Lopirel: instructions for use, price, analogues, reviews. Indications for use

Pharmacodynamics and pharmacokinetics

The active component of the drug selectively inhibits the binding of the ADP to receptors located on the surface of platelets . Thus, activation of the GPIIb/IIIa and platelet aggregation becomes impossible. Clopidogrel also inhibits aggregation processes induced by other antagonists . Until the end of their life cycle, platelets remain damaged and incapable of aggregation .

After the first batch of medicine arrives, the antithrombotic process begins to occur, the level of leukocytes is established by the 3-7th day of administration. On average, 5 days after cessation of treatment, platelet aggregation and bleeding duration return to initial levels.

The medicine is absorbed quite quickly into the gastrointestinal tract . However, the concentration of clopidogrel in plasma is very low, absorption is 50%. The drug binds well to blood plasma proteins.

Clopidogrel is metabolized in the liver, about 80% of metabolites found in plasma are inactive. The active metabolite, which has the necessary antiaggregate effect, is formed through an oxidation reaction involving the cytochrome P450 isoenzyme 2B6 and 3A4 . The metabolite itself quickly reacts with platelets and is not detected in blood plasma.

The half-life is 6 hours for the active substance and 8 hours for its inactive metabolite. Products are excreted mainly in urine and feces.

In persons suffering from severe renal failure, a 25% decrease in the effectiveness of the drug was observed compared to healthy people.

Lopirel, 75 mg, film-coated tablets, 28 pcs.

Suction

After a single dose and during a course of oral administration at a dose of 75 mg/day, clopidogrel is rapidly absorbed. The average maximum plasma concentration (Cmax) of unchanged clopidogrel is about 2.2–2.5 ng/ml and is reached approximately 45 minutes after administration. According to the excretion of clopidogrel metabolites by the kidneys, its absorption is at least 50%.

Distribution

In vitro

clopidogrel and its main inactive metabolite circulating in the blood are reversibly bound to plasma proteins by 98% and 94%, respectively.
In vitro
, this bond is unsaturable over 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 carboxylic acid derivative (85%) from metabolites circulating in the systemic circulation, and the second way - through the cytochrome P450 system.
Initially, clopidogrel is metabolized to 2‑oxoclopidogrel, which is an intermediate metabolite. Subsequent metabolism of 2‑oxoclopidogrel leads to the formation of the active metabolite of clopidogrel, a thiol derivative of clopidogrel. In vitro,
this metabolic pathway occurs with the participation of the isoenzymes CYP3A4, CYP2C19, CYP1A2 and CYP2B6.
in vitro
studies , rapidly and irreversibly binds to platelet receptors, thereby inhibiting platelet aggregation.

With a single dose of clopidogrel in a loading dose of 300 mg, the Cmax of the active metabolite is 2 times higher than the Cmax when taking clopidogrel in a maintenance dose of 75 mg for 4 days. Cmax of the active metabolite is reached 30–60 minutes after taking clopidogrel.

Removal

Within 120 hours after human ingestion of 14C-labeled clopidogrel, approximately 50% of the radioactivity is excreted through the kidneys and approximately 46% of the radioactivity through the intestines. After a single oral dose of 75 mg, the half-life (T1/2) of clopidogrel is about 6 hours. After a single dose and repeated doses, T1/2 of the main inactive metabolite circulating in the blood is 8 hours.

Pharmacogenetics

With the help of the CYP2C19 isoenzyme, both the active metabolite and the intermediate metabolite, 2-oxoclopidogrel, are formed. Pharmacokinetics and antiplatelet effect of the active metabolite of clopidogrel, in an ex vivo

, vary depending on the genotype of the CYP2C19 isoenzyme.

The allele of the CYP2C19*1 gene corresponds to a fully functional metabolism, while the alleles of the CYP2C19*2 and CYP2C19*3 genes are non-functional. Alleles of the CYP2C19*2 and CYP2C19*3 genes are the cause of decreased metabolism in the majority of representatives of the Caucasian (85%) and Mongoloid races (99%). Other alleles associated with absent or decreased metabolism are less common and include, but are not limited to, the CYP2C19*4, *5, *6, *7, and *8 alleles. Patients who are poor metabolizers must have the two loss-of-function gene alleles listed above. Published frequencies of CYP2C19 poor metabolizer phenotypes are 2% in Caucasians, 4% in Blacks, and 14% in Chinese.

In a crossover study conducted on 40 volunteers, 10 people in each group with four subtypes of the CYP2C19 isoenzyme (ultrarapid metabolizers, extensive metabolizers, intermediate metabolizers, poor metabolizers), the pharmacokinetics and antiplatelet effect of clopidogrel at a dose of 300 mg followed by its administration were assessed. 75 mg/day and when taking clopidogrel at a dose of 600 mg followed by 150 mg/day for 5 days (reaching an equilibrium state). There were no significant differences in active metabolite exposure and mean platelet aggregation inhibition (API) (ADP-induced) values between ultrarapid, extensive, and intermediate metabolizers. In poor metabolizers, exposure to the active metabolite was reduced by 63–71% compared with extensive metabolizers. When using the 300 mg/75 mg treatment regimen in poor metabolizers, the antiplatelet effect was reduced with average IAT values of 24% (at 24 hours) and 37% (at 5 days of treatment) compared with IAT of 39% (at 24 hours). and 58% (on day 5 of treatment) in extensive metabolizers and 37% (after 24 hours) and 60% (on day 5 of treatment) in intermediate metabolizers. When poor metabolizers received the 600 mg/150 mg regimen, exposure to the active metabolite was higher than when receiving the 300 mg/75 mg regimen. In addition, the IAT was 32% (at 24 hours) and 61% (at day 5 of treatment), which was greater than that of poor metabolizers receiving the 300 mg/75 mg regimen and was similar to that in groups of patients with higher CYP2C19 intensity -metabolism, receiving a treatment regimen of 300 mg/75 mg. However, clinical outcome studies have not yet established a clopidogrel dosing regimen for patients in this group.

Consistent with the results of this study, a meta-analysis of six studies that included data from 335 volunteers treated with clopidogrel at steady state found that intermediate metabolizers reduced active metabolite exposure by 28% and poor metabolizers reduced exposure to the active metabolite by 72%. %, although IAT was reduced compared to extensive metabolizers with differences in IAT being 5.9% and 21.4%, respectively.

The effect of CYP2C19 genotype on clinical outcomes in patients treated with clopidogrel has not been assessed in prospective, randomized, controlled studies. However, few retrospective analyzes are currently available. Genotyping results are available from the following clinical studies: CURE (n=2721), CHARISMA (n=2428), CLARITY‑TIMI 28 (n=227), TRITON-TIMI 38 (n=1477) and ACTIVE-A (n=601) , as well as in several published cohort studies.

In the TRITON-TIMI 38 study and 3 cohort studies (Collet, Sibbing, Giusti), patients in the combination group who were intermediate or poor metabolizers had a higher incidence of cardiovascular events (death, myocardial infarction, and stroke) or stent thrombosis compared with those of intensive metabolizers. metabolizers.

In the CHARISMA study and one cohort study (Simon), an increase in the incidence of cardiovascular events was observed only in poor metabolizers (when compared with extensive metabolizers).

In the CURE, CLARITY, ACTIVE-A and one of the cohort studies (Trenk), there was no increase in the incidence of cardiovascular events depending on the intensity of CYP2C19 metabolism.

Clinical studies to date have not had a sufficient sample size to detect differences in clinical outcome in patients with low CYP2C19 activity.

Pharmacokinetics in special clinical situations

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

In elderly volunteers (over 75 years of age), when compared with young volunteers, there were no differences in platelet aggregation and bleeding time. No dose adjustment is required in elderly patients.

The pharmacokinetics of clopidogrel in children has not been studied.

In patients with severe kidney damage (creatinine clearance (CC) 5–15 ml/min) after repeated doses of clopidogrel at a dose of 75 mg/day, the initiation of ADP-induced platelet aggregation was lower (25%) compared with that in healthy volunteers, however the prolongation of bleeding time was similar to that in healthy volunteers receiving clopidogrel 75 mg/day. Clopidogrel was well tolerated in all patients.

In patients with severe liver damage, after daily administration of clopidogrel 75 mg/day for 10 days, the inhibition of ADP-induced platelet aggregation was similar to that in healthy volunteers. The mean bleeding time was also comparable in both groups.

The prevalence of alleles of the CYP2C9 isoenzyme genes responsible for intermediate and reduced metabolism differs among representatives of different racial groups. There is very little literature data among representatives of the Mongoloid race, which does not allow us to assess the significance of genotyping of the CYP2C19 isoenzyme for the development of ischemic complications.

Indications for use of Lopirel

The drug is used to prevent arterial thrombosis in people suffering from acute coronary syndrome:

for unstable angina ;
with myocardial infarction (without Q wave );
after acute myocardial infarction .

Also indicated for use are atherothrombotic complications in patients who have suffered a myocardial infarction , stroke , or have peripheral arterial occlusive disease . In this case, the medicine is used as a prophylaxis.

Contraindications

The drug is not prescribed:

with severe liver failure ;
pregnant and breastfeeding women;
with hemorrhagic syndrome ;
for intracranial hemorrhage , gastric ulcer , nonspecific ulcerative colitis , lung tumors , tuberculosis and hyperfibrinolysis ;
children under 18 years of age;
if you are allergic to the components of the medicine;
galactose intolerance .

Caution should be exercised when combining the drug with acetylsalicylic acid , NSAIDs , heparin , thrombolytics , with renal and liver failure, before surgery.

Lopirel

- hypersensitivity to clopidogrel or any excipient of the drug; - severe liver failure; - acute bleeding (including bleeding from a peptic ulcer or intracranial hemorrhage); - pregnancy and lactation; - children under 18 years of age (efficacy and safety of use have not been established); - rare hereditary lactose intolerance, lactase deficiency and glucose-galactose malabsorption syndrome. With caution: - with moderate liver failure, in which there is a possible predisposition to bleeding (limited clinical experience); - for renal failure (limited clinical experience); - in case of injuries, surgical interventions (risk of increased bleeding); - for diseases in which there is a predisposition to the development of bleeding (especially gastrointestinal or intraocular); - with simultaneous administration of selective serotonin reuptake inhibitors (SSRIs); - while taking NSAIDs, incl. and selective COX-2 inhibitors; - with simultaneous administration of warfarin, heparin, glycoprotein IIb/IIIa inhibitors; - if there is a history of allergic and hematological reactions to other thienopyridines (such as ticlopidine, prasugrel) due to the possibility of cross-allergic and hematological reactions; - in patients with a genetically determined decrease in the function of the CYP2C19 isoenzyme (in patients who are weak CYP2C19 metabolizers, when clopidogrel is used in recommended doses, less active metabolite of clopidogrel is formed and its antiplatelet effect is less pronounced; - weak metabolizers receiving clopidogrel in recommended doses, in acute coronary syndrome or percutaneous coronary intervention may have a higher incidence of cardiovascular complications than patients with normal CYP2C19 function). Use during pregnancy and breastfeeding As a precautionary measure, the use of the drug Lopirel during pregnancy is contraindicated due to the lack of clinical data on its use by pregnant women, although animal studies of clopidogrel have not revealed any direct or indirect adverse effects on pregnancy, embryonic development, and childbirth and postnatal development. Breastfeeding should be discontinued when treated with Lopirel, because Studies in rats have shown that clopidogrel and/or its metabolites are excreted in breast milk. It is not known whether clopidogrel passes into human breast milk.

Side effects

Adverse reactions, ranked in order of decreasing likelihood of occurrence:

nosebleeds , hematomas , indigestion , bleeding in the gastrointestinal tract , diarrhea , subcutaneous hemorrhages ;
eosinophilia , headache , thrombocytopenia , paresthesia , loss of consciousness, flatulence , leukopenia , gastritis , nausea, constipation gastrointestinal ulcers ;
conjunctival, ocular, intracranial and retinal hemorrhages, decreased number of neutrophils and platelets in the blood;
neutropenia , retroperitoneal bleeding ;
TTP , agranulocytosis , taste distortion, anaphylactoid reactions , thrombocytopenia , aplastic anemia , hallucinations and confusion , vasculitis , low blood pressure ;
bronchospasm , colitis , hemoptysis, bullous dermatitis , pancreatitis , stomatitis , hepatitis , liver failure, Quincke's edema , myalgia , urticaria , arthralgia , lichen planus , eczema , arthritis , fever .

Lopirel, instructions for use (method and dosage)

The tablets are taken orally, regardless of food intake.

Instructions for use Lopirel (75 mg)

As a rule, for myocardial infarction, ischemic stroke , patients with diseases of the arteries in the periphery are prescribed 1 tablet once a day.

Duration of use after a heart attack is from 1 to 25 days, after a stroke – 7 days or 6 months.

If the patient has coronary syndrome ST elevation or has undergone coronary stenting , then treatment begins with a dose of 300 mg, and then is prescribed 75 mg (one tablet) 1 time per day for 3 months (the course can be extended to one year ). cetylsalicylic acid is additionally prescribed , the recommended dosage is 100 mg.

Lopirel

Suction

After a single dose and during a course of oral administration at a dose of 75 mg/day, clopidogrel is rapidly absorbed. The average maximum plasma concentration (Cmax) of unchanged clopidogrel is about 2.2-2.5 ng/ml and is reached approximately 45 minutes after administration. According to the excretion of clopidogrel metabolites by the kidneys, its absorption is at least 50%.

Distribution

In vitro

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 carboxylic acid derivative (85%) of

metabolites circulating in the systemic circulation, and the second way is through the cytochrome P450 system. Initially, clopidogrel is metabolized to 2-oxoclopidogrel, which is an intermediate metabolite. Subsequent metabolism of oxoclopidogrel leads to the formation of the active metabolite of clopidogrel, the thiol derivative of clopidogrel. In vitro

this metabolic pathway occurs with the participation of the isoenzymes CYP3A4, CYP2C19, CYP1A2 and CYP2B6.
in vitro
studies , rapidly and irreversibly binds to platelet receptors, thereby inhibiting platelet aggregation.

Removal

Pharmacogenetics

With the help of the CYP2C19 isoenzyme, both the active metabolite and the intermediate metabolite, 2-oxoclopidogrel, are formed. The pharmacokinetics and antiplatelet effect of the active metabolite of clopidogrel, when studying ex vivo platelet aggregation, vary depending on the genotype of the CYP2C19 isoenzyme.

In a crossover study conducted on 40 volunteers, 10 people in each group with four subtypes of the CYP2C19 isoenzyme (ultrarapid metabolizers, extensive metabolizers, intermediate metabolizers, poor metabolizers), the pharmacokinetics and antiplatelet effect of clopidogrel at a dose of 300 mg followed by its administration were assessed. 75 mg/day and when taking clopidogrel at a dose of 600 mg followed by 150 mg/day for 5 days (reaching an equilibrium state). There were no significant differences in active metabolite exposure and mean platelet aggregation inhibition (API) (ADP-induced) values between ultrarapid, extensive, and intermediate metabolizers. In poor metabolizers, exposure to the active metabolite was reduced by 63-71% compared to extensive metabolizers. When using the 300 mg/75 mg treatment regimen in poor metabolizers, the antiplatelet effect was reduced with average IAT values of 24% (at 24 hours) and 37% (at 5 days of treatment) compared with IAT of 39% (at 24 hours). and 58% (on day 5 of treatment) in extensive metabolizers and 37% (after 24 hours) and 60% (on day 5 of treatment) in intermediate metabolizers. When poor metabolizers received the 600 mg/150 mg regimen, exposure to the active metabolite was higher than when receiving the 300 mg/75 mg regimen. In addition, the IAT was 32% (at 24 hours) and 61% (at day 5 of treatment), which was greater than that of poor metabolizers receiving the 300 mg/75 mg regimen and was similar to that in groups of patients with higher CYP2C intensity 19-metabolism, receiving a treatment regimen of 300 mg/75 mg. However, clinical outcome studies have not yet established a clopidogrel dosing regimen for patients in this group.

The effect of CYP2C19 genotype on clinical outcomes in patients treated with clopidogrel has not been assessed in prospective, randomized, controlled studies. However, few retrospective analyzes are currently available. Genotyping results are available from the following clinical studies: CURE (n=2721), CHARISMA (n=2428), CLARITY-TIMI 28 (n=227), TRITON-TIMI 38 (n=1477) and ACTIVE-A (n=601) , as well as in several published cohort studies.

In the CHARISMA study and one cohort study (Simon), an increase in the incidence of cardiovascular events was observed only in poor metabolizers (when compared with extensive metabolizers).

In the CURE, CLARITY, ACTIVE-A and one of the cohort studies (Trenk), there was no increase in the incidence of cardiovascular events depending on the intensity of CYP2C19 metabolism.

Clinical studies to date have not had a sufficient sample size to detect differences in clinical outcome in patients with low CYP2C19 activity.

Pharmacokinetics in special clinical situations

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

In elderly volunteers (over 75 years old)

When compared with young volunteers, no differences were found in platelet aggregation and bleeding time. No dose adjustment is required in elderly patients.

Pharmacokinetics of clopidogrel in children

not studied.

In patients with severe kidney damage

(creatinine clearance (CC) 5-15 ml/min) after repeated doses of clopidogrel 75 mg/day, the initiation of ADP-induced platelet aggregation was lower (25%) compared with that in healthy volunteers, but the prolongation of bleeding time was similar to that in healthy volunteers receiving clopidogrel at a dose of 75 mg/day. Clopidogrel was well tolerated in all patients.

In patients with severe liver damage

After daily administration of clopidogrel 75 mg/day for 10 days, the inhibition of ADP-induced platelet aggregation was similar to that in healthy volunteers. The mean bleeding time was also comparable in both groups.

Interaction

When combining the drug with oral anticoagulants , in particular warfarin , the likelihood and duration of bleeding may increase.

In persons with an increased risk of bleeding and taking Lopirel, it is not recommended to additionally take glycoprotein IIb/IIIa inhibitors .

It has been proven that the combination of clopidogrel and naproxen increases the risk of developing hidden gastrointestinal bleeding. However, in the case of other NSAIDs , such a pattern has not been proven. Therefore, caution should be exercised when combining these drugs.

Despite the good results of clinical studies of the interaction of the drug with heparin , caution should be exercised when taking them simultaneously.

Combining the drug with thrombolytics , since the safety of such a combination has not been clearly established.

It has been proven that daily intake of acetylsalicylic acid (up to 1000 mg per day) and clopidogrel does not affect the aggregative properties of the drug. However, the duration of co-administration of these drugs should not exceed 1 year (caution should be exercised).

The medicine can be combined with atenolol , phenobarbital , estrogens , cimetidine or nifedipine .

The drug inhibits the metabolism of drugs pharmacokinetic parameters depend on the CYP2C9 isoenzyme . In particular, the medicine may increase plasma concentrations of phenytoin and tolbutamide . You need to be careful.

It is possible to combine the drug with digoxin, theophylline, and antacids .

Lopirel tablet p/o 75 mg in blister pack No. 10x9

Name

Lopirel tablet p/o 75 mg in blister pack No. 10x9

Description

A round, biconvex, pink film-coated tablet with an I symbol on one side.

Main active ingredient

Clopidogrel

Release form

7 or 10 tablets in an aluminum/aluminum blister. Blister No. 7 - 2 pieces, blister No. 10 - 3 or 9 in a cardboard box with instructions for use.

Dosage

75 mg

special instructions

A blood test should be performed during the first week of treatment when clopidogrel is combined with acetylsalicylic acid, NSAIDs, heparin, glycoprotein IIb/IIIa inhibitors or fibrinolytics, as well as in patients with an increased risk of bleeding (trauma, surgery or other pathological conditions). Due to the risk of bleeding and hematological side effects, if clinical symptoms indicating this appear during treatment, it is necessary to immediately conduct a blood test (aPTT, platelet count, platelet function tests) and liver function tests. In the case of surgical interventions, if the antiplatelet effect is undesirable, clopidogrel should be discontinued 7 days before surgery. Clopidogrel should be used with caution in patients at risk of bleeding (especially gastrointestinal and intraocular). Patients should be warned that they should report each case of bleeding to the doctor. Due to insufficient data, clopidogrel should not be prescribed in the acute period of ischemic stroke (in the first 7 days).

Pharmacodynamics

Clopidogrel is a prodrug and must be metabolized by CYP45C enzymes to form its active metabolite. The active metabolite of clopidogrel selectively blocks platelet P2Y12 receptors, inhibiting the binding of adenosine diphosphate (ADP) to these receptors and the subsequent ADP-mediated activation of the GPIIb/IIIa glycoprotein complex, thereby preventing platelet aggregation. The irreversibility of blockade of P2Y12 receptors persists for the entire remaining life of platelets (approximately 7-10 days), and restoration of normal platelet function occurs at a rate corresponding to the platelet cycle. Platelet aggregation induced by agonists other than ADP is also inhibited by blocking the increased platelet activation induced by released ADP. Because the active metabolite is formed by CYP450 enzymes, some of which are polymorphic or inhibited by other drug compounds, platelet suppression is not sufficient in all patients. Regular subsequent administration of the drug at a daily dose of 75 mg leads to significant inhibition of platelet aggregation caused by ADP. The inhibitory effect increases progressively and an equilibrium state is achieved after 3-7 days. At the same time, the average level of inhibition under the influence of a daily dose of 75 mg was from 40 to 60%. Platelet aggregation and bleeding time gradually returned to baseline levels an average of 5 days after cessation of treatment.

Pharmacokinetics

Absorption After single and repeated oral doses of 75 mg per day, clopidogrel is rapidly absorbed. Mean maximum plasma concentrations of unmetabolized clopidogrel (approximately 2.2 to 2.5 ng/mL after a single 75 mg oral dose) occurred approximately 45 minutes after dosing. Based on clopidogrel metabolites excreted in the urine, absorption is at least 50%. Distribution Clopidogrel and its main (inactive) circulating metabolite are reversibly bound to human plasma proteins in vitro (98 and 94%, respectively). This bond remains unsaturated in vitro over a wide range of concentrations. Metabolism Clopidogrel undergoes extensive metabolism in the liver. In vitro and in vivo, clopidogrel is metabolized in two main ways: one is mediated by esterases and leads to hydrolysis to an inactive carboxylic acid derivative (85% of metabolites in the bloodstream), the other (15% of metabolites) is mediated by numerous cytochrome P450s. Clopidogrel is first metabolized to an intermediate metabolite, 2-oxo-clopidogrel. Subsequent metabolism of 2-oxo-clopidogrel leads to the formation of an active metabolite, the thiol derivative of clopidogrel. In vitro, this metabolic pathway is mediated by CYP3A4, CYP2C19, CYP1A2 and CYP2B6. The active thiol metabolite, which has been isolated in vitro, rapidly and irreversibly binds to platelet receptors, thereby inhibiting platelet aggregation. Elimination Following an oral dose of a radioactive drug (14C-labeled clopidogrel), approximately 50% of the drug is excreted in the urine and approximately 46% in the feces within 120 hours of administration. After one 75 mg oral dose, the half-life of clopidogrel is 6 hours. The half-life of the main circulating (inactive) metabolite is 8 hours after single and repeated doses.

Pharmacogenetics

CYP2C19 is involved in the formation of the active metabolite and intermediate metabolite, 2-oxo-clopidogrel. The pharmacokinetics and antiplatelet effects of the active metabolite of clopidogrel, as measured in an ex vivo platelet aggregation test, vary depending on the CYP2C19 genotype. The CYP2C19*1 allele corresponds to a fully functioning metabolism, whereas the CYP2C19*2 and CYP2C19*3 alleles correspond to reduced metabolism. The CYP2C19*2 and CYP2C19*3 alleles account for the majority of reduced function alleles in white (85%) and Asian (99%) poor metabolizers. Other reduced function alleles include CYP2C19*4, *5, *6, *7, and *8, among others. Patients with reduced metabolic function are carriers of two nonfunctional alleles. According to published data, the frequency of occurrence of the genotype with low metabolic activity of cytochrome CYP2C19 is approximately 2% in whites, 4% in blacks and 14% in Asians. Special Populations The pharmacokinetics of the active metabolite in the following special populations is unknown. Renal Impairment Following repeated doses of clopidogrel 75 mg daily in subjects with severe renal disease (creatinine clearance 5 to 15 mL/min), the suppression of ADP-induced platelet aggregation was weaker (25%) than that observed in healthy subjects, however , the prolongation of bleeding time was similar to that observed in healthy subjects receiving 75 mg of clopidogrel per day. In addition, clinical tolerability was good in all patients. Hepatic Impairment Following repeated doses of clopidogrel 75 mg daily for 10 days in patients with severe hepatic impairment, the suppression of ADP-induced platelet aggregation was similar to that observed in healthy subjects. The mean prolongation of bleeding time was similar in both groups. Race The prevalence of CYP2C19 alleles that result in intermediate and poor metabolism by CYP2C19 varies by race or ethnicity (see Pharmacogenetics section). There is limited data in the literature in Asian populations to evaluate the clinical impact of this CYP genotype on clinical outcomes of adverse reactions.

Indications for use

Clopidogrel is indicated for the prevention of atherothrombotic disorders in:

Patients who have had a myocardial infarction (several days to less than 35 days), ischemic stroke (7 days to less than 6 months), or diagnosed peripheral arterial disease.
Patients suffering from acute coronary syndrome:

acute coronary syndrome without ST segment elevation (unstable angina or non-Q wave myocardial infarction), including patients subject to percutaneous coronary intervention, in combination with acetylsalicylic acid (ASA). acute myocardial infarction with ST segment elevation, in combination with acetylsalicylic acid in patients receiving drug treatment, in whom thrombolytic therapy may be considered. Clopidogrel is indicated for use in adult patients to prevent atherothrombotic and thromboembolic complications in atrial fibrillation. In patients with atrial fibrillation (AF) at increased risk of cardiovascular complications, who are unable to receive vitamin K antagonist (VKA) therapy, and who have a low risk of bleeding, clopidogrel is indicated for use in combination with ASA to prevent atherothrombotic and thromboembolic complications. including stroke.

Directions for use and doses

Adults and elderly patients: The usual daily dose of clopidogrel is 75 mg once daily, regardless of meals. In patients suffering from acute coronary syndrome: Non-ST segment elevation acute coronary syndrome (unstable angina or non-Q wave myocardial infarction): treatment with clopidogrel should be started with a single loading dose of 300 mg and then continued with a dose of 75 mg once daily (with acetylsalicylic acid). acid at a dose of 75 - 325 mg per day). Since higher doses of acetylsalicylic acid are associated with an increased risk of bleeding, it is not recommended to exceed a dose of acetylsalicylic acid of 100 mg. The optimal duration of treatment has not been formally established. Data from clinical studies support the use of the regimen for up to 12 months, with maximum benefit observed after 3 months. Acute ST-segment elevation myocardial infarction: clopidogrel can be used as a single daily dose of 75 mg, with initiation of treatment at a loading dose of 300 mg in combination with acetylsalicylic acid with or without other thrombolytics. In patients over 75 years of age, treatment with clopidogrel should be started without a loading dose. Combination therapy is started as soon as possible after the onset of symptoms and continued for at least four weeks. The benefit of combining clopidogrel with acetylsalicylic acid after four weeks has not been studied in this context. Atrial fibrillation: Clopidogrel should be prescribed as a single daily dose of 75 mg. Prescribe ASA (75-100 mg/day) and continue taking it in combination with clopidogrel. If a dose is missed:

Less than 12 hours after the usual dosing time: Patients should take the dose immediately and the next dose should be taken at the scheduled time.
More than 12 hours after the usual dosing time: The patient should take the next dose at the scheduled time, without doubling it.

Children and adolescents: The drug is not used in this group of patients (see Contraindications), since the effectiveness and safety of clopidogrel in children and adolescents has not been studied. Renal impairment: Therapeutic experience with the use of clopidogrel in patients with impaired renal function is limited. Therefore, the drug should be prescribed to such patients with caution. Liver dysfunction: Clopidogrel should be prescribed with caution to patients with moderate liver dysfunction who may experience bleeding diathesis, since experience with the drug in such patients is limited.

Use during pregnancy and lactation

Due to lack of data, it is not recommended.

Precautionary measures

Bleeding and hematological side effects If clinical symptoms indicating a risk of bleeding and hematological side effects appear during treatment, a blood test should be performed immediately. Like other antiplatelet drugs, clopidogrel should be used with caution in patients at increased risk of bleeding associated with trauma, surgery or other pathological conditions, as well as when clopidogrel is combined with acetylsalicylic acid, non-steroidal anti-inflammatory drugs, including COX-inhibitors. 2, heparin, or glycoprotein IIb/IIIa inhibitors. Patients should be closely monitored for signs of bleeding, including occult bleeding, especially during the first weeks of treatment and/or after invasive cardiac procedures or surgery. The combined use of clopidogrel with oral coagulants is not recommended, since this combination may increase the intensity of bleeding. In the case of surgical interventions, if the antiplatelet effect is undesirable, the course of treatment with clopidogrel should be discontinued 5-7 days before surgery. Patients should also inform their doctor and dentist about taking the drug if they are undergoing surgery or if the doctor prescribes a new drug for the patient. Clopidogrel prolongs bleeding time and should be used with caution in patients at risk of bleeding (especially gastrointestinal and intraocular). Patients should be warned that since stopping bleeding that occurs during the use of clopidogrel (alone or in combination with acetylsalicylic acid) requires more time, they should inform the doctor about each case of unusual (in terms of location and/or duration) bleeding. Thrombotic thrombocytopenic purpura (TTP) Very rarely, cases of thrombotic thrombocytopenic purpura (TTP) have been reported following the use of clopidogrel, sometimes for short periods of time. They are characterized by thrombocytopenia and microangiopathic hemolytic anemia associated with neurological impairment, renal dysfunction or hyperthermia. TTP is a life-threatening condition that requires immediate intervention, including plasmapheresis. The drug contains lactose, so it should not be taken by patients with rare hereditary disorders of galactose tolerance, Lapp lactase deficiency or glucose-galactose malabsorption syndrome. The simultaneous administration of clopidogrel with proton pump blockers, for which there is evidence of their ability to weaken the therapeutic effectiveness of clopidogrel, should be avoided. Omeprazole/esomeprazole is one such medicine. If a patient needs to take proton pump blockers while taking clopidogrel, those drugs in this group that have the least pronounced ability to interact should be prescribed. Pantoprazole is one such medicine. Cross-reactivity among thienopyridines Patients should be assessed for a history of hypersensitivity to thienopyridines (eg, clopidogrel, ticlopidine, prasugrel) as cross-reactivity among thienopyridines has been reported. Thienopyridines may cause mild to severe allergic reactions such as rash, angioedema or hematological cross-reactions such as thrombocytopenia and neutropenia. Patients with a history of allergic reactions and/or hematological reactions to one of the thienopyridines may be at increased risk of developing the same or a different reaction to another thienopyridine. Monitoring for signs of hypersensitivity in patients with a known allergy to thienopyridines is recommended.

Interaction with other drugs

Oral anticoagulants: Concomitant use of clopidogrel with warfarin is not recommended, as this combination may increase bleeding. Glycoprotein IIb/IIIa inhibitors: Prescribing glycoprotein IIb/IIIa inhibitors with clopidogrel requires caution. Acetylsalicylic acid: Acetylsalicylic acid does not change the inhibitory effect of clopidogrel on ADP-induced platelet aggregation, but clopidogrel enhances the effect of acetylsalicylic acid on collagen-induced platelet aggregation. The combined use of these drugs requires caution. However, in patients suffering from acute coronary syndrome without ST segment elevation, long-term combined use of clopidogrel and acetylsalicylic acid (up to 1 year) is recommended. Heparin: In a clinical trial conducted in healthy subjects, clopidogrel did not alter either the requirement for heparin or the effect of heparin on blood clotting. Concomitant use of heparin did not change the inhibitory effect of clopidogrel on platelet aggregation. However, the safety of this combination has not yet been established, and the simultaneous use of these drugs requires caution. Thrombolytics: The safety of concomitant use of clopidogrel, recombinant tissue plasminogen activator (rt-PA) and heparin has been studied in patients with recent myocardial infarction. The incidence of clinically significant bleeding was similar to that observed with concomitant use of rt-PA and heparin. The safety of combined use of clopidogrel with other thrombolytics has not yet been established and the simultaneous use of these drugs requires caution. NSAIDs: Prescribing NSAIDs together with clopidogrel requires caution (increased risk of bleeding). Combined use with other drugs: no clinically significant pharmacodynamic interaction was found when clopidogrel was used in combination with atenolol, nifedipine, phenobarbital, cimetidine, estrogens, digoxin, theophylline, phenytoin, tolbutamide and antacids. Proton pump inhibitors: The combined use of drugs containing clopidogrel and omeprazole/esomeprazole is unacceptable. Concomitant use of clopidogrel with pantoprazole is allowed. With the exception of the specific information on drug incompatibility given above, no studies have been conducted on the interaction of clopidogrel and some drugs commonly used in patients with atherothrombosis. However, patients participating in clinical trials of clopidogrel were concomitantly treated with a variety of drugs, including diuretics, beta-blockers, ACE inhibitors, calcium channel antagonists, cholesterol-lowering drugs, coronary vasodilators, antidiabetic drugs (including insulin), antiepileptic drugs, hormone replacement therapy and GPIIb/IIIa antagonists, with no evidence of clinically significant adverse interactions.

Contraindications

Hypersensitivity to the active and/or auxiliary components of the tablet (including soy and peanuts), severe liver failure, acute bleeding, such as with peptic ulcers or intracranial hemorrhage, pregnancy, breastfeeding, children under 18 years of age (safety and effectiveness applications not established). With caution - in case of liver and kidney diseases (moderate liver and/or renal failure), injuries, preoperative conditions.

Compound

One film-coated tablet contains the active substance - clopidogrel 75 mg in the form of clopidogrel bisulfate 97.87 mg. Excipients: lactose anhydrous, microcrystalline cellulose, crospovidone (type A), glycerol dibehenate, talc and Opadry II Pink shell composition: polyvinyl alcohol, talc, titanium oxide (E171), macrogol 3350, lecithin (E322), red iron oxide (E172 ).

Overdose

An overdose of clopidogrel can lead to prolongation of bleeding time and subsequent complications. If bleeding is detected, appropriate treatment should be applied. Antidote unknown. If rapid correction of prolonged bleeding time is necessary, the effect of clopidogrel can be stopped by platelet transfusion.

Side effect

Clinically significant side effects noted in a number of large international studies, with a frequency of ? 0.1%, as well as all severe side effects, are presented below, according to the WHO classification. Hemostasis: in patients receiving clopidogrel, gastrointestinal bleeding occurred in 2.0% of cases, and in 0.7% of cases required hospitalization. Less common were hematomas, hematuria and conjunctival hemorrhages, and prolongation of bleeding was uncommon. Reports of bleeding were the most common. Most cases occurred during the first month of treatment. Central and peripheral nervous system: often - headache, dizziness, paresthesia; rarely - vertigo. Gastrointestinal tract: often - dyspepsia (diarrhea), abdominal pain; infrequently - nausea, gastritis, flatulence, constipation, vomiting, peptic ulcer of the stomach and duodenum, very rarely - colitis (including ulcerative or lymphocytic colitis), pancreatitis, stomatitis. Hematopoiesis: infrequently - leukopenia, decreased number of neutrophils and eosinophilia, decreased platelet count, very rarely - thrombocytopenic thrombotic purpura (in 0.0005%, i.e. 1/200,000 patients), severe thrombocytopenia (platelet count ? 30 * 109/l ), granulocytopenia, agranulocytosis, anemia and aplastic anemia/pancytopenia. Dermatological reactions: uncommon - rash and itching. Disorders of the liver and biliary tract: cases of deviation from normal values of liver tests have rarely been observed, very rarely - hepatitis, acute liver failure. Immune system: angioedema, anaphylactic reactions, and serum sickness have been observed extremely rarely. Mental disorders: very rarely - confusion, hallucinations. Sense organs: very rarely - changes in taste sensations. Vascular system: very rarely - vasculitis, decreased blood pressure. Respiratory system: extremely rarely - bronchospasm, interstitial pneumonitis. Dermatological reactions: very rarely - angioedema, bullous rash (multiform, erythema), erythematous rash, urticaria, eczema, lichen planus. Musculoskeletal system: very rarely - arthralgia, arthritis. Kidneys and urinary system: very rarely - glomerulonephritis. General condition: very rarely - elevated body temperature. Laboratory tests: very rarely - abnormal results of liver function tests, increased blood creatinine levels.

Storage conditions

At a temperature not exceeding 30 °C. Keep out of reach of children. 36 months. Do not use after expiration date.

special instructions

For persons who have suffered an acute myocardial infarction with ST elevation, therapy with the drug should be postponed for 2-3 days.

If bleeding occurs during treatment with the drug, blood tests and liver enzyme .

Particular caution should be observed when combining the drug with NSAIDs , aspirin, heparin, thrombolytics , during operations, injuries, and an increased risk of bleeding.

The drug is not prescribed to persons who have suffered an acute ischemic stroke if less than a week has passed.

If you are having surgery, an appointment with a dentist or other doctor, you must inform the specialist that you are taking this drug. You should stop taking Lopirel at least a week before the intended surgery.

You must report to your doctor any cases of bleeding that occur during treatment with the drug. Please be aware that it may take longer than usual to stop.

Instructions for use LOPIREL

Bleeding and hematological side effects

If hematological side effects or clinical symptoms indicating a risk of bleeding occur during treatment, it is necessary to immediately conduct a blood test (aPTT, platelet count, platelet functional activity indicators) and an assessment of the functional activity of the liver.

Like other antiplatelet drugs, clopidogrel should be used with caution in patients at increased risk of bleeding associated with trauma, surgery or other pathological conditions, as well as in the case of a combination of clopidogrel with acetylsalicylic acid, NSAIDs (including COX-inhibitors). 2), heparin, or glycoprotein IIb/IIIa inhibitors. Patients should be closely monitored for signs of bleeding, including occult bleeding, especially during the first weeks of treatment and/or after invasive cardiac procedures or surgery. The combined use of clopidogrel with oral coagulants is not recommended, since this combination may increase the intensity of bleeding.

During surgical interventions, if the antiplatelet effect is undesirable, the use of clopidogrel should be discontinued 5-7 days before surgery. Patients should inform their doctor (including dentist) about the use of the drug before upcoming surgical interventions, or if the doctor prescribes a new drug for the patient.

Clopidogrel prolongs bleeding time and should therefore be used with caution in patients at risk of bleeding (especially gastrointestinal and intraocular).

Patients should be warned that stopping bleeding that occurs during the use of clopidogrel (alone or in combination with acetylsalicylic acid) requires more time, so they should inform the doctor about each case of unusual (in terms of location and/or duration) bleeding.

Due to insufficient data, clopidogrel should not be prescribed in the acute period of ischemic stroke (in the first 7 days).

Thrombotic thrombocytopenic purpura (TTP)

Very rarely, cases of TTP characterized by thrombocytopenia and microangiopathic hemolytic anemia associated with neurological disorders, renal dysfunction or hyperthermia have been reported after the use of clopidogrel, sometimes for short periods. TTP is a life-threatening condition that requires immediate intervention, including plasmapheresis.

Lactose

The drug contains lactose, so it should not be prescribed to patients with rare hereditary disorders of galactose tolerance, lapp lactase deficiency or glucose-galactose malabsorption syndrome.

Proton pump inhibitors

Clopidogrel should not be co-administered with proton pump inhibitors, for which there is evidence that they may reduce the therapeutic efficacy of clopidogrel (omeprazole/esomeprazole). If a patient needs to take proton pump inhibitors simultaneously with clopidogrel, then only those drugs of this group that have a less pronounced potential for interaction (for example, pantoprazole) should be prescribed.

Impact on the ability to drive vehicles and operate machinery

The drug does not affect or has an insignificant effect on the ability to drive vehicles and operate machinery.

Lopirel's analogs

Level 4 ATC code matches:
Persantine

Aegitromb

Plavix

Coplavix

Chime

Cardiomagnyl

Polocard

Thrombo ACC

Brilinta

Magnicor

Plagril

Dipyridamole

Clopidogrel

Sylt

CardiASK

Aspirin Cardio

Acecardole

Aspinat

Aspicor

Analogues of the drug: Clopidogrel, Avix, Atrogrel, Deplat, Zilt, Karum-Sanovel, Clopidal, Clopicor, Lopigrol, Orogrel, Plavigrel, Plagril, Reodar, Tessiron, Trombonet, Flamogrel 75, Atherocard, Gridoklein, Deplatt, Cardogrel, Clodia, Clorelo, Medogrel, Pingel Neo, Plavix, Platogril, Reomax, Trombex .

Lopirel price

The price of Lopirel 75 mg (28 tablets) is approximately 460 rubles.

Online pharmacies in RussiaRussia
Online pharmacies in UkraineUkraine
Online pharmacies in KazakhstanKazakhstan

LuxPharma* special offer

Lopirel tablet
75 mg N90 RUB 1,480 order

ZdravCity

Lopirel tablets p.p.o. 75 mg 100 pcs. Actavis LTD
RUB 1,284 order
Lopirel tablets p.p.o. 75 mg 28 pcs Actavis LTD
685 rub. order

Pharmacy Dialogue

Lopirel (tab.p.pl/vol. 75 mg No. 100) Actavis
RUB 1,171 order
Lopirel (tab.p.pl/vol. 75 mg No. 28) Actavis
RUR 674 order

Pharmacy24

Lopirel 75 mg N30 Actavis Ltd, Malta/Erow Pharm (Malta) Ltd, Malta
71 UAH order

PaniPharmacy

Lopirel tablets Lopirel tablets 75 mg No. 30 Malta, Actavis
81 UAH order
Lopirel tablets Lopirel tablets 75 mg No. 90 Malta, Actavis
402 UAH order