LOPIREL

Active material: Clopidogrel
When ATH: B01AC04
CCF: Antiplatelet
ICD-10 codes (testimony): I20.0, I21, I63, I74, I82
When CSF: 01.12.11.06.01
Manufacturer: ACTAVIS GROUP hf. (Iceland)

PHARMACEUTICAL FORM, COMPOSITION AND PACKAGING

Pills, Film-coated Pink colour, round, lenticular, Engraved “I” on one side.

Excipients: lactose, microcrystalline cellulose, krospovydon (type A), glyceryl dibegenat, talc, Opadry II 85 G34669 pink (polyvinyl alcohol, talc, Titanium dioxide (E171), macrogol 3350, lecithin (E322), iron oxide red dye (E172)).

7 PC. – blisters (4) – packs cardboard.

Pharmacological action

antiplatelet agent, specific and active inhibitor of platelet aggregation. Has a coronary dilating effect. Selectively reduces the binding of ADP to platelet receptors and the activation of GPI Ib/IIIa receptors under the influence of ADP, reducing, thus, platelet aggregation. It reduces platelet aggregation, induced by other agonists, preventing them from activating released ADP, does not affect PDE activity. It binds irreversibly to platelet ADP receptors, which remain impervious to ADP stimulation lifecycle (about 7 days).

Inhibition of platelet aggregation is a 2 h after administration (40% inhibition of) initial dose 400 mg. Maximum effect (60% Suppression of aggregation) develops through 4-7 days of admission to the dose of 50-100 mg / day. Antiagregantnyj effect is the entire period of the life of platelets (7-10 days).

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

Pharmacokinetics

Absorption

Absorption vыsokaya, bioavailability is high; The plasma concentration is low and by 2 h after administration reaches the measurement limit (0.025 ug / l).

Distribution

Plasma protein binding – 94-98%.

Metabolism

It is metabolized in the liver. The major metabolite – inactive derivative of a carboxylic acid. After oral administration in repeated doses 75 mg C_max metabolite in blood plasma is about 3 mg / l and is achieved through the 1 no.

Deduction

Report the news - 50%, through the intestine – 46% (during 120 hours after injection). T_1/2 the main metabolite after a single and repeated dose is 8 no. Concentrations of renal metabolites – 50%.

Pharmacokinetics in special clinical situations

After taking the drug at a dose 75 mg/day plasma concentrations of the main metabolite are lower in patients with severe kidney disease (CC 5-15 ml / min), compared to patients with kidney disease of moderate severity (KK from 30 to 60 ml / min) and healthy individuals.

Testimony

Prevention of atherothrombosis:

-in patients, myocardial infarction, ischemic stroke, or with diagnosed peripheral artery disease;

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

Dosage regimen

The drug is prescribed inside of 75 mg 1 time / day regardless of the meal.

Treatment should begin within the period of a few days before 35 days in patients myocardial infarction and by 7 days before 6 months in patients After ischemic stroke.

Patients with acute coronary syndrome without ST segment elevation (unstable angina or myocardial infarction without a Q wave on the ECG) treatment with Lopirel is started with a single dose 300 mg, and then continue at the dose 75 mg 1 time / day (with acetylsalicylic acid in a dose 75-325 mg / day). The optimal duration of treatment has not been established. Treatment lasting up to 12 Months, the maximum effect is observed after 3 months after initiation of treatment.

Side effect

Determination of the frequency of adverse reactions: often (>1/100, <1/10), sometimes (>1/1000, <1/100), rarely (>1/10 000, <1/1000), rarely (<1/10 000).

CNS: sometimes – headache, dizziness, paraesthesia; rarely – confusion, hallucinations, dysgeusia.

From the digestive system: often – dyspepsia, abdominal pain, diarrhea; sometimes – nausea, gastritis, flatulence, constipation, vomiting, peptic ulcer; rarely – colitis (incl. ulcerative or lymphocytic), pancreatitis.

From the hepatobiliary system: rarely – hepatitis, increase in liver transaminases.

From the hematopoietic system: sometimes – leukopenia, decrease in the number of neutrophil and eosinophil granulocytes, reduction in the number of platelets; rarely – tyazhelaya thrombocytopenia (platelet count ≤30-10⁹/l), granulocytopenia, agranulocytosis, anemia and aplastic anemia/pancytopenia.

From the blood coagulation system: sometimes – increase in bleeding time; rarely – tromboticheskaya trombotsitopenicheskaya purpura (1 case of 200 000 patients); often – bleeding of varying localization and intensity. Most cases of bleeding were noted during the 1st month of treatment (especially intracranial, gastrointestinal and retroperitoneal haemorrhage); severe cases of skin bleeding (purpura), hemorrhages in joints and soft tissues (gemartroz, hematoma), eye bleeding (conjunctival, ocular, retinal), nosebleeds, from the respiratory tract (hemoptysis, pneumorrhagia), hematuria and bleeding from the surgical wound.

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

Allergic reactions: rarely – hives, anaphylactoid reactions.

Cardio-vascular system: rarely – vasculitis, hypotension.

The respiratory system: rarely – bronchospasm.

On the part of the musculoskeletal system: rarely – arthralgia, arthritis.

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

Other: rarely – fever.

Contraindications

- Severe hepatic impairment;

- Hemorrhagic syndrome;

- Severe bleeding (incl. intracranial hemorrhage) and disease, predispose to its development (gastric ulcer and duodenal ulcer in the acute phase, nespetsificheskiy yazvennыy colitis, tuberculosis, lung tumor, giperfiʙrinoliz);

- Pregnancy;

- Lactation (breast-feeding);

- neonatal period;

- Up to 18 years (efficacy and safety have not been established);

- Galactose intolerance, lactase deficiency or glucose-galactose malabsorption (tk. the composition of the drug includes lactose);

- Hypersensitivity to the drug.

FROM caution the drug should be used in patients with moderate hepatic and/or renal impairment, trauma, Preoperative; simultaneously with acetylsalicylic acid, NSAIDs (including COX-2 inhibitors), varfarinom, thrombolytic agents, geparinom, glycoprotein IIb/IIIa inhibitors.

Cautions

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

Due to the lack of clinical data, clopidogrel is not recommended for use in acute ischemic stroke. (less 7 days).

If bleeding develops during treatment with the drug, a clinical blood test must be immediately performed. (APTT, platelet count, Platelet function tests) and functional activity of the liver.

Similar to other antithrombotic drugs, clopidogrel should be used with caution in patients at increased risk of bleeding (particularly gastrointestinal and intraocular) due to injury, surgical interventions or pathological conditions, and also in the case of combined use of clopidogrel with acetylsalicylic acid, NSAIDs, geparinom, glycoprotein IIb/IIIa inhibitors or thrombolytics.

Severe cases of bleeding have been reported in patients, clopidogrel together with acetyl salicylic acid or acetylsalicylic acid and heparin.

Clopidogrel increases bleeding time, Therefore, patients should be warned about, that since in order to stop what occurs during the use of the drug (as a monotherapy, and in combination with acetylsalicylic acid) bleeding takes a long time, It is necessary to inform the doctor about each case of bleeding. Patients should also inform the doctor and dentist about taking the drug in case of upcoming surgery or if the doctor prescribes a new drug for the patient..

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

Careful monitoring of patients is necessary for signs of bleeding, including hidden bleeding, especially during the first weeks of treatment and/or after invasive cardiac procedures or surgery.

Pharmacokinetics in special clinical situations

The drug does not affect the ability to drive vehicles and does not reduce the speed of psychomotor reactions.

Overdose

Symptoms: may increase bleeding time.

Treatment: if rapid correction of prolonged bleeding time is necessary, the effect of clopidogrel can be eliminated by platelet transfusion. No specific antidote

Drug Interactions

When clopidogrel is used concomitantly with warfarin, bleeding may increase. (this combination is not recommended).

Acetylsalicylic acid does not change the inhibitory effect of clopidogrel on ADP-induced platelet aggregation, however, clopidogrel potentiates the effect of acetylsalicylic acid on platelet aggregation, collagen-induced. Nonetheless, simultaneous use of acetylsalicylic acid in a dose 500 mg 2 times/day did not cause any significant increase in bleeding time, prolonged due to taking clopidogrel. The safety of long-term simultaneous use of acetylsalicylic acid and clopidogrel has not been established., however, clopidogrel and acetylsalicylic acid can be used simultaneously for up to one year.

According to a clinical study, conducted on healthy volunteers, 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 this combination has not yet been established (Caution is required with this combination).

The safety of simultaneous use of clopidogrel with thrombolytics has not yet been established. (Caution is required with this combination).

In a clinical study, held with the participation of healthy volunteers, When clopidogrel and naproxen were used together, an increase in the number of occult gastrointestinal bleedings was observed. However, due to the lack of clinical studies, the interaction of the drug with other NSAIDs has not yet been established., is there an increased risk of gastrointestinal bleeding when using other drugs in this group (Caution is required when combining clopidogrel and NSAIDs).

No clinically significant pharmacodynamic interaction was detected when clopidogrel was used in combination with atenolol and/or nifedipine..

The pharmacodynamic activity of Lopirel remains virtually unchanged when used simultaneously with phenobarbital, cimetidine or estrogens.

The pharmacokinetic properties of digoxin or theophylline do not change when used together with clopidogrel.

Antacids do not alter the absorption of clopidogrel.

Data, obtained in the course of studies with human liver mikrosomami, indicates, that clopidogrel can inhibit the activity of the CYP2C9 isoenzyme. As a result, plasma concentrations of some drugs may increase, such as phenytoin and tolbutamide, as they are metabolized by CYP2C9. CAPRIE study results indicate safety of phenytoin and tolbutamide combined with clopidogrel.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

The drug should be stored out of reach of children at or above 30 ° C. Shelf life – 2.5 year.