Clopidogrel North star tablets

Release form

Tablets, film-coated

Composition

1 tablet contains clopidogrel hydrosulfate 97.875 mg, in terms to clopidogrel — 75 mg

auxiliary substances:starch pregelatinization. anhydrous lactose (milk sugar, anhydrous), macrogol (polyethylene glycol 6000). magnesium stearate. cellulose microcrystalline (PH 112), castor oil hydrogenated, the composition of the membrane shell:Selichot AQ–01673 (hypromellose (hydroxypropylmethylcellulose), macrogol (polyethylene glycol 400), macrogol (polyethylene glycol 6000), titanium dioxide, aluminum lacquer dye Ponceau 4 R).

Packaging

14, 28, 30, 60,28 PCs.

Pharmacological action

Clopidogrel is a specific and active inhibitor of platelet aggregation, has koronrodilatirtee action. Selectively reduces the binding of ADP receptors on platelets and activation of the receptors of the GPI Ib/IIIa by the action of ATP. attenuating platelet aggregation. Reduces agregatia platelets, caused by other agonists, preventing activation of the released ADP, does not affect the activity of phosphodiesterase (PDE). Irreversibly binds to ADP-receptors platelets, which remain impervious to the stimulation of ADP throughout the life cycle (about 7 days). Inhibition of platelet aggregation is observed 2 hours after administration (40% inhibition) initial dose of 400 mg. the Maximum effect (60% suppression of aggregation) develops after 4-7 days of admission dose 50-100 mg/day. Antiplatelet effect lasts for the entire period of life of platelets (7-10 days). In the presence of atherosclerotic lesions of the vessel prevents the development of atherothrombosis regardless of the localization of vascular process (cerebrovascular. cardiovascular or peripheral lesions).

Testimony

Prevention of thrombotic complications:

• after myocardial infarction (from a few days up to 35 days), ischaemic stroke (from 6 days to 6 months) or when diagnosed disease of peripheral arteries,
• in acute coronary syndrome without ST-segment elevation (unstable angina or myocardial infarction without pathological Q wave), including patients undergoing surgery for percutaneous coronary artery bypass grafting, in combination with acetylsalicylic acid,
• in acute coronary syndrome with ST-segment elevation (acute myocardial infarction) in combination with acetylsalicylic acid, in patients receiving drug treatment with possible use of thrombolytic therapy.

Contraindications

• hepatic insufficiency of severe degree,
• acute bleeding (for example, peptic ulcer or intracranial hemorrhage),
• pregnancy
• breastfeeding,
• the age of 18 years (safety and efficacy not established),
• hypersensitivity to the drug.With caution should designate product in the liver and kidney (i.e. with moderate hepatic and/or renal failure), trauma, preoperative conditions.

Method of application and doses

Clopidogrel is taken orally, regardless of meals. 

For prevention of coronary abnormalities in patients after myocardial infarction, ischemic stroke and diagnosed peripheral artery disease is 75 mg 1 time/day. Treatment should begin within a few days to 35 days after myocardial infarction and from 7 days to 6 months after ischemic stroke. 

In acute coronary syndrome without ST-segment elevation (unstable angina or myocardial infarction without tooth Q) treatment should begin with the appointment of a single loading dose 300 mg, then continue to use the drug in a dose 75 mg 1 times/day (with simultaneous appointment of acetylsalicylic acid at a dose 75-325 mg/day). Since the use of acetylsalicylic acid in high doses is associated with a greater risk of bleeding, the recommended dose should not exceed 100mg. the Course of treatment – up to 1 year. 

In acute myocardial infarction with ST-segment elevation the drug appoint one dose 75 mg 1 times/day using an initial loading dose in combination with acetylsalicylic acid, in combination or without thrombolytics. For patients older than 75 years, treatment with clopidogrel should be undertaken without the use of a loading dose. Combination therapy is started as early as possible after the onset of symptoms and continued for at least 4 weeks.

Side effects

The frequency of side effects is determined according to the following criteria: 

very often more than 1/10, 

often more 1/100 and less 1/10, 

infrequently – more 1/1000 and less 1/100, 

seldom more 1/10000 and less 1/1000, 

very rare – less than 1/10000, including isolated cases 

From the blood coagulation system: often – bleeding (in most cases within the first month of treatment), purpura, bruising, rarely – conjunctive hemorrhage and rarely intracranial bleeding, prolonged bleeding time, leukopenia, a decrease in the number of neutrophils and eosinophils, reduction in the number of platelets. 

With the hematopoietic system: rarely – tromboliticescoe thrombocytopenic purpura, severe thrombocytopenia (platelet count <,, 30=”” 000=”” br=””>,From the nervous system: rare – headache, dizziness, paresthesia, rarely, vertigo, rarely – confusion, hallucinations. 

Of the cardiovascular system: often- swelling, very rarely – heavy bleeding, bleeding from the operative wound, vasculitis, reduced blood pressure. 

The respiratory system: often – nasal bleeding; very rarely bronchospasm, interstitial pneumonitis, pulmonary hemorrhage, hemoptysis. 

From the digestive system: often – diarrhea, abdominal pain, dyspepsia, bleeding from the digestive tract, rarely, gastric ulcer and duodenal ulcer, gastritis, vomiting, nausea, flatulence, constipation, rarely retroperitoneal bleeding, very rarely – colitis (including ulcerative or lymphocytic), pancreatitis, changing taste sensations, stomatitis, hepatitis, acute liver failure, increased liver enzymes, 

The skeletal-muscular system: very rarely – arthralgia, arthritis, myalgia. 

From the side of urinary system: rarely – hematuria, very rarely – glomerulonephritis, gipercreatininemia. 

Dermatological reactions: very rarely – bullous rash (erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis), rash erythematous, eczema, flat lichen. 

Allergic reactions: very rarely – angioneurotic edema, urticaria, anaphylactoid reactions, serum sickness. 

Other: very rarely – increased body temperature.

Special instructions

During treatment necessary to monitor the indicators of hemostasis system (activated partial thromboplastin time (APTT), number of platelets, tests of functional activity of platelets), regularly examine the functional activity of the liver. 

Clopidogrel should be used with caution in patients with risk of severe bleeding in trauma, surgical intervention, patients receiving acetylsalicylic acid, non-steroidal anti-inflammatory drugs (including COX-2 inhibitors), heparin or inhibitors of glycoprotein IIb/IIIA. Careful monitoring of patients to detect any signs of bleeding, including hidden, especially during the first weeks of the drug and/or after invasive procedures on the heart or surgery. When planning surgical intervention, treatment with clopidogrel should be discontinued 7 days before surgery. 

Patients should be warned that stopping the bleeding will take more time than usual, so they should inform the doctor about each case of bleeding. 

Were marked by rare cases of thrombotic thrombocytopenic purpura (TTP) after receiving clopidogrel. This condition is characterized by thrombocytopenia and microangiopathic hemolytic anemia in combination with neurological symptoms, renal dysfunction or fever. The development of TTP is life threatening and requires urgent measures, including the holding of plasmapheresis. Due to insufficient amount of data, clopidogrel should not be administered in the acute period of ischemic stroke (first 7 days). The drug should be administered with caution in patients with impaired renal function. 

Clopidogrel should be administered with caution to patients with moderate liver dysfunction, which may cause hemorrhagic diathesis. 

In patients with congenital galactose intolerance, malabsorption syndrome of glucose-galactose and lactase deficiency should not take clopidogrel.

Drug interactions

The combined use of clopidogrel with warfarin is not recommended as this combination may intensify the bleeding. 

The appointment of inhibitors of glycoprotein IIb/IIIA in conjunction with clopidogrel increases the risk of bleeding. 

The use of nonsteroidal anti-inflammatory drugs in conjunction with clopidogrel increases the risk of bleeding. 

Not recommended concomitant use of clopidogrel with CYP2C19 inhibitors (e.g. omeprazole). 

Not clinically significant pharmacodynamic interaction with clopidogrel use in conjunction with atenolol, nifedipine,phenobarbital, cimetidine, estrogens, digoxin, theophylline, tolbutamide, antacids.

Overdose

Symptoms: prolonged bleeding time and subsequent complications. 

Treatment: the occurrence of bleeding should be carried out appropriate therapy. If you need a fast correction of the lengthening of bleeding time, it is recommended that the platelet transfusion. There is no specific antidote.

Storage conditions

Keep at temperature not exceeding 25 °C. Keep out of reach of children.

Shelf life

2 years.