placebo plus aspirin and trials comparing clopidogrel tablets alone to aspirin alone are discussed below.

Bleeding CURE In CURE, clopidogrel tablets use with aspirin was associated with an increase in major bleeding (primarily gastrointestinal and at puncture sites) compared to placebo with aspirin (see Table 1). 2%) were the same in both groups.

Other bleeding events that were reported more frequently in the clopidogrel group were epistaxis, hematuria, and bruise. The overall incidence of bleeding is described in Table 1.

Table 1:

CURE Incidence of Bleeding Complications (% patients) * Life-threatening and other major bleeding. † Led to interruption of study medication. 4 COMMIT In COMMIT, similar rates of major bleeding were observed in the clopidogrel tablets and placebo groups, both of which also received aspirin (see Table 2).

Table 2:

Incidence of Bleeding Events in COMMIT (% patients) * Major bleeds were cerebral bleeds or noncerebral bleeds thought to have caused death or that required transfusion. 1%, respectively. 5% for aspirin. Other bleeding events that were reported more frequently in the clopidogrel tablets group were epistaxis and hematoma.

5 WARNINGS AND PRECAUTIONS CYP2C19 inhibitors: Avoid concomitant use of omeprazole or esomeprazole. 1 ) Bleeding: Clopidogrel tablets increases risk of bleeding. 2 ) Discontinuation: Premature discontinuation increases risk of cardiovascular events.

Discontinue 5 days prior to elective surgery that has a major risk of bleeding. 3 ) Thrombotic thrombocytopenic purpura (TTP) has been reported. 4 ) Cross-reactivity among thienopyridines has been reported. 1 Diminished Antiplatelet Activity in Patients with Impaired CYP2C19 Function Clopidogrel is a prodrug.

Inhibition of platelet aggregation by clopidogrel is achieved through an active metabolite. The metabolism of clopidogrel to its active metabolite can be impaired by genetic variations in CYP2C19 [see Boxed Warning ]. The metabolism of clopidogrel can also be impaired by drugs that inhibit CYP2C19, such as omeprazole or esomeprazole.

1 )] . 2 General Risk of Bleeding P2Y12 inhibitors (thienopyridines), including clopidogrel tablets, increase the risk of bleeding. P2Y12 inhibitors (thienopyridines), inhibit platelet aggregation for the lifetime of the platelet (7 to 10 days).

Because the half-life of clopidogrel's active metabolite is short, it may be possible to restore hemostasis by administering exogenous platelets; however, platelet transfusions within 4 hours of the loading dose or 2 hours of the maintenance dose may be less effective.

Use of drugs that induce the activity of CYP2C19 would be expected to result in increased drug levels of the active metabolite of clopidogrel and might potentiate the bleeding risk. 3 )]. 7 )]. 3 Discontinuation of Clopidogrel Tablets Discontinuation of clopidogrel tablets increases the risk of cardiovascular events.

, to treat bleeding or for surgery with a major risk of bleeding), restart it as soon as possible. When possible, interrupt therapy with clopidogrel tablets for five days prior to such surgery. Resume clopidogrel tablets as soon as hemostasis is achieved.

1 Active Bleeding Clopidogrel tablets are contraindicated in patients with active pathological bleeding such as peptic ulcer or intracranial hemorrhage. 2 )] .