Egitromb - instructions for use, dose, side effects, contraindications

Excipients: silicon microcrystalline cellulose 198.2 mg (microcrystalline cellulose 194,236, silicon dioxide colloidal anhydrous 3,964), giprolose (with a low degree of substitution (L-HPC B1)) 12 mg, hydrogenated castor oil 12 mg, opadrai white Y-I-7000 10 mg (hypromellose 6.25 mg, titanium dioxide 3.125, macrogol-400 0.625 mg).

Description:

White or almost white round biconvex tablets covered with a film sheath, engraved with "E 181" on one side of the tablet, without or almost no odor.

Pharmacotherapeutic group:antiplatelet agent

ATX: & nbsp

B.01.A. C.04 Clopidogrel

Pharmacodynamics:

Antiaggregant agent. Specific and active inhibitor of platelet aggregation. Selectively reduces the binding of adenosine diphosphate (ADP) to receptors on platelets and activation of receptors GP IIb/IIIa under the action of ADP, thereby weakening the aggregation of platelets.

Reduces platelet aggregation, caused by other agonists, preventing their activation by released ADP, does not affect the activity of phosphodiesterase (PDE). Irreversibly binds to the platelet ADP receptors that remain impervious to ADP stimulation throughout the life cycle (about 7 days).

The inhibition of platelet aggregation is observed after 2 hours after administration (40% inhibition) of the initial dose. The maximum effect (60% suppression of aggregation) develops after 4-7 days of constant admission in a dose of 50-100 mg / day.Antiaggregant effect persists throughout the life span of platelets (7-10 days).

In the presence of an atherosclerotic lesion, the vessel interferes with the development of atherothrombosis regardless of the localization of the vascular process (cerebrovascular, cardiovascular or peripheral lesions).

Pharmacokinetics:

Clopidogrel is rapidly absorbed after repeated administration of 75 mg per day. Bioavailability is high. However, the concentration of the starting material in the plasma is low and after 2 hours does not reach the measurement limit (0.025 μg / l). The connection with plasma proteins is 98-94%. Metabolised in the liver. The main metabolite is an inactive derivative of carboxylic acid, TS_mOh which after repeated oral doses of 75 mg is achieved after 1 h (C_mOh - about 3 mg / l).

It is excreted by the kidneys - 50% and through the intestine with a fecal mass - 46% (within 120 hours after administration).

T_1/2the main metabolite after a single and repeated intake - 8 h.

The concentration of kidney metabolites is 50%.

The concentration of the main metabolite in the plasma after taking 75 mg / day is lower in patients with severe kidney disease (QC 5-15 ml / min) compared with patients with moderate kidney disease (QC from 30 to 60 ml / min) and healthy individuals.

Indications:

Prevention of atherothrombotic complications in adult patients with myocardial infarction (with a duration of several days to 35 days), ischemic stroke (with a duration of 7 days to 6 months) or with diagnosed occlusive disease of peripheral arteries.

For the prevention of atherothrombotic complications in adult patients with acute coronary syndrome in combination with acetylsalicylic acid (ASA): with the elevation of the ST segment with the possibility of carrying out thrombolytic therapy; without ST segment elevation (unstable angina, myocardial infarction without Q-wave), incl. in patients undergoing stenting with percutaneous coronary intervention.

Prevention of atherothrombotic and thromboembolic complications, including stroke, with atrial fibrillation. In adults with atrial fibrillation who have at least one risk factor for vascular complications who can not take indirect anticoagulants and have a low risk of bleeding (in combination with acetylsalicylic acid (ASA)).

Contraindications:

- Hypersensitivity to the active or any auxiliary component of the drug;

severe hepatic impairment;

- active bleeding (including bleeding from peptic ulcers or intracranial hemorrhage);

- pregnancy and lactation period (see the section "Pregnancy and lactation period");

- age under 18 years (effectiveness and safety not proven).

Carefully:

- Moderate hepatic impairment;

- CRF;

- pathological conditions that increase the risk of bleeding (including trauma, surgery), simultaneous administration of ASA, NSAIDs (including COX-2 inhibitors), warfarin, heparin and glycoprotein IIb / IIIa inhibitors;

- low activity of the isoenzyme CYP2C19 (as in such patients, when using clopidogrel in recommended doses, less active metabolite of clopidogrel is formed and its antiplatelet effect is less pronounced, and therefore, when taking the usually recommended doses of clopidogrel in acute coronary syndrome or percutaneous coronary intervention, a higher frequency of cardiovascular complications than in patients with normal activity of the isoenzyme CYP2C19).

Pregnancy and lactation:

Due to the lack of clinical data for the use of the drug in pregnant women should not be appointed clopidogrel during pregnancy.

Information on the allocation of human milk in breast milk is not, therefore, the use of the drug during lactation is contraindicated.

Dosing and Administration:

Adult and elderly patients, EGITROMB should be taken orally 75 mg once a day, regardless of food intake.

Treatment should be started in the period from several days to 35 days in patients after myocardial infarction and from 7 days to 6 months - in patients after ischemic stroke.

In acute coronary syndrome without ST segment elevation (unstable angina or myocardial infarction without Q-wave) The drug EGITROMB should be started with a single loading dose of 300 mg, and then continue taking 75 mg once a day in combination with acetylsalicylic acid (ASA 75-325 mg per day). Since higher doses of ASA are associated with an increased risk of bleeding, it is recommended to prescribe it at doses not exceeding 100 mg. Data from clinical studies indicate the possibility of using the drug EGITROMB up to 12 months, and the maximum effect of therapy is noted by 3 months.

Acute myocardial infarction with ST segment elevation: EGITROMB should be taken 75 mg once a day; Treatment should be started with a loading dose and combined with the administration of ASA and thrombolytic agents or without thrombolytics.The effectiveness of therapy for more than 4 weeks has not been studied.

Atrial fibrillation: EGITROMB should be taken once a day at a dose of 75 mg. In combination with the preparation EGITROMB it is necessary to start and then continue the administration of ASA (75-100 mg / day).

Skipping the next dose:

- if less than 12 hours have passed after missing the next dose, the missed dose of the drug should be taken immediately, and then taken at the usual time in the following doses;

- if more than 12 hours pass after missed the next dose, the patient should take the next dose at the usual time (do not take a double dose).

Special patient groups

Patients with genetically determined reduced activity of the isoenzyme CYP2C19

The low activity of the isoenzyme CYP2C19 is associated with a decrease in the antiplatelet effect of clopidogrel. The mode of application of higher doses (600 mg - loading dose, then 150 mg once a day daily) in patients with low activity of the isoenzyme CYP2C19 increases the antiplatelet effect of clopidogrel. However, at the present time in clinical studies that take into account clinical outcomes, the optimal dosage regimen of clopidogrel has not been established for patients with its reduced metabolism due to the genetically caused low activity of the CYP2C19 isoenzyme.

Elderly people

Do not require dose adjustment for the elderly.

Children

There is no experience of using the drug in children.

Patients with impaired renal function

The experience of using in patients with impaired renal function is limited.

Patients with impaired hepatic function

The experience of using in patients with liver diseases of moderate severity (in which there may be manifestations of hemorrhagic diathesis) is limited.

Side effects:

Bleeding is the most frequent reaction, most often it occurs during the first month of taking the drug. Cases of severe bleeding have been reported in patients taking clopidogrel simultaneously with acetylsalicylic acid or clopidogrel with acetylsalicylic acid and heparin (see section "Special instructions").

The frequency of side effects is determined according to the following definitions: frequent (> 1/100 - <1/10), infrequent (> 1/1 000 - <1/100) and rare (> 1/10 000 - <1/1000). "Very rare" corresponds to <1/10 000. Within each class of frequencies, undesirable effects are presented in order of decreasing severity.

From the central nervous system: infrequent: headache,dizziness and paresthesia; rare: systemic dizziness; very rarely: confusion, hallucinations, eating disorders.

From the gastrointestinal tract: frequent: gastrointestinal bleeding, diarrhea, abdominal pain, indigestion; infrequent: hemorrhagic stroke, stomach ulcer, duodenal ulcer, gastritis, nausea, vomiting, constipation, bloating; very rarely: pancreatitis, colitis (including ulcerative or lymphocytic colitis), stomatitis, acute hepatic insufficiency, hepatitis.

From the cardiovascular system and hematopoiesis system: frequent: hematoma; infrequent: increased bleeding time and reduced platelet count (thrombocytopenia), leukopenia, neutropenia and eosinophilia; very rarely: vasculitis, hypotension, thrombotic thrombocytopenic purpura (TTP) (1/200 000 patients taking the drug) (see section "Special instructions"), severe thrombocytopenia (platelet count <30x10⁹/ l), agranulocytosis, granulocytopenia, aplastic anemia / pancytopenia, anemia.

From the skin: infrequent: allergic reactions (skin rash), skin itching; very rarely: angioedema,bullous dermatitis (erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis), erythematous rash, urticaria, eczema and flatulence.

On the part of the respiratory system: very rarely: bronchospasm, interstitial pneumonitis.

Other: very rare: arthralgia, arthritis, myalgia, anaphylactoid reactions, serum sickness, fever, functional liver problems, increased blood creatinine, glomerulonephritis.

Overdose:

An overdose of clopidogrel may prolong bleeding time and lead to complications associated with bleeding. If bleeding is detected, appropriate treatment should be prescribed.

Antidotes of pharmacological activity of clopidogrel have not been found. If it is necessary to quickly shorten the extended bleeding time, platelet transfusion can eliminate the effects of clopidogrel.

Interaction:

Strengthens the antiplatelet effect acetylsalicylic acid, heparin, thrombolytics, indirect anticoagulants, non-steroidal anti-inflammatory drugs (NSAIDs), including COX-2 inhibitors , increases the risk of bleeding from the gastrointestinal tract, so the simultaneous use of these tools requires caution.

Clopidogrel should be used with caution in patients who may have a risk of increased bleeding in trauma or surgery if they are taking glyboprotein IIb / IIIa inhibitors concomitantly.

Simultaneous use of clopidogrel and warfarin is not recommended, as it may increase bleeding (see also the "Special instructions" section).

There were no clinically significant pharmacodynamic interactions in cases of simultaneous use of clopidogrel with atenolol, nifedipine or a combination of atenolol with nifedipine.

In addition, the pharmacodynamic activity of clopidogrel did not change significantly when applied phenobarbital, cimetidine or estrogens.

Pharmacokinetics digoxin or theophylline did not change with the simultaneous administration of clopidogrel.

Antacid preparations do not affect the absorption of clopidogrel.

The study of human hepatic microsomes showed that the clopidogrel metabolite, related to carboxylic acids, can suppress the activity of the CYP2C9 isoenzyme.This can increase plasma concentrations of such drugs as phenytoin, tolbutamide and NSAIDs, which are metabolized by the CYP2C9 isoenzyme. Phenytoin and tolbutamide can safely be used in conjunction with clopidogrel.

As clopidogrel metabolized to the formation of its active metabolite in part by means of the CYP2C19 system, the use of drugs inhibiting this system can lead to a decrease in the concentration of the active metabolite of clopidogrel.

The simultaneous use of strong or moderate inhibitors isoenzyme CYP2C19 (e.g., omeprazole). If proton pump inhibitors are to be taken concomitantly with clopidogrel, a proton pump inhibitor with the least inhibition of the CYP2C19 isoenzyme, such as pantoprazole.

Special instructions:

During the treatment period, it is necessary to monitor the parameters of the hemostasis system (APTT, platelet count, platelet functional activity tests); regularly investigate the functional activity of the liver.

Clopidogrel should be used with caution in patients with a risk of increased bleeding in trauma, surgery,in patients with lesions prone to bleeding (especially gastrointestinal and intraocular), as well as in patients receiving ASA, non-steroidal anti-inflammatory drugs (including COX-2 inhibitors), heparin or glycoprotein inhibitors IIb/IIIa. Patients should be carefully monitored to detect any signs of bleeding, including latent, especially during the first weeks of the drug and / or after invasive procedures on the heart or surgical procedures. The simultaneous use of clopidogrel and warfarin is not recommended, as it can increase bleeding.

In the case of surgical interventions, if antiaggregant effect is undesirable, the course of treatment should be discontinued 7 days before the operation.

Patients should be warned that, since a stoppage of bleeding that occurs when the clopidogrel is used (in combination with or without ASA) requires more time, they should inform the doctor about every case of unusual bleeding. Patients should also inform the doctor about taking the drug if they are to be treated promptly before taking any new drug.

After taking clopidogrel, thrombotic thrombocytopenic purpura (TTP) was detected very rarely, sometimes after short-term use. This condition is characterized by thrombocytopenia and microangiopathic hemolytic anemia in combination with neurological signs, impaired renal function or fever. TTP is a potentially fatal condition requiring immediate treatment, including with the use of plasmapheresis.

Due to lack of data clopidogrel It can not be recommended for acute (less than 7 days) ischemic stroke.

The experience of using clopidogrel in patients with impaired renal function is limited, so these patients clopidogrel should be administered with caution.

In case of severe violations of liver function, one should remember about the risk of hemorrhagic diathesis development, the experience of using the drug in patients with moderate liver dysfunction is limited, therefore, these patients clopidogrel should be administered with caution.

Effect on the ability to drive transp. cf. and fur:

Clopidogrel does not influence or slightly affect the ability to drive vehicles and work with machinery.

Form release / dosage:

Tablets coated with a film coating, 75 mg.

Packaging:

7 tablets blister from the combined film "cold"(polyamide / aluminum foil / PVC) / aluminum foil).

For 2 or 4 blisters in a pack of cardboard along with instructions for use.

Storage conditions:Store at a temperature not exceeding 25 ° C in a place inaccessible to children.

Shelf life:

5 years.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LSR-001128/09

Date of registration:16.02.2009

The owner of the registration certificate:Egis Pharmaceutical Plant OJSCEgis Pharmaceutical Plant OJSC Hungary

Manufacturer: & nbsp

EGIS PHARMACEUTICALS, Plc Hungary

Representation: & nbspEGIS ZAO Pharmaceutical Plant EGIS ZAO Pharmaceutical Plant Hungary

Information update date: & nbsp07.08.2015

Illustrated instructions

Instructions

Egitromb (Egitromb)