Lopirel (clopidogrel) tablets

Release form and composition:

Tablets, film-coated pink, round, lenticular, with engraving I on one side.

1 tablet contains: clopidogrel hydrosulfate 97.87 mg,

emerce equivalent to the content of clopidogrel base 75 mg

Excipients: lactose, cellulose microcrystalline, crospovidone (type A), magnesium sulphate heptahydrate dibehenate, talc, Opadry II 85 G34669 pink (polyvinyl alcohol, talc, titanium dioxide (E171), macrogol 3350, lecithin (E322), colouring agent iron oxide red (E172)).

7 PCs. – blisters (4) – packs of cardboard.

Pharmacological action:

Antiplatelet drug, specific and active inhibitor of platelet aggregation. Having koronrodilatirtee action. Selectively reduces the binding of ADP receptors on platelets and activation of the receptors of the GPI Ib/IIIa by the action of ATP, reducing, thus, platelet aggregation. Reduces agregatia platelets, caused by other agonists, preventing activation of the released ADP, does not affect the activity of PDE. Irreversibly binds to ADP-receptors platelets, which remain impervious to the stimulation of ADP throughout the life cycle (about 7 days).

Inhibition of platelet aggregation observed after 2 h after administration (40% inhibition) initial dose of 400 mg. the Maximum effect (60% suppression of aggregation) develops after 4-7 days of admission in a dose of 50-100 mg/day. Antiplatelet effect lasts for the entire period of life of platelets (7-10 days).

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

Pharmacokinetics:

Suction

High absorption, high bioavailability, plasma concentration is low and 2 hours after admission does not reach the limit of measurement (0.025 µg/l).

Distribution

The plasma protein binding is 94-98%.

Metabolism

Metabolized in the liver. The main metabolite – inactive derivative carboxylato acid. After intake repeated doses of 75 mg Cmax of metabolite in plasma is about 3 mg/l and is achieved through 1 h.

Excretion

Display memory – 50%, through the intestines – 46% (during 120 h after injection). T1/2 the main metabolite after single and repeated administration is 8 h. the concentration of secreted metabolites by the kidneys – 50%.

Pharmacokinetics in special clinical cases

After taking the drug in a dose 75 mg/day concentration of the main metabolite in plasma are lower in patients with severe kidney disease (QC 5-15 ml/min) compared to patients with kidney disease of moderate severity (QC of 30 to 60 ml/min) and healthy subjects.

Indications:

Prevention of atherothrombosis:

— patients with myocardial infarction, ischemic stroke, or diagnosed peripheral arterial disease

— in patients with acute coronary syndrome without ST-segment elevation (unstable angina or myocardial infarction without the Q wave on the ECG), in combination with acetylsalicylic acid.

Dosing regimen:

The drug is administered orally at 75 mg 1 times/day regardless of the meal.

Treatment should begin within a few days to 35 days in patients after myocardial infarction and from 7 days to 6 months in patients after ischemic stroke.

Patients with acute coronary syndrome without ST-segment elevation (unstable angina or myocardial infarction without the Q wave on the ECG) treatment Laperla start with a single dose of 300 mg, and then continue to the dose 75 mg 1 times/day (with acetylsalicylic acid at a dose 75-325 mg/day). The optimal duration of treatment not established. Is effective treatment duration up to 12 months, the maximum effect is noted after 3 months after the start of treatment.

Side effects:

Determination of the frequency of adverse reactions: often (gt1/100 t1/10), sometimes (gt1/1000, t1/100), rare (gt1/10 000, t1/1000), very rare (t1/10 000).

CNS: sometimes – headache, dizziness, paraesthesia very rare – confusion, hallucinations, impaired taste sensation.

From the digestive system: often – neuralgia, pain in the abdomen, diarrhea and sometimes – nausea, gastritis, flatulence, constipation, vomiting, gastric ulcer and duodenal ulcer very rarely – colitis (including ulcerative or lymphocytic), pancreatitis.

From the hepato-biliary system: very rarely – hepatitis, increase in liver transaminases.

On the part of the blood: sometimes – leukopenia, reduction in the number of neutrophilic and eosinophilic granulocytes, decreased platelet count rarely – severe thrombocytopenia (platelet count e30-109/l), granulocytopenia, agranulocytosis, anaemia and aplastic anaemia/pancytopenia.

Side coagulation: sometimes – prolonged bleeding time very rare: thrombocytic thrombocytopenic purpura (1 case per 200 000 patients) often – bleeding of different localization and intensity. Most cases of bleeding were observed during the 1st month of treatment (especially intracranial, gastrointestinal and retroperitoneal bleeding) severe cases, skin bleeding (purpura), bleeding into joints and soft tissues (haemarthrosis, haematoma), eye bleeding (conjunctival, ocular, retinal), nasal bleeding, respiratory tract (hemoptysis, pulmonary hemorrhage), hematuria, and bleeding from the surgical wound.

Dermatological reactions: sometimes – rashes and itching very rarely – bullous rash (erythema multiforme), erythematous rash, oral lichen planus.

Allergic reactions: very rarely – urticaria, anaphylactoid reactions.

From the side of cardiovascular system: very rarely – vasculitis, hypotension.

The respiratory system: very rarely – bronchospasm.

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

From the urinary system: very rarely – glomerulonephritis, increased creatinine in the serum.

Other: very rarely – fever.

Contraindications:

— severe hepatic insufficiency

— hemorrhagic syndrome

— acute bleeding (including intracranial hemorrhage) and disease, predisposing to the development (ulcers disease stomach and duodenal ulcers in the phase of deterioration, ulcerative colitis, tuberculosis, lung tumor, hyperfibrinolysis)

— pregnancy

— lactation (breast feeding)

— the neonatal period

— the age 18 years (effectiveness and safety have not been established)

— intolerance of galactose, lactase deficiency or malabsorption of glucose-galactose (as in the preparation includes lactose)

— hypersensitivity to the drug.

With caution should use the drug in patients with moderate hepatic and/or renal failure, injuries, in the preoperative period at the same time with acetylsalicylic acid, NSAIDs (including COX-2 inhibitors), warfarin, thrombolytic agents, heparin, inhibitors of the glycoprotein IIb/IIIA.

Pregnancy and lactation:

The drug is contraindicated during pregnancy and lactation (breastfeeding).

Special instructions:

In patients with acute myocardial infarction with increased ST segment treatment with clopidogrel should not be started within the first few days after myocardial infarction.

In the absence of clinical data of clopidogrel is not recommended in acute ischemic stroke (less than 7 days).

With the development of bleeding during the treatment it is necessary to immediately carry out a clinical blood test (APTT, platelet count, tests of functional activity of platelets) and liver enzymes.

Like other antithrombotic drugs, clopidogrel should be used with caution in patients with increased risk of bleeding (particularly gastrointestinal and intraocular) due to trauma, surgery or pathological conditions, and in the case of combined use of clopidogrel with acetylsalicylic acid, NSAIDs, heparin, inhibitors of the glycoprotein IIb/IIIa or with thrombolytic drugs.

Noted severe cases of bleeding in patients, taking clopidogrel simultaneously with acetylsalicylic acid or with acetylsalicylic acid and heparin.

Clopidogrel increases bleeding time, so patients should be warned that because to stop appearing on the background of the drug (both as monotherapy and in combination with acetylsalicylic acid) bleeding takes a long time, you must inform your doctor about each case of bleeding. Patients should also inform the doctor and the dentist about the drug in the case of the upcoming surgery or if the doctor prescribes for the patient a new drug.

In the case of surgical interventions, if antiplatelet effect not desirable, treatment with clopidogrel should be discontinued 7 days before surgery.

Careful patient monitoring for signs of bleeding, including obscure bleeding, especially during the first weeks of treatment and/or after invasive cardiac procedures or surgery.

Effects on ability to drive vehicles and management mechanisms

The drug has no effect on the ability to drive vehicles and does not reduce the speed of psychomotor reactions.

Overdose:

Symptoms: may increase bleeding time.

Treatment: if necessary, a rapid correction of increased bleeding time effect of clopidogrel can be corrected by platelet transfusion. There is no specific antidote.

Drug interactions:

While the use of clopidogrel with warfarin may increase the intensity of bleeding (this combination is not recommended).

Acetylsalicylic acid does not alter the inhibitory effect of clopidogrel on ADP-induced platelet aggregation, but clopidogrel potentiates the effect of acetylsalicylic acid on platelet aggregation induced by collagen. However, the simultaneous use of acetylsalicylic acid at a dose of 500 mg 2 times/day did not cause any significant increase in bleeding time, prolonged as a result of clopidogrel. The safety of long-term concurrent use of acetylsalicylic acid and clopidogrel is not installed, however, the clopidogrel and acetylsalicylic acid can be applied simultaneously to one year.

According to clinical studies conducted in healthy volunteers, the simultaneous use of clopidogrel and heparin does not require dose adjustment of the latter and does not affect the antiplatelet effect of clopidogrel, however, the safety of such combinations have not yet installed (when this combination requires caution).

Safety of concurrent use with clopidogrel with thrombolytic drugs currently not installed (when this combination requires caution).

In a clinical study involving healthy volunteers, in a joint application for clopidogrel and naproxen, an increase in the number of hidden gastrointestinal bleeding. However, due to the lack of clinical studies of drug interactions with other NSAIDs is not currently installed, is there an increased risk of gastrointestinal bleeding with the use of other drugs in this group (combination of clopidogrel and an NSAID requires caution).

Clinically significant pharmacodynamic interactions when used together clopidogrel with atenolol and/or nifedipine have not been identified.

Pharmacodynamic activity Laperla virtually unchanged while the use of phenobarbital, cimetidine or estrogen.

The pharmacokinetic properties of digoxin or theophylline was not modified when used together with clopidogrel.

Antacids do not alter the absorption of clopidogrel.

Data obtained in studies with human liver microsomes, indicate that clopidogrel can inhibit the activity of izofermenta CYP2C9. As a result, may increase the concentration in blood plasma of certain drugs such as phenytoin and tolbutamide, because they are metabolized through CYP2C9. The results of the CAPRIE study indicate the safety of use of phenytoin and tolbutamide together with clopidogrel.

Terms and conditions of storage:

The drug should be stored out of reach of children at temperature not exceeding 30°C. shelf Life – 2.5 years.