Pladox Clopidogrel Bisulfate Tablets

PLADOX™
Clopidogrel Tablets USP 75 mg

 

Each film-coated tablet contains:

Clopidogrel Bisulfate U.S.P.

Equivalent to Clopidogrel 75 mg

Excipients q.s.

Approved colours are used.

 

PLADOX (Clopidogrel Bisulfate) is a thienopyridine class inhibitor of P2Y12 ADP platelet receptors. Chemically it is methyl (+)-(S)-ᾳ-(2-chlorophenyl)-6,7-dihydrothieno[3,2-c]pyridhie- 5(4H)-acetate sulfate(1:1) Clopidogrel is an inhibitor of platelet aggregation. A variety of drugs that inhibit platelet function have been shown to decrease morbid events in people with established cardiovascular atherosclerotic disease as evidenced by stroke or transient ischemic attacks, myocardial infarction, unstable angina or the need for vascular bypass or angioplasty. This indicates that platelets participate in the initiation and/or evolution of these events and that inhibiting them can reduce the event rate. Clopidogrel selectively inhibits the binding of adenosine diphosphate (ADP) to its platelet receptor and the subsequent ADP-mediated activation of the glycoprotein GPIIb/IIIa complex, thereby inhibiting platelet aggregation.

 

INDICATIONS AND USAGE

PLADOX is indicated for the reduction of atherothrombotic events as follows:

Recent MI, Recent Stroke or Established Peripheral Arterial Disease

For patients with a history of recent myocardial infarction (Ml), recent stroke, or established peripheral arterial disease, dopidogrel bisulfate has been shown to reduce the rate of a combined endpoint of new ischemic stroke (fatal or not), new MI (fatal or not), and other vascular death.

Acute Coronary Syndrome

For patients with acute coronary syndrome (unstable angina/non-Q-wave MI) including patients who are to be managed medically and those who are to be managed with percutaneous coronary intervention (with or without stent or CABG, clopidogel bisulfate has been shown to decrease the rate of a combined endpoint of cardiovasular death as well as the rate of a combined endpoint of cardiovascular death, MI, stroke, or refractory ischemia.

 

CONTRAINDICATIONS

The use of clopidogrel bisulfate is contraindicated in the following conditions:

Hypersensitivity to the drug substance or any component of the product. Active pathological bleeding such as peptic ulcer or intracranial hemorrhage.

 

WARNINGS

Thrombotic thrombocytopenic purpura (TTP).

TTP has been reported rarely following use of clopidogrel bisulfate, sometimes after a short exposure (<2 weeks). TTP is a serious condition that can be fatal and requires urgent treatment including plasmapheresis (plasma exchange). It is characterized by thrombocytopenia, microangiopathic hemolytic anemia (schistocytes [fragmented RBCs] seen on peripheral smear), neurological findings, renal dysfunction, and fever.

 

PRECAUTIONS

General

PLADOX (Clopidogrel bisulfate) prolongs the bleeding time and therefore should be used with caution in patients who may be at risk of increased bleeding from trauma, surgery, or other pathological conditions (particularly gastrointestinal and intraocular). If a patient is to undergo elective surgery and an antiplatelet effect is not desired, clopidogrel bisulfate should be discontinued 5 days prior to surgery. Due to the risk of bleeding and undesirable hematological effects, blood cell count determination and/or other appropriate testing should be promptly considered, whenever such suspected clinical symptoms arise during the course of treatment.

Use in Hepatically Impaired Patients

Experience is limited in patients with severe hepatic disease, who may have bleeding diatheses. Clopidogrel bisulfate should be used with caution in this population.

Use in Renally Impaired Patients

Experience is limited in patients with severe renal impairment. Pladox should be used with caution in this population.

 

Drug Interactions

Aspirin

Aspirin did not modify the clopidogrel-mediated inhibition of ADP-induced platelet aggregation. Concomitant administration of 500 mg of aspirin twice a day for 1 day did not significantly increase the prolongation of bleeding time induced by clopidogrel bisulfate. PLADOX (Clopidogrel bisulfate) potentiated the effect of aspirin on collagen-induced platelet aggregation. PLADOX (Clopidogrel bisulfate) and aspirin have been administered together for up to one year.

Heparin

In a study in healthy volunteers, PLADOX did not necessitate modification of the heparin dose or alter the effect of heparin on coagulation. Co-administration of heparin had no effect on inhibition of platelet aggregation induced by clopidogrel bisulfate.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

In healthy volunteers receiving naproxen, concomitant administration of PLADOX was associated with increased occult gastrointestinal blood loss. NSAIDs and Pladox should be co-administered with caution.

 

ADVERSE REACTIONS

The overall tolerability of Clopidogrel Bisulfate in CAPRIE was similar to that of aspirin regardless of age, gender and race, with an approximately equal incidence (13%) of patient withdrawing from treatment because of adverse reactions.

Hemorrhagic

In CAPRIE patients receiving clopidogrel bisulfate, gastrointestinal hemorrhage occurred at a rate of 2%, and required hospitalization in 0.7%. In patients receiving aspirin, the corresponding rates were 2.7% and 1.1%, respectively. The incidence of intracranial hemorrhage was 0.4% for clopidogrel bisulfate compared to 0.5% for aspirin. In CURE, PLADOX (Clopidogrel bisulfate) use with aspirin was associated with an increase in bleeding compared to placebo with aspirin. There was an excess in major bleeding in patients receiving clopidogrel bisulfate plus aspirin compared with placebo plus aspirin, primarily gastrointestinal and at puncture sites.

 

OVERDOSAGE

Overdose following PLADOX (Clopidogrel bisulfate) administration may lead to prolonged bleeding time and subsequent bleeding complications. A single oral dose of clopidogrel at 1500 or 2000 mg/kg was lethal to mice and to rats and at 3000 mg/kg to baboons. Symptoms of acute toxicity were vomiting (in baboons), prostration, difficulty breathing, and gastrointestinal hemorrhage in all species.

Nursing Mothers

Studies in rats have shown that PLADOX (Clopidogrel bisulfate) and/or its metabolites are excreted in the milk. It is not known whether this drug is excreted in human milk.

Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the nursing woman.

Pediatric Use

Safety and effectiveness in the pediatric population have not been established.

 

DOSAGE AND ADMINISTRATION

Recent MI, Recent Stroke or Established Peripheral Arterial Disease

The recommended daily dose of PLADOX (Clopidogrel bisulfate) tablets is 75 mg once daily.

Acute Coronary Syndrome

For patients with acute coronary syndrome (unstable angina/non-Q-wave MI), PLADOX should be initiated with a single 300 mg loading dose and then continued at 75 mg once daily. Aspirin (75 mg to 325 mg once daily) should be initiated and continued in combination with PLADOX (clopidogrel bisulfate). In CURE, most patients with Acute Coronary Syndrome also received heparin acutely. Clopidogrel tablets can be administered with or without food.

No dosage adjustment is necessary for elderly patients or patients with renal disease.

 

STORAGE

Store below 30°C. Protect from direct sun light.

Keep out of reach of children.

 

Presentation

3 strips of 10 tablets each.

 

NAFDAC Reg. No.: A4-5967

 

Marketed by

Fidson Healthcare Plc.

268, Ikorodu Road,

Obanikoro, Lagos, Nigeria.

info@fidson.com

www.fidson.com

 

Manufactured by

V. S. International Pvt. Ltd.

Plot No.: 17&18, Golden Indl. Estate,

Somnath Road, Dabhei, Daman- 396215, India.