Plagerine Clopidogrel Bisulfate Tablets

Plagerine

CLOPIDOGREL TABLETS USP 75 mg

 

COMPOSITION

Each film-coated tablet contains : Clopidogrel Bisulfate USP equivalent to Clopidogrel 75 mg

 

CHEMISTRY

methyl (+)-(S)-(2- chlorophenyl)-6,7-dihydrothieno[3,2-c] pyridine-5(4H)-acetatesulfate (1:1).

 

PHARMACOLOGICAL CATEGORY

Antiplatelet Agent.

 

PHARMACOLOGY

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 atherosclerotic cardiovascular disease as evidenced by stroke or transient ischemic attacks, myocardial infarction, or need for 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.

 

Pharmacodynamics

Clopidogrel selectively inhibits the binding of adenosine diphosphate (ADP) to its platelet receptor and the subsequent A.P. mediated activation of the glycoprotein GPllb/IIIa complex, thereby inhibiting platelet aggregation. Biotransformation of clopidogrel is necessary to produce inhibition of platelet aggregation, but an active metabolite responsible for the activity of the drug has not been isolated. Clopidogrel also inhibits platelet aggregation induced by agonists other than ADP by blocking the amplification of platelet activation by released A.P. Clopidogrel does not inhibit phosphodiesterase activity.

 

Pharmacokinetics

Clopidogrel is extensively metabolized by the liver. The main circulating metabolite is the carboxylic acid derivative, and it too has no effect on platelet aggregation. It represents about 85% of the circulating drug related compounds in plasma.

The elimination half-life of the main circulating metabolite was 8 hours after single and repeated administration. Covalent binding to platelets accounted for 2% of radiolabel with a half-life of 11 days. Clopidogrel is rapidly absorbed after oral administration of repeated doses of 75 mg clopidogrel (base), with peak plasma levels (-/=3 mg/ L) of the main circulating metabolite occurring approximately 1 hour after dosing. The pharmacokinetics of the main circulating metabolite are linear (plasma concentrations increased in proportion to dose) in the dose range of 50 to 150 mg of clopidogrel.

Absorption is at least 50% based on urinary excretion of clopidogrel-related metabolites.

Clopidogrel undergoes rapid hydrolysis into its carboxylic acid derivative.

 

INDICATIONS AND USES

Clopidogrel bisulfate is indicated for the reduction of atherosclerotic events (myocardial infarction, stroke, and vascular death) in patients with atherosclerosis documented by recent stroke, recent myocardial infarction, or established peripheral arterial disease.

 

CONTRAINDICATIONS

The use of CLOPIDOGREL is contraindicated to Hypersensitivity and active pathological bleeding such as peptic ulcer or intracranial hemorrhage.

 

SIDE EFFECTS/ADVERSE REACTIONS

Body as a Whole General Disorders

Chest Pain, Accidental Injury, Influenza- like symptoms, Pain, Fatigue.

 

Cardiovascular disorders, general

Edema, Hypertension.

 

Central & peripheral peripheral nervous system disorders

Headache, Dizziness.

 

Gastrointestinal system disorders

Abdominal pain, Dyspepsia, Diarrhea, Nausea.

 

Metabolic & nutritional disorders

Hypercholesterolemia

 

Musculo-skeletal system disorders

Arthralgia, Back Pain.

 

Platelet, bleeding & clotting disorders

Purpura, Epistaxis

 

Psychiatric disorders

Depression

 

Respiratory system disorders

Upper respiratory tract infection, Dyspnea, Rhinitis, Bronchitis, Coughing.

 

Skin & appendage disorders

Rash, Pruritus.

 

Urinary system disorders

Urinary tract infection.

 

PRECAUTIONS/WARNINGS

As with other anti-platelet agents, CLOPIDOGREL should be used with caution in patients who may be at risk of increased bleeding from trauma, surgery, or other pathological conditions.

If a patient is to undergo elective surgery and an antiplatelet effect is not desired,
CLOPIDOGREL should be discontinued 7 days prior to surgery.

 

DRUG INTERACTIONS

Aspirin did not modify the clopidogrel- mediated inhibition of A.P. induced platelet aggregation. Co-administration of heparin had no effect on inhibition of platelet aggregation induced by Clopidogrel.

Clopidogrel should be co-administered with caution in Nonsteroidal Anti-Inflammatory Drugs.

 

USE IN PREGNANCY AND LACTATION

No adequate and well-controlled studies in pregnant women. Clopidogrel should be used during pregnancy only if clearly needed.

 

Nursing Mothers

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.

 

DOSAGE AND ADMINISTRATION

Hypertension

The recommended dose of CLOPIDOGREL is 75 mg once daily with or without food. No dosage adjustment is necessary for elderly patients or patients with renal disease.

 

OVERDOSAGE, SYMPTOMS AND ANTIDOTE

One case of deliberate overdosage with CLOPIDOGREL was reported in the large, controlled clinical study. A 34- year- old woman took a single 1,050- mg dose of CLOPIDOGREL (equivalent to 14 standard 75- mg tablets). There were no associated adverse events. No special therapy was instituted, and she recovered without sequelae. Based on biological plausibility, platelet transfusion may be appropriate to reverse the pharmacological effects of CLOPIDOGREL if quick reversal is required.

 

STORAGE

Store below 30oC.

 

DATE OF PUBLICATION: MAR. 2002

 

NAFDAC Reg. No.: A4-5107

 

Manufactured by

MICRO LABS LIMITED

92, SIPCOT, HOSUR-635 126, INDIA.