Instruction for use: Listab 75

Dosage form: film-coated tablets

Active substance: Clopidogrelum

ATX

B01AC04 Clopidogrel

Pharmacological groups

Antiaggregants

The nosological classification (ICD-10)

I20.0 Unstable angina: heberden disease; Angina pectoris; The attack of angina pectoris; recurrent angina; Spontaneous angina; Stable angina pectoris; Angina rest; Angina progressing; Angina mixed; Angina spontaneous; stable angina; Chronic stable angina; Angina Syndrome X

I21 Acute myocardial infarction: Myocardial infarction in the acute phase; Acute Myocardial Infarction; Myocardial infarction with pathologic Q wave and without; Myocardial infarction complicated by cardiogenic shock; Infarction left ventricular; Transmural myocardial infarction; Myocardial infarction netransmuralny (subendocardial); Netransmuralny myocardial infarction; Subendocardial myocardial infarction; The acute phase of myocardial infarction; Acute myocardial infarction;Sub-acute phase of myocardial infarction; Subacute phase of myocardial infarction; Thrombosis of the coronary arteries (the arteries); Threatened myocardial infarction; Myocardial infarction without Q wave

I24.9 Acute ischemic heart disease, unspecified: Coronary heart disease; Coronary insufficiency; Acute coronary insufficiency; Acute coronary syndrome

I25.2 Transferred last myocardial infarction: Cardiac syndrome; Myocardial infarction; post-MI; Rehabilitation after myocardial infarction; Reocclusion of the operated vessel; Angina postinfarctnaya; Status after myocardial infarction; Status after myocardial infarction; myocardial infarction

I48 Atrial fibrillation and flutter: Permanent atrial tachyarrhythmias; Relief frequent ventricular rate during atrial flutter or blink; atrial fibrillation; Paroxysm of atrial fibrillation and flutter; Paroxysm of atrial fibrillation; Paroxysmal atrial fibrillation; Atrial premature beats; Tahiaritmicheskoy atrial fibrillation; Tahisistolicheskoy atrial fibrillation; auricular flutter; Life-threatening ventricular fibrillation; Atrial fibrillation; Chronic atrial fibrillation; supraventricular arrhythmia; Paroxysmal atrial fibrillation and flutter; Paroxysmal fibrilloflutter; Atrial premature beats

I49.8 Other specified cardiac arrhythmias: atrial fibrillation; Arrhythmia Paroxysmal atrial; Atrial arrhythmia tachysystolic; sinus arrhythmia; Asynergia ventricular; Asynergia left ventricle; Corrigan's pulse; atrial fibrillation; atrial tachyarrhythmia; The migration of supraventricular pacemaker; Orthostatic changes in pulse; Disclaimer sinoatrial node; The paradoxical pulse; Paroxysm of atrial fibrillation; Paroxysmal atrial fibrillation; Paroxysmal dysrhythmia; Paroxysmal atrial-ventricular rhythm; Romano-Ward syndrome; trigemini; bigeminy

I63 Cerebral infarction: ischemic Stroke; Ischemic brain disease; Ischemic stroke; Ischemic stroke and its consequences; Ischemic cerebral stroke; Ischemic cerebrovascular accident; Ischemic brain damage; Ischemic brain damage; ischemic conditions; Cerebral ischemia; Acute hypoxia brain; Acute cerebral ischemia; Acute ischemic cerebrovascular accident; Acute cerebral infarction; Acute ischemic stroke; Acute period of ischemic stroke; Focal cerebral ischemia; Ischemic stroke; recurrent stroke; The syndrome of Morgagni-Adams-Stokes; Chronic cerebral ischemia; cerebrovascular stroke; embolic stroke; Ischemic brain damage

I73.9 Peripheral vascular disease, unspecified: angiospasm; Vasospasm / vasoconstriction; vasospastic disorders; Violation of venous microcirculation; Violation of circulation; Violation of peripheral blood circulation; Lack of peripheral blood circulation in the lower and upper limbs; Peripheral arterial occlusive disease; Peripheral arterial occlusive disease in stages III-IV on Fontaine; Peripheral vascular insufficiency; Peripheral vascular lesions; Peripheral vascular disorders; Peripheral circulatory disorder; spasm of artery; angiospasm; Functional peripheral arterial disease; Chronic occlusive disease; Chronic obliterating diseases of the lower limbs; Chronic arterial occlusive disease

I74 Embolism and arterial thrombosis: Thrombosis of effort (stress); Arterial thrombosis; Arteriothrombosis; Subacute and chronic arterial thrombosis; Subacute thrombosis of peripheral arteries; Postoperative thrombosis; Vascular thrombosis; Vascular embolism; Thrombosis of aortocoronary shunt; Arterial thrombosis; Thrombosis of arteries; Coronary artery thrombosis; Coronary thrombosis; Thrombosis of blood vessels; Thrombosis with ischemic stroke; Thrombosis with general surgical operations; Thrombosis in Oncology Operations; Vascular thrombosis; Thrombus formation in the postoperative period; Thrombotic complications; Thromboembolic diseases; Thromboembolic syndrome; Thromboembolic complication in the postoperative period; Thromboembolism of arteries; Partial vascular thrombosis; Embolism; Embolism of arteries

I77.1 arteriostenosis: Occlusive arterial disease; Peripheral arterial occlusive disease;Peripheral arterial occlusive disease in stages III-IV on Fontaine

Z100 * CLASS XXII Surgical practice: Abdominal surgery; adenomectomy; Amputation; Coronary angioplasty; Angioplasty of the carotid arteries; Antiseptic skin treatment for wounds; Antiseptic Hand; Appendectomy; atherectomy; Balloon coronary angioplasty; Vaginal hysterectomy; The coronary bypass; Interventions in the vagina and cervix; Interventions on the bladder; Intervention in the mouth; Restoration and reconstructive surgery; Hand hygiene of medical personnel; Gynecologic surgery; Gynecological intervention; Gynecological surgery; Hypovolemic shock during operations; Disinfection of purulent wounds; Disinfection of wounds edges; Diagnostic intervention; Diagnostic procedures; Cervical Diathermocoagulation; Long-surgery; Replacing the fistula catheters; Infection in orthopedic surgery; Artificial heart valve; cystectomy; Short-term outpatient surgery; Short-term operation; Short surgical procedures; Krikotireotomiya; Blood loss during surgery; Bleeding during surgery and in the postoperative period; Kuldotsentez; laser photocoagulation; laser coagulation; retinal laser coagulation; Laparoscopy; Laparoscopy in Gynecology; CSF fistula; Small gynecological operations; Small surgical procedures; Mastectomy and subsequent plastic; mediastinotomy; Microsurgical operations on the ear; Mukogingivalnye operation; suturing; Minor surgery; neurosurgical operation; Immobilization of the eyeball in ophthalmic surgery; testectomy; pancreatectomy; Perikardektomiya; The period of rehabilitation after surgery; The period of convalescence after surgery; Percutaneous transluminal coronary angioplasty; Pleural thoracentesis; Pneumonia postoperative and posttraumatic; Preparation for surgical procedures; Preparation for surgery; Preparation of the surgeon's hands before surgery; Preparation of the colon for surgical procedures; Postoperative aspiration pneumonia in neurosurgical and thoracic surgery; Postoperative nausea; Postoperative bleeding; postoperative granuloma; postoperative shock; The early postoperative period; myocardial revascularization; Radiectomy; gastric Resection; bowel resection; uterine Resection; liver Resection; enterectomy; Resection of part of the stomach; Reocclusion of the operated vessel; Bonding tissues during surgical procedures; Removal of sutures; Condition after eye surgery; Condition after surgery; Condition after surgery in the nasal cavity; Condition after gastrectomy; Status after resection of the small intestine; Condition after tonsillectomy; Condition after removal of the duodenum; Condition after phlebectomy; Vascular surgery; Splenectomy; Sterilization of surgical instruments; Sterilization of surgical instruments; sternotomy; Dental surgery; Dental intervention in periodontal tissues; strumectomy; Tonsillectomy; Thoracic surgery; Thoracic surgery; total gastrectomy; Transdermal intravascular coronary angioplasty; Transurethral resection; Turbinektomiya; Removal of a tooth; cataract surgery; Removal of cysts; tonsillectomy; Removal of fibroids; Removing the mobile primary teeth; Removing polyps; Removing broken tooth; Removal of the uterus body; Removal of sutures; Fistula likvoroprovodyaschih ways; Frontoetmoidogaymorotomiya; Surgical infection; Surgical treatment of chronic limb ulcers; Surgery; The surgery in the anal area; The surgery on the colon; Surgical practice; The surgical procedure; Surgical interventions; Surgery on the gastrointestinal tract; Surgical procedures on the urinary tract; Surgical procedures on the urinary system; Surgical intervention of the genitourinary system; Surgical procedures on the heart; Surgical manipulation; surgery; Surgery on the veins; Surgical intervention; Vascular surgery; Surgical treatment of thrombosis; Surgery; cholecystectomy; Partial gastric resection; hysterectomy; Percutaneous transluminal coronary angioplasty; Percutaneous transluminal angioplasty; Coronary artery bypass; tooth Extirpation; Extirpation of milk teeth; pulpectomy; pulsative cardiopulmonary bypass; tooth Extraction; teeth Extraction; cataract extraction; Electrocoagulation; endourological intervention; episiotomy; Etmoidotomiya; Complications after tooth extraction

Composition

active substance: Clopidogrel hydrogen sulfate 98 mg

(Equivalent to 75 mg of clopidogrel)

Auxiliary substances: mannitol - 48 mg; MCC - 52.48 mg; Giprolose - 16.8 mg; Croscarmellose sodium - 7.2 mg; Silicon dioxide - 0.72 mg; Talc - 4.8 mg; Stearic acid - 12 mg

Membrane film: hypromellose - 3.88 mg; Macrogol 6000 - 0.76 mg; Titanium dioxide (E171) - 1.01 mg; Talc - 4.26 mg; Iron dye red oxide (E172) - 0.06 mg; Dimethicone - 0.03 mg

Description of dosage form

Tablets round, double radius, film-coated pale pink.

Pharmachologic effect

Mode of action - antiaggregational.

Pharmacodynamics

Inhibitor of platelet aggregation. Clopidogrel is a prodrug, one of its metabolites is an inhibitor of platelet aggregation. The active metabolite of clopidogrel selectively inhibits the binding of ADP to the platelet-derived P2Y12 receptor and subsequent ADP-mediated activation of the glycoprotein IIb / IIIa complex, leading to suppression of platelet aggregation. Due to the irreversibility of binding, platelets remain immune to stimulation of ADP for the rest of their life (about 7-10 days), and restoration of normal platelet function occurs at a rate corresponding to the rate of platelet renewal. Aggregation of platelets caused by agonists other than ADP is also inhibited by blockade of enhanced platelet activation by the released ADP. Due to the fact that the formation of the active metabolite occurs with the participation of P450 isoenzymes, some of which are polymorphic or inhibited by other drugs, adequate platelet suppression is not possible in all patients. With a daily intake of clopidogrel at a dose of 75 mg, a significant inhibition of ADP-induced platelet aggregation is noted from the first day of administration, which gradually increases for 3-7 days and then reaches a constant level (when the equilibrium state is reached). In the equilibrium state, platelet aggregation is suppressed on average by 40-60%. After stopping the use of clopidogrel, platelet aggregation and bleeding time gradually return to the baseline level on average for 5 days.

Pharmacokinetics

Suction

With a single and repeated oral administration at a dose of 75 mg / day, clopidogrel is rapidly absorbed.

After oral administration in a single dose of 75 mg, the mean Cmax of unchanged clopidogrel in the blood plasma is reached after about 45 minutes and is approximately 2.2-2.5 ng / ml. According to the excretion of metabolites of clopidogrel with urine, its absorption is approximately 50%.

Distribution

In vitro, clopidogrel and its main circulating non-active metabolite in the blood reversibly bind to plasma proteins (98 and 94%, respectively). This bond is unsaturated in a wide range of concentrations.

Metabolism

Clopidogrel is extensively metabolized in the liver. In vitro and in vivo clopidogrel is metabolized in two ways: the first through esterases and subsequent hydrolysis with the formation of an inactive derivative of carboxylic acid (85% of the circulating metabolites), the second through the isoenzymes of the cytochrome P450 system. Initially, clopidogrel is metabolized to 2-oxo-clopidogrel, which is an intermediate metabolite. Subsequent metabolism of 2-oxo-clopidogrel results in the formation of an active metabolite, the thiol clopidogrel derivative. In vitro metabolism along this pathway is carried out with the participation of isoenzymes CYP3A4, CYP2C19, CYP1A2 and CYP2B6. The active thiol clopidogrel metabolite, which was isolated in in vitro studies, quickly and irreversibly binds to platelet receptors, thus blocking platelet aggregation.

Cmax of the active metabolite of clopidogrel after receiving its loading dose of 300 mg is 2 times greater than Cmax after 4 days of receiving a maintenance dose of clopidogrel 75 mg. When taking 300 mg of clopidogrel, Cmax is reached within approximately 30-60 minutes.

Excretion

Within 120 hours after oral intake of 14C-labeled clopidogrel, about 50% of radioactivity is excreted in the urine and approximately 46% - with feces. After a single oral administration at a dose of 75 mg T1 / 2, clopidogrel is approximately 6 hours. After oral administration in a single dose and repeated doses of T1 / 2, the main circulating inactive metabolite is 8 hours.

Pharmacogenetics

With the help of the CYP2C19 isoenzyme, both an active metabolite and an intermediate metabolite, 2-oxo-clopidogrel, are formed.

The pharmacokinetics and antiplatelet effect of the active metabolite clopidogrel, when examining platelet aggregation ex vivo, vary depending on the genotype of the isoenzyme CYP2C19. The allele of the CYP2C19 * 1 gene corresponds to a fully functional metabolism, while the CYP2C19 * 2 and CYP2C19 * 3 gene alleles are non-functional. Alleles of CYP2C19 * 2 and CYP2C19 * 3 genes cause a decrease in metabolism in the majority of representatives of Caucasoid (85%) and Mongoloid races (99%). Other alleles that are associated with a lack or decrease in metabolism are less common and include, but are not limited to, the alleles of the CYP2C19 * 4, * 5, * 6, * 7, and * 8 genes. Patients with a low activity of the CYP2C19 isoenzyme should have the two alleles of the gene with loss of function indicated above. Published frequency of occurrence of phenotypes with a low activity of the isoenzyme CYP2C19 is 2% in Caucasians, 4% in the Negroid race, and 14% in the Mongoloid race. There are corresponding tests to determine the patient's genotype of the CYP2C19 isoenzyme.

Reduced CYP2C19-mediated metabolism in intermediate and low metabolizers leads to a decrease in Cmax in plasma and AUC of the active metabolite by 30-50% after loading doses of 300 or 600 mg and a maintenance dose of 75 mg. As a result of less exposure of the active metabolite, less pronounced inhibition of platelet activity or more pronounced residual platelet activity is observed.

Special patient groups

The pharmacokinetics of the active metabolite of clopidogrel in certain groups of patients has not been studied.

Elderly patients. In elderly volunteers (over 75 years old), when compared with young volunteers, differences in platelet aggregation and bleeding time were not obtained. Do not need dose adjustment for the elderly.

Children. No data available.

Impaired renal function. After repeated use of clopidogrel at a dose of 75 mg / day in patients with severe renal disease (Cl creatinine from 5 to 15 ml / min), inhibition of ADP-induced platelet aggregation was lower (25%) than that of healthy volunteers, but the lengthening of time Bleeding was similar to that of healthy volunteers who received clopidogrel at a dose of 75 mg / day.

Violation of the function of the liver. After daily, for 10 days, taking clopidogrel at a daily dose of 75 mg in patients with severe liver damage, inhibition of ADP-induced platelet aggregation was similar to that of healthy volunteers. The mean bleeding time was also comparable in both groups.

Ethnicity. The prevalence of the alleles of the CYP2C19 isoenzyme genes responsible for intermediate and decreased metabolism is different in representatives of different ethnic groups. There are very many

Indications

Prevention of atherothrombotic complications in patients with the following conditions and diseases:

Myocardial infarction (with a duration of several to 35 days), ischemic stroke (with a duration of 7 days to 6 months), diagnosed occlusive disease of peripheral arteries;

Acute coronary syndrome without ST segment elevation (unstable angina or myocardial infarction without Q wave), including patients who underwent stenting with percutaneous coronary intervention (in combination with acetylsalicylic acid - ASA);

Acute coronary syndrome with ST segment elevation (acute myocardial infarction) with drug treatment and the possibility of thrombolysis (in combination with ASA).

Prevention of atherothrombotic and thromboembolic complications, including stroke, in atrial fibrillation (atrial fibrillation):

Atrial fibrillation (atrial fibrillation) in patients who have at least one risk factor for vascular complications, cannot take indirect anticoagulants and have a low risk of bleeding (in combination with ASA).

Contraindications

Hypersensitivity to any component of the drug;

Severe hepatic impairment;

Acute bleeding (eg, peptic ulcer or intracranial hemorrhage);

pregnancy;

Lactation period;

Age to 18 years (safety of use not established).

With caution: liver and kidney disease (moderate hepatic and / or renal failure); Pathological conditions that increase the risk of bleeding, incl. With injuries and operations; Simultaneous administration of NSAID (including COX-2 inhibitors), incl. ASA, heparin and glycoprotein IIb / IIIa inhibitors.

Pregnancy and breast-feeding

In animal experiments it has been shown that clopidogrel and its metabolites penetrate into breast milk, do not affect fertility and do not exert a toxic effect on the fetus. However, in the absence of sufficient safety data, it is not recommended to use the drug in pregnant and lactating women.

Side effects

When receiving therapeutic doses, the drug is usually well tolerated.

Frequency of development of side effects: often (1-10%); Infrequently (0.1-1%); Rarely (0.01-0.1%); Very rarely (less than 0.01%, including individual reports).

From the blood and organs of hematopoiesis: infrequently - thrombocytopenia, leukopenia, neutropenia and eosinophilia; Very rarely - cases of serious bleeding, mainly in subcutaneous fatty tissue, muscles and joints, eye hemorrhages (conjunctival, in the tissue and retina of the eye), nosebleeds, bleeding from the respiratory system, postoperative wounds, cases of bleeding with death (mainly Intracranial, gastrointestinal and retroperitoneal); Very rarely - agranulocytosis, aplastic anemia / pancytopenia, thrombotic thrombocytopenic purpura (TTP).

From the side of the immune system: very rarely - anaphylactoid reactions (including angioedema, urticaria), maculopapular or erythematous rash, serum sickness, bullous dermatitis (toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme).

From the nervous system: infrequently - headache, dizziness, paresthesia; Rarely - vertigo; Very rarely - confusion, hallucinations, changes in taste.

From the CCC: very rarely - vasculitis, lowering blood pressure.

From the respiratory system: very rarely - bronchospasm, interstitial pneumonitis.

On the part of the digestive system: often - diarrhea, abdominal pain, dyspepsia; Infrequently - ulcers of the stomach and duodenum, gastritis, vomiting, nausea, constipation, flatulence; Very rarely - pancreatitis, colitis (including ulcer or lymphocytic), stomatitis, acute liver failure, hepatitis (non-infectious).

From the skin: very rarely - eczema and flat lichen.

From the musculoskeletal system: very rarely - arthralgia, arthritis, myalgia.

From the genitourinary system: infrequently - hematuria; Very rarely glomerulonephritis.

Laboratory indicators: infrequent - prolongation of bleeding time; Very rarely - an increase in the activity of hepatic transaminases, an increase in the concentration of serum creatinine.

Other: very rarely - fever.

Interaction

Oral anticoagulants: simultaneous use of clopidogrel with oral anticoagulants is not recommended, because. This combination may increase bleeding. Despite the fact that taking 75 mg / day clopidogrel did not change the pharmacokinetics of S-warfarin and INR in patients who had been taking warfarin for a long time, the simultaneous use of clopidogrel and warfarin increases the risk of bleeding due to the effects that both drugs exert on haemostasis.

Inhibitors of glycoprotein IIb / IIIa: clopidogrel should be used with caution in patients who simultaneously receive glycoprotein IIb / IIIa inhibitors.

ASA: does not alter clopidogrel-induced platelet aggregation inhibition induced by ADP, but clopidogrel enhances the effect of ASA on platelet aggregation induced by collagen. Nevertheless, simultaneous administration of ASA 500 mg twice daily for 24 hours did not cause a significant increase in bleeding time due to the use of clopidogrel. Between clopidogrel and ASA, pharmacodynamic interaction is possible, which leads to an increased risk of bleeding. Consequently, the simultaneous use of these drugs should be carried out with caution. Nevertheless, clopidogrel and ASA were prescribed together for up to one year.

Heparin: clopidogrel did not require a change in the dose of heparin or did not affect the effect of heparin on blood coagulation. Simultaneous use of heparin did not affect the inhibition of platelet aggregation caused by clopidogrel. Between clopidogrel and heparin, pharmacodynamic interaction is possible, which leads to an increased risk of bleeding. Consequently, the simultaneous use of these drugs should be done with caution.

Thrombolytic drugs: the safety of the combined use of clopidogrel with fibrin-specific and fibrin-specific thrombolytic agents and heparins was investigated in patients with acute myocardial infarction. The frequency of clinically significant bleeding was similar to that observed with the use of thrombolytic agents and heparin in conjunction with ASA.

NSAID: the combined use of clopidogrel and naproxen increased latent blood loss from the gastrointestinal tract. However, due to the lack of sufficient clinical studies on interactions with other NSAIDs, it is currently unclear whether the increased risk of gastrointestinal bleeding is common to all NSAIDs. Consequently, the simultaneous use of NSAIDs (including inhibitors of COX-2) and clopidogrel requires caution.

Another concomitant therapy: since clopidogrel is metabolized to its active metabolite in part by CYP2C19, it is expected that the use of drugs that suppress the activity of this enzyme will lead to a decrease in drug concentrations of the active metabolite of clopidogrel. As a precautionary measure, the simultaneous use of drugs that suppress CYP2C19 should be avoided.

Drugs suppressing CYP2C19 include omeprazole and esomeprazole, fluvoxamine, fluoxetine, moclobemide, voriconazole, fluconazole, ticlopidine, ciprofloxacin, cimetidine, carbamazepine, oxcarbazepine, and chloramphenicol.

Proton pump inhibitors: omeprazole 80 mg once daily, taken either concomitantly with clopidogrel or with a 12-hour interval between doses of two drugs, reduced the exposure of the active metabolite by 45% (loading dose) and 40% (maintenance dose ). The decrease was associated with 39% (loading dose) and 21% (maintenance dose) of a decrease in platelet aggregation inhibition. It is expected that esomeprazole, taken concomitantly with clopidogrel, will also lead to a decrease in the exposure of the active metabolite.

As a precaution, do not use omeprazole or esomeprazole simultaneously with clopidogrel. Less pronounced decrease in metabolite exposure was observed in the case of pantoprazole and lansoprazole. Plasma concentrations of the active metabolite were reduced by 20% (loading dose) and by 14% (maintenance dose) during treatment with pantoprazole at a dose of 80 mg once a day. This was accompanied by a decrease in the average inhibition of platelet aggregation by 15 and 11%, respectively. These results mean that clopidogrel can be used together with pantoprazole.

Evidence that other gastric acid-lowering medications, such as histamine H2 receptor blockers (with the exception of cimetidine, which is an inhibitor of CYP2C19), and antacids, affect the antiplatelet activity of clopidogrel, no.

Other medications

Clinically important pharmacodynamic interaction was not observed when clopidogrel was used in conjunction with atenolol or nifedipine or with both of these substances.

Simultaneous use of phenobarbital or estrogen had no significant effect on the pharmacodynamic activity of clopidogrel.

The pharmacokinetics of digoxin and theophylline did not change with the simultaneous use of clopidogrel.

Antacids did not change the degree of absorption of clopidogrel.

Phenytoin and tolbutamide, which are metabolized by CYP2C9, can be safely used simultaneously with clopidogrel.

Dosing and Administration

Inside, regardless of food intake.

Adults and elderly patients with normal activity of the isoenzyme CYP2C19

Myocardial infarction, ischemic stroke and diagnosed occlusive disease of peripheral arteries: Listab® 75 is prescribed in a dose of 75 mg once a day.

Acute coronary syndrome without ST segment elevation (unstable angina, myocardial infarction without Q wave): treatment with Listab® 75 should be started with a single 300 mg loading dose and then continued at a dose of 75 mg once a day (in combination with ASA in Doses of 75-325 mg / day). Since the use of ASA at higher doses is associated with an increased risk of bleeding, the recommended dose for ASA is not more than 100 mg. The optimal duration of treatment is not officially defined. Clinical trials support the administration of the drug to 12 months, and the maximum favorable effect was observed by the 3rd month of treatment.

Acute coronary syndrome with ST-segment elevation (acute myocardial infarction with ST-segment elevation): Listab® 75 is given once in a dose of 75 mg once a day with the initial single dose loading in combination with ASA and thrombolytic agents or without combination with thrombolytics. In patients older than 75 years, treatment with the drug should begin without taking a loading dose. Combination therapy is started as soon as possible after the onset of symptoms and lasts for at least 4 weeks. The effectiveness of the use of a combination of clopidogrel and ASA with this indication over 4 weeks has not been studied.

Atrial fibrillation (atrial fibrillation): Listab® 75 is prescribed once a day at a dose of 75 mg. In combination with clopidogrel, you should start and then continue taking 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 the following doses should be taken at the usual time. If more than 12 hours have passed after missing the next dose, the patient should take the next dose at the usual time (do not take a double dose).

Special patient groups

Violation of the function of the liver. Caution should be given to the drug for liver disease (including with moderate hepatic insufficiency, which may predispose to bleeding (limited clinical experience) .It is contraindicated in patients with severe hepatic impairment.

Impaired renal function. With caution should prescribe the drug for kidney disease (including with moderate renal failure).

Elderly patients. In patients older than 75 years, Listab® 75 should be treated without taking a loading dose.

Children. The use of the drug is contraindicated in children under 18 years of age (safety and efficacy not established).

Overdose

Symptoms: with a single oral dose of 1050 mg clopidogrel (14 tablets to 75 mg), no adverse events and the need for special therapeutic measures were noted. With a single oral dose of 600 mg clopidogrel (8 tablets to 75 mg) by healthy volunteers, no side effects were noted. The increase in bleeding time corresponded to the value recorded after taking a therapeutic dose (75 mg / day).

Treatment: if necessary to quickly correct the increased bleeding time, a transfusion of platelet mass is recommended. The specific antidote of the drug is unknown.

Special instructions

Bleeding and hematologic disorders

Because of the risk of bleeding and hematologic adverse reactions during treatment, if clinical symptoms that indicate bleeding are present, a general blood test and / or other appropriate tests should be performed immediately. As with other antiplatelet agents, clopidogrel should be used with caution in patients who may be at risk for severe bleeding due to trauma, surgical or other pathological conditions, as well as those on treatment with ASA, heparin, glycoprotein IIb / IIIa inhibitors or NSAIDs , Including COX-2 inhibitors. Patients should be carefully monitored for any signs of bleeding, including concealed bleeding, especially in the first weeks of treatment and / or after invasive procedures at the heart or surgical intervention. The simultaneous use of clopidogrel with oral anticoagulants is not recommended. This can increase bleeding.

If the patient has to undergo elective surgery, and the antiplatelet effect is temporarily undesirable, the use of clopidogrel should be discontinued 7 days before the operation. Before any planned operation and taking any new drug, patients should warn therapists and dentists that they are taking clopidogrel.

Clopidogrel prolongs bleeding time and should be used with caution in patients with pathological changes predisposing to bleeding (especially the gastrointestinal and intraocular).

Patients should be informed that taking clopidogrel (alone or in combination with ASA) to stop bleeding may take longer, and that they should be notified to their doctor if they experience an unintended bleeding (localized or prolonged).

TTP

Very rarely after the use of clopidogrel, and sometimes after a short exposure, there were cases of TTP. It is characterized by thrombocytopenia and microangiopathic hemolytic anemia accompanied by neurologic changes, renal dysfunction or fever. TTP is a life-threatening condition requiring immediate treatment, including plasmapheresis.

Acute ischemic stroke

Due to the lack of data, Listab® 75 cannot be recommended in the first 7 days after an acute ischemic stroke.

During the treatment it is necessary to monitor the functional activity of the liver. With severe liver damage, the risk of developing hemorrhagic diathesis should be considered.

Influence on the ability to drive vehicles and work with machinery. Listab® 75 does not significantly affect the ability to drive vehicles or engage in other potentially hazardous activities.

Release Form

Tablets, film-coated, 75 mg. In the contour cellular packing 10 pcs. 1, 2, 3, 6 or 9 contour mesh packages in a pack of cardboard. In the contour cellular packing 14 pcs. 1 or 2 contour squares in a pack of cardboard.

Manufacturer

1. REPLECK FARM Ltd. Skopje. Republic of Macedonia, Kozle, No. 188, 1000, Skopje.

2. ZAO "FarmFirma Soteks". 141345, Russia, Moscow region, Sergievo-Posadsky municipal district, rural settlement Bereznyakovskoe, pos. Belikovo, 11.

The owner of the registration certificate: ZAO "FarmSirma" Soteks ".

The claims of consumers should be sent to the address of the manufacturer of ZAO "FarmFirma Soteks".

Conditions of supply of pharmacies

On prescription.

Storage conditions of the drug Listab 75

In dry, the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

The shelf life of the drug Listab 75

3 years.

Do not use beyond the expiration date printed on the package.