CLOPIVEN-LM [Clopidogrel] 75 mg Film-coated tablets
CLOPIVEN-LM
instructions for the medical use of the medicinal
product
Tradename
Clopiven-LM, Клопивен-LM
International
non-proprietary name or generic name
Clopidogrel, Клопидогрел
Composition
Each film-coated tablet contains:
Active substance: clopidogrel (as clopidogrel
bisulfate) 75 mg.
Excipients: lactose monohydrate, avicel 200, aerosil 200,
povidone, primogel, magnesium stearate, PVP K-30.
Tablets.
Antiplatelet agent.
Pharmacodynamics
Clopidogrel is a prodrug, one of the
active metabolites of which is an inhibitor of platelet aggregation. For the
formation of an active metabolite that inhibits platelet aggregation,
clopidogrel must be metabolized using isoenzymes of the cytochrome P450 (CYP450)
system. The active metabolite of clopidogrel selectively inhibits the binding
of ADP to the P2Y12 platelet receptor and subsequent ADP-mediated activation of
the GPIIb / IIIa complex, leading to suppression of platelet aggregation. Due
to irreversible binding, platelets remain immune to ADP stimulation for the
rest of their life (approximately 7-10 days), and the restoration of normal
platelet function occurs at a rate corresponding to the rate of platelet
renewal.
After a single dose and with a course of oral
administration at a dose of 75 mg per day, clopidogrel is rapidly absorbed.
Absorption and bioavailability are high. However, the concentration of the
starting substance in the blood plasma is insignificant and does not reach the
measurement limit (0.25 μg / L) 2 hours after ingestion. Clopidogrel and the
main metabolite bind reversibly to blood plasma proteins (98% and 94%,
respectively).
Clopidogrel is rapidly biotransformed in the liver.
Clopidogrel is a prodrug. The active metabolite, a thiol derivative, is not
detected in plasma. The main metabolite to be determined, a derivative of
carboxylic acid, is inactive, accounting for about 85% of the compound
circulating in the plasma. The maximum concentration (Cmax) of this metabolite
in the blood plasma after repeated doses of clopidogrel at a dose of 75 mg is
about 3 mg / l and is reached approximately 1 hour after administration.
About 50% of the dose taken is excreted by the kidneys
and approximately 46% is excreted by the intestines within 120 hours after
administration. The half-life (T1 / 2) of the main metabolite after single and
repeated doses is 8 hours.
Prevention of thrombotic complications:
- after a myocardial infarction (from several days to
35 days), ischemic stroke (from 7 days to 6 months) or with diagnosed
peripheral arterial disease;
- in acute coronary syndrome without ST-segment
elevation (unstable angina / myocardial infarction without Q wave), including
patients who should receive medical treatment, and patients who are indicated
for percutaneous coronary intervention (with or without stenting) or coronary
artery bypass grafting (CABG) , in combination with acetylsalicylic acid;
- in acute coronary syndrome with ST segment elevation
(acute myocardial infarction) in combination with acetylsalicylic acid, in
patients receiving drug treatment with the possible use of thrombolytic
therapy.
Prevention of atherothrombotic and thromboembolic
complications in adult patients with atrial fibrillation (atrial fibrillation).
Contraindications
• severe liver failure;
• acute bleeding (for example, with a peptic ulcer or
intracranial hemorrhage);
• pregnancy;
• period of breastfeeding;
• age up to 18 years;
• hypersensitivity to the components of the drug.
Method of administration and dosage
Inside, without chewing, with a small amount of
liquid.
For the prevention of ischemic disorders in patients
after myocardial infarction, ischemic stroke and diagnosed peripheral arterial disease
- 75 mg 1 time / day. Treatment should be started within a period from several
days to 35 days after myocardial infarction and from 7 days to 6 months after
ischemic stroke.
In acute coronary syndrome without ST segment
elevation (unstable angina pectoris or myocardial infarction without Q wave),
treatment should begin with a single loading dose of 300 mg, and then continue
to use the drug at a dose of 75 mg 1 time / day (with the simultaneous
administration of acetylsalicylic acid in a dose 75-325 mg / day). Since the
use of acetylsalicylic acid in high doses is associated with a high risk of
bleeding, the recommended dose should not exceed 100 mg. The course of
treatment is up to 1 year.
In acute myocardial infarction with ST segment
elevation, the drug is prescribed at a dose of 75 mg 1 time / day using an
initial loading dose of 300 mg in combination with acetylsalicylic acid in
combination with or without thrombolytics. For patients over 75 years of age,
the drug should be administered without a loading dose. Combination therapy
should be started as early as possible after symptom onset and continued for at
least 4 weeks.
For patients with atrial fibrillation, take 75 mg 1
time / day in combination with acetylsalicylic acid (75-100 mg per day).
Special instructions and precautions
Clopven-LM should
be used with caution in patients at risk of severe bleeding during trauma,
surgery, in the acute period of ischemic stroke (in the first 7 days), in liver
and kidney diseases (including with moderate hepatic and / or renal failure );
patients receiving acetylsalicylic acid, NSAIDs (including COX-2 inhibitors),
heparin, or glycoprotein IIb / IIIa inhibitors. Careful monitoring of patients
is necessary to detect any signs of bleeding, including latent, especially
during the first weeks of using the drug and / or after invasive cardiac
procedures or surgery. In case of planned surgical interventions, the course of
treatment should be discontinued 7 days before the operation.
Patients should be
warned that the bleeding will take longer than usual to stop, so they should
inform the doctor about each case of bleeding.
Influence on the
ability to drive vehicles and mechanisms:
Due to the
possibility of dizziness while taking the drug, care should be taken when
driving vehicles and engaging in other potentially hazardous activities that
require increased concentration of attention and speed of psychomotor
reactions.
Application during pregnancy and during breastfeeding
Contraindicated during pregnancy and
lactation.
Interaction with other medicinal products
With the simultaneous use of clopidogrel and drugs,
the use of which is associated with the risk of bleeding (warfarin, IIb / IIIa
receptor blockers, acetylsalicylic acid, heparin, fibrin-specific or
fibrin-nonspecific thrombolytic agents, NSAIDs, selective serotonin reuptake
inhibitors), there is an increased the risk of bleeding due to their potential
additive effect with clopidogrel. Treatment should be done with caution.
Since clopidogrel is metabolized to the formation of
its active metabolite in part by the isoenzyme CYP2C19, the use of drugs that
inhibit this isoenzyme may lead to a decrease in the formation of the active
metabolite of clopidogrel. Avoid the simultaneous use of clopidogrel and potent
or moderate inhibitors of the isoenzyme CYP2C9 (omeprazole, esomeprazole,
fluvoxamine, fluoxetine, moclobemide, voriconazole, fluconazole, ticlopidine,
ciprofloxacin, cimetidine, carbamazepazine, oxscarbazepine).
Caution should be exercised with the simultaneous use
of clopidogrel and drugs metabolized by the CYP2C8 isoenzyme (eg, repaglinide,
paclitaxel) due to the risk of an increase in their plasma concentrations.
From the digestive
system: diarrhea, abdominal pain, dyspepsia, nausea, gastritis, bloating,
constipation, vomiting, stomach and duodenal ulcers, colitis (including
ulcerative colitis or lymphocytic colitis), pancreatitis, stomatitis.
From the liver and
biliary tract: hepatitis (non-infectious), acute liver failure.
From the
hematopoietic system: an increase in bleeding
time, a decrease in the number of platelets in the peripheral blood,
leukopenia, a decrease in the number of neutrophils in the peripheral blood,
eosinophilia, cases of serious bleeding, mainly subcutaneous, musculoskeletal,
ocular hemorrhages (conjunctival, in the tissue and retina of the eye),
bleeding from the respiratory tract (hemoptysis, pulmonary hemorrhage),
epistaxis, hematuria and bleeding from postoperative wounds and cases of fatal bleeding
(especially intracranial hemorrhage, gastrointestinal bleeding and
retroperitoneal hemorrhage), agranulocytosis, granulocytopenia, apocytopenia,
apcytopenia thrombotic thrombocytopenic purpura, acquired hemophilia A.
From the nervous
system: headache, paresthesia, dizziness, taste disturbances, ageusia.
From the side of the
psyche: confusion, hallucinations.
From the side of the
cardiovascular system: Kounis syndrome
(vasospastic allergic angina / allergic myocardial infarction), caused by a
hypersensitivity reaction to clopidogrel, vasculitis, decreased blood pressure.
From the respiratory
system: bronchospasm, interstitial pneumonia, eosinophilic pneumonia.
From the immune
system: anaphylactoid reactions, serum sickness, cross-allergic and
hematological reactions with other thienopyridines (such as ticlopidine,
prasugrel).
On the part of the
skin and subcutaneous tissues: skin rash, itching,
macular-papular erythematous or exfoliative rash, urticaria, pruritus,
angioedema, bullous dermatitis (erythema multiforme, Stevens-Johnson syndrome,
toxic epidermal necrolysis syndrome), acute epidermal necrolysis syndrome,
acute drug hypersensitivity, drug rash with eosinophilia and systemic
manifestations (DRESS syndrome), eczema, lichen planus.
From the
musculoskeletal system: arthralgia, arthritis,
myalgia, hemarthrosis.
From the urinary
system: hematuria, glomerulonephritis.
From the reproductive
system: gynecomastia.
On the part of
laboratory indicators: deviation from the norm of
laboratory indicators of the functional state of the liver, an increase in the
concentration of creatinine in the blood.
Others: fever.
If any of the side effects indicated in the instructions are
aggravated, or you notice any other side effects not listed in the
instructions, inform your doctor.
Symptoms: lengthening of bleeding time and subsequent
complications.
Treatment: if bleeding occurs, appropriate therapy should
be carried out. If rapid correction of prolonged bleeding time is required,
platelet transfusion is recommended. There is no specific antidote.
Store in a dry and
dark place at a temperature not exceeding 25°C.
Keep out of the reach
of children!
2 years. Do not use after the expiration date printed
on the package.
Dispensed by
prescription.
Release form
14 tablets in
aluminum foil blister. 2 blisters with instructions for use in a cardboard box.