Norplat

Main information

  • Trade name:
  • Norplat 75mg Tablet, film coated
  • Dosage:
  • 75mg
  • Pharmaceutical form:
  • Tablet, film coated
  • Units in package:
  • Alu/ Alu Blister pack x 7's (box of 28's)
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug
  • Manufactured by:
  • Getz Pharma Pvt Ltd

Documents

Localization

  • Available in:
  • Norplat 75mg Tablet, film coated
    Philippines
  • Language:
  • English

Status

  • Source:
  • FDA - Food And Drug Administration - Philippines
  • Authorization number:
  • DR-XY32200
  • Authorization date:
  • 09-07-2019
  • Last update:
  • 26-01-2017

Summary of Product characteristics: dosage, interactions, side effects

CONTRAINDICATIONS

Clopidogrel is contraindicated in:

Patients who have shown hypersensitivity to the drug

or any component of the medication.

Patients who suffer from active pathological bleeding

such as peptic ulcer or intracranial hemorrhage.

PRECAUTIONS

General

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, consideration

should be given to stopping clopidogrel 5 days before

surgery.

Clopidogrel should be used with caution in patients

who have lesions with a propensity to bleed (such as

ulcers). Drugs that might induce such le

sions should

be used in caution in patients taking clopidogrel.

Hematological

Clopidogrel should not be administered to patients with

hematopoietic

disorders

such

neutropenia

thrombocytopenia, hemorrhagic diathesis or other hemorrhagic

disorders associated with a prolonged bleeding time. Full blood

count should be performed before starting treatment and every

two weeks during the first three months of therapy. If clopidogrel

is discontinued during this period, a full blood count should be

performed within two weeks of stopping treatment.

Hepatic Impaired Patients

Experience is limited in patients with severe hepatic disease,

who may have bleeding diatheses. Clopidogrel should be used

with caution in such patients.

Renal Impaired Patients

Experience is limited in patients with severe renal impairment.

Clopidogrel

should be used with caution in such patients.

Pediatric Use

Safety and effectiveness in the population have not been

established.

Pregnancy

Clopidogrel has not been studied in pregnant women. It should

be used during

pregnancy only

clearly needed.

Nursing Mothers

It is not known if clopidogrel is excreted in human milk. Because

many drugs are excreted in human milk, caution should be

exercised when clopidogrel is given to a nursing mother.

Drug Interactions

Aspirin: A pharmacodynamic interaction between clopidogrel

and aspirin is possible, leading to increased risk of bleeding.

Therefore, concomitant use should be undertaken with caution.

However, clopidogrel and aspirin have been administered

together for up to one year.

Heparin: A pharmacodynamic interaction between clopidogrel

and heparin is possible, leading to increased risk of bleedi

Therefore, concomitant use should be undertaken with caution.

Warfarin: Because of the increased risk of bleeding, the

concomitant administration of warfarin with clopidogrel should

be undertaken with caution.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): In healthy

volunteers receiving naproxen, concomitant administration of

clopidogrel was associated with increased occult gastrointestinal

blood loss. NSAIDs and clopidogrel should be co-administered

with caution.

Drugs metabolized by cytochrome P450: At high concentrations

in-vitro, clopidogrel inhibits P450 (2C9). Accordingly, it may

interfere with the metabolism of phenytoin, tamoxifen,

tolbutamide, warfarin, torsemide, fluvastatin, and many non-

steroidal antiinflammatory agents, but there are no data with

which to predict the magnitude of these interactions. Caution

should be used when any of these drugs is co-administe

with clopidogrel.

STORAGE CONDITIONS

Store at temperatures not exceeding 30

Protect from light & moisture.

The expiration date refers to the product correctly stored at

the required conditions.

AVAILABILITY

Clopidogrel (NORPLAT ) 75mg film-coated tablets are available

in Alu-Alu blister packs of 7’s, box of 28 film-coated tablets.

CAUTION

Foods, Drugs, Devices and Cosmetics Act prohibits

dispensing without prescription.

Keep out of reach of children.

DESCRIPTION

Clopidogrel (NORPLAT

) is an inhibitor of ADP-induced platelet

aggregation. It reduces the chance of having a heart attack

or a stroke in people who have already had a heart attack or

a stroke.

Chemically it is methyl (+)-(S)-

-(2-chlorophenyl)-6,7-

dihydrothieno[3,2-c]pyridine-5(4H)-acetate sulfate (1:1). The

molecular

formula

clopidogrel

bisulfate

ClNO

and the structural formula is:

FORMULATION

Clopidogrel (NORPLAT

) is available for oral administration

Clopidogrel (NORPLAT

) Tablets 75mg

Each film-coated tablet contains:

Clopidogrel (as bisulfate).75mg

CLINICAL PHARMACOLOGY

Mechanism of Action

Clopidogrel is an inhibitor of platelet aggregation, that is, a

drug that inhibits the ability of platelets to clump together as

part of a blood clot.

It appears to act by blocking the adenosine phosphate (ADP)

receptors, which prevents fibrinogen binding to the receptor.

This decreases the ability of platelet adhesion and aggregation.

Clopidogrel is a prodrug and requires biotransformation to

produce inhibition of platelet aggregation. The active metabolite

of clopidogrel also inhibits platelet aggregation induced by

agonists other than ADP by blocking the amplification of platelet

activation by released ADP.

Pharmacokinetics

Clopidogrel

after

administration

requires

h ep a tic

biotransformation to an active metabolite. Hepatic activation

is thought to be mediated by the CYP P450 1A subfamily. The

uncharacterized active metabolite is labile and highly

reactive.

Absorption:

Following oral administration, clopidogrel is rapidly absorbed.

Absorption is at least 50% and is not significantly affected by

food. Peak plasma concentrations (roughly 3mg/L) of the

primary circulating metabolite occur at about one hour following

multiple dosing of 75mg/day. Plasma concentrations of the

parent drug are undetectable 2 hours after an oral dose.

Distribution:

Clopidogrel and the main circulating metabolite bind reversibly

to human plasma proteins (98% and 94% respectively).

Metabolism:

Clopidogrel is extensively metabolized in the liver. The main

circulating metabolite is the carboxylic acid derivative, and it

has no effect on platelet aggregation. The active metabolite

appears to be thiol derivative but has not been identified in

plasma.

Elimination:

Clopidogrel and its metabolites are excreted about equally in

urine and feces. The half-life of the carboxylic acid derivative

is about 8 hours.

Special populations:

Renal Ins

ufficiency

After repeated doses of 75mg clopidogrel per day, plasma

levels of the main circulating metabolite were lower in patients

with severe renal impairment (creatinine clearance from 5 to

15mL/min) compared to subjects with moderate renal

impairment (creatinine clearance 30 to 60mL/min) or healthy

subjects. However, the prolongation of bleeding time was

similar. No dose adjustment is required in mild to moderate

renal impaired patients.

THERAPEUTIC INDICATIONS

Clopidogrel (NORPLAT ) is indicated for the reduction

of thrombotic events in patients with recent myocardial

infarction, recent stroke, or established peripheral

arterial disease.

Clopidogrel (NORPLAT ) is used prophylactically in

patients at risk of thromboembolic disorders such as

myocardial infarction, peripheral arterial disease and

stroke.

Clopidogrel (NORPLAT ) is also indicated for acute

coronary syndrome (unstable angina/non-Q-wave MI)

DOSAGE AND ADMINISTRATION

Clopidogrel (NORPLAT

) can be administered with or without

food.

Recent MI, recent stroke, or established peripheral

arterial disease: The recommended daily dose is one

Clopidogrel

(NORPLAT

tablet

(75mg)

d ai l y .

Prophylactic use in patients at risk of thromboembolic

disorders such as MI, peripheral arterial disease and stroke:

T h e

r e c o m m e n d e d

d a i l y

d o s e

o n e

C l o p i d o g r e l (NORPLAT

) tablet (75mg) daily.

Acute coronary syndrome (unstable angina/non-Q

wave MI): Dose should be initiated with a single

300mg loading dose and then continued at 75mg

once daily (with Aspirin 75mg-325mg once daily).

ADVERSE EFFECTS

Clopidogrel is generally well tolerated. However the following

adverse effects have been reported during treatment.

Common: Gastrointestinal disturbances (Diarrhea, abdominal

pain, indigestion and nausea) and dermatological reactions

(rash, pruritis).

Less common: Chest pain, nose bleeds.

Rare: Gastrointestinal bleeding, gastric ulcers, severe

neutropenia or agranulocytosis, thrombocytopenia, thromb

otic

thrombocytopenic purpura, aplastic anemia, membranous

nephropathy with nephrotic syndrome, loss of taste, acute

arthritis.

Clopidogrel bisulfate

C- OCH

75mg Film-Coated Tablet

Antithrombotic

CONTRAINDICATIONS

Clopidogrel is contraindicated in:

Patients who have shown hypersensitivity to the drug

or any component of the medication.

Patients who suffer from active pathological bleeding

such as peptic ulcer or intracranial hemorrhage.

PRECAUTIONS

General

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, consideration

should be given to stopping clopidogrel 5 days before

surgery.

Clopidogrel should be used with caution in patients

who have lesions with a propensity to bleed (such as

ulcers). Drugs that might induce such le

sions should

be used in caution in patients taking clopidogrel.

Hematological

Clopidogrel should not be administered to patients with

hematopoietic

disorders

such

neutropenia

thrombocytopenia, hemorrhagic diathesis or other hemorrhagic

disorders associated with a prolonged bleeding time. Full blood

count should be performed before starting treatment and every

two weeks during the first three months of therapy. If clopidogrel

is discontinued during this period, a full blood count should be

performed within two weeks of stopping treatment.

Hepatic Impaired Patients

Experience is limited in patients with severe hepatic disease,

who may have bleeding diatheses. Clopidogrel should be used

with caution in such patients.

Renal Impaired Patients

Experience is limited in patients with severe renal impairment.

Clopidogrel

should be used with caution in such patients.

Pediatric Use

Safety and effectiveness in the population have not been

established.

Pregnancy

Clopidogrel has not been studied in pregnant women. It should

be used during

pregnancy only

clearly needed.

Nursing Mothers

It is not known if clopidogrel is excreted in human milk. Because

many drugs are excreted in human milk, caution should be

exercised when clopidogrel is given to a nursing mother.

Drug Interactions

Aspirin: A pharmacodynamic interaction between clopidogrel

and aspirin is possible, leading to increased risk of bleeding.

Therefore, concomitant use should be undertaken with caution.

However, clopidogrel and aspirin have been administered

together for up to one year.

Heparin: A pharmacodynamic interaction between clopidogrel

and heparin is possible, leading to increased risk of bleedi

Therefore, concomitant use should be undertaken with caution.

Warfarin: Because of the increased risk of bleeding, the

concomitant administration of warfarin with clopidogrel should

be undertaken with caution.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): In healthy

volunteers receiving naproxen, concomitant administration of

clopidogrel was associated with increased occult gastrointestinal

blood loss. NSAIDs and clopidogrel should be co-administered

with caution.

Drugs metabolized by cytochrome P450: At high concentrations

in-vitro, clopidogrel inhibits P450 (2C9). Accordingly, it may

interfere with the metabolism of phenytoin, tamoxifen,

tolbutamide, warfarin, torsemide, fluvastatin, and many non-

steroidal antiinflammatory agents, but there are no data with

which to predict the magnitude of these interactions. Caution

should be used when any of these drugs is co-administe

with clopidogrel.

STORAGE CONDITIONS

Store at temperatures not exceeding 30

Protect from light & moisture.

The expiration date refers to the product correctly stored at

the required conditions.

AVAILABILITY

Clopidogrel (NORPLAT

) 75mg film-coated tablets are available

in Alu-Alu blister packs of 7’s, box of 28 film-coated tablets.

CAUTION

Foods, Drugs, Devices and Cosmetics Act prohibits

dispensing without prescription.

Keep out of reach of children.

DESCRIPTION

Clopidogrel (NORPLAT ) is an inhibitor of ADP-induced platelet

aggregation. It reduces the chance of having a heart attack

or a stroke in people who have already had a heart attack or

a stroke.

Chemically it is methyl (+)-(S )-

-(2-ch lorop he nyl )-6, 7-

dihydrothieno[3,2-c]pyridine-5(4H)-acetate sulfate (1:1). The

molecular

formula

clopidogrel

bisulfate

ClNO

and the structural formula is:

FORMULATION

Clopidogrel (NORPLAT ) is available for oral administration

Clopidogrel (NORPLAT )

Tablets 75mg

Each film-coated tablet contains:

Clopidogrel (as bisulfate).75mg

CLINICAL PHARMACOLOGY

Mechanism of Action

Clopidogrel is an inhibitor of platelet aggregation, that is, a

drug that inhibits the ability of platelets to clump together as

part of a blood clot.

It appears to act by blocking the adenosine phosphate (ADP)

receptors, which prevents fibrinogen binding to the receptor.

This decreases the ability of platelet adhesion and aggregation.

Clopidogrel is a prodrug and requires biotransformation to

produce i

nhibition of platelet aggregation. The active metabolite

of clopidogrel also inhibits platelet aggregation induced by

agonists other than ADP by blocking the amplification of platelet

activation by released ADP.

Pharmacokinetics

Clopidogrel

after

administration

requires

h ep a tic

biotransformation to an active metabolite. Hepatic activation

is thought to be mediated by the CYP P450 1A subfamily. The

uncharacterized active metabolite is labile and highly reactiv

Absorption:

Following oral administration, clopidogrel is rapidly absorbed.

Absorption is at least 50% and is not significantly affected by

food. Peak plasma concentrations (roughly 3mg/L) of the

primary circulating metabolite occur at about one hour following

multiple dosing of 75mg/day. Plasma concentrations of the

parent drug are undetec table 2 hours after an oral dose.

Distribution:

Clopidogrel and the main circulating metabolite bind reversibly

to human plasma proteins

(98% and 94% respectiv ely).

Metabolism:

Clopidogrel is extensively metabolized in the liver.

The main

circulating metabolite is the carboxylic acid derivative, and it

has no effect on platelet aggregation. The active metabolite

appears to be thiol derivative but has not been identified in

plasma.

Elimination:

Clopidogrel and its metabolites are excreted about equally in

urine and feces. The half-life of the carboxylic acid derivative

is about 8 hours.

Special populations:

Renal Insufficiency

After repeated doses of 75mg clopidogrel per day, plasma

levels of the main circulating metabolite were lower in patients

with severe renal impair

ment (creatinine clearance from 5 to

15mL/min) compared to subj ects with moderate renal

impairment (creatinine clearance 30 to 60mL/min) or healthy

subjects. However, the prolongation of bleeding time was

similar. No dose adjustment is required in mild to moderate

renal impaired patients.

THERAPEUTIC INDICATIONS

Clopidogrel (NORPLAT ) is indicated for the reduction

of thrombotic events in patients with recent myocardial

infarcti on, recent stroke , or esta blished peripheral

arterial disease.

Clopidogrel

(NORPLAT

) is used prophylac tically in

patients at risk of thromboembolic disorders such as

myocardial infarction, peripheral arterial disease and

stroke.

Clopidogrel

(NORPLAT ) is also indicated for acute

coronary syndrome (unstable angina/non-Q-wave MI)

DOSAGE AND A

DMINISTRATION

Clopidogrel (NORPLAT ) can be administered with or without

food.

Recent MI, recent stroke,

or establ ished peripheral

arterial disease: The recommended daily dose is one

Clopidogrel

(NORPLAT

tablet

(75mg)

d ai l y .

Prophylactic use in patients at risk of thromboembolic

disorders such as MI, peripheral arterial disease and stroke:

T h e

r e c o m m e n d e d

d a i l y

d o s e

o n e

C l o p i d o g r e l (NORPLAT

) tablet (75mg)

daily .

Acut e coro nary syndrome (unsta ble angina/non-Q

wave MI): Dose should be initiated with a single

300mg loading dose and then con

tinued at 75mg

once daily (with Aspirin 75mg-325mg once daily).

ADVERSE EFFECTS

Clopidogrel is generally well tolerated. However the following

adverse

effects have been reported during trea tment.

Common: Gastrointestinal disturbances (Diarrhea, abdominal

pain, indigestion and nausea) and dermatological reactions

(rash, pruritis).

Less common: Chest pain, nose bleeds.

Rare: Gastro intesti nal bleeding, gastric

ulcers,

seve re

neutropenia or agranulocytosis, thrombocytopenia, thrombotic

thrombocytopenic purpura, aplastic anemia, membranous

nephropathy with nephrotic syndrome, loss of taste, acute

arthritis.

Please read the contents carefully before use.

This package insert is continually updated from time to time.

PH03-200007090

Manufactured by: Getz Pharma (Pvt.) Ltd., 29-30/27, K.I.A., Karachi - 74900, Pakistan.

Imported by: Getz Pharma (Phils.) Inc., 2/F Tower 1, The Rockwell Business Center, Ortigas Ave.,

Pasig City, Philippines.