Clopidogrel-Richter - instructions for use, dose, side effects, contraindications

excipients: tablet core: silicon dioxide colloid 3,000 mg, giprolose 18,000 mg, lactose 139.143 mg, croscarmellose sodium 24,000 mg, glyceryl dibehenate 18,000 mg; tablet shell: opadrai II yellow 31K32672 6,000 mg (composition obfuscated: hypromellose, type 2910 1.680 mg, lactose monohydrate 2,400 mg, titanium dioxide (E171) 1.346 mg, triacetin 0.480 mg, ferric oxide yellow oxide (E172) 0.094 mg).

Description:Round tablets of biconvex form, covered with a film coating of yellow color. The color of the core of the tablets at the break is white or almost white.

Pharmacotherapeutic group:antiplatelet agent

ATX: & nbsp

B.01.A. C.04 Clopidogrel

Pharmacodynamics:

Clopidogrel is a prodrug, one of the active metabolites of which is an inhibitor of platelet aggregation. The active metabolite of clopidogrel selectively inhibits the binding of ADP to P2Y12 receptor platelet and subsequent ADP-mediated activation of the complex GPIIb/IIIa, leading to suppression of platelet aggregation. Due to irreversible 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.

Since the formation of an active metabolite occurs with cytochrome P450 isoenzymes, some of which may be polymorphic or may be inhibited by other drugs, not all patients can adequately inhibit platelet aggregation.

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, on average, for 5 days.

Pharmacokinetics:

Suction. With a single and repeated oral administration at a dose of 75 mg per day clopidogrel quickly absorbed.

Mean values of maximum concentration (C_mOh) of unchanged clopidogrel in blood plasma (approximately 2.2-2.5 ng / ml after ingestion of a single dose of 75 mg) are reached approximately 45 minutes after taking the drug. According to excretion of metabolites of clopidogrel in 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 (by 98% and 94%, respectively) and this bond is unsaturated in a wide range of concentrations.

Metabolism. Clopidogrel intensively 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), and the second pathway through the cytochrome P450 system. Clopidogrel is metabolized to 2-oxo-clopidogrel, which is an intermediate metabolite. Subsequent metabolism of 2-oxo-clopidogrel leads to the formation of an active metabolite of clopidogrel-thiol clopidogrel derivative. In vitro this pathway of metabolism occurs with the help of isoenzymes CYP3A4, CYP2C19, CYP1A2 and CYP2B6. The active thiol metabolite of clopidogrel, which was isolated in in vitro studies,quickly and irreversibly binds to platelet receptors, blocking the aggregation of platelets.

FROM_max active metabolite of clopidogrel after receiving its loading dose of 300 mg is 2 times higher than C_mOh after 4 days of taking a maintenance dose of clopidogrel 75 mg. In this case, when taking 300 mg clopidogrel C_mOh is achieved within about 30-60 minutes.

Excretion. Within 120 hours after ingestion by a human ¹⁴C-labeled clopidogrel about 50% of the radioactivity is released through the kidneys (into the urine) and approximately 46% of the radioactivity is excreted through the intestine with a fecal mass. After a single oral dose of 75 mg, the half-life period (t_1/2) of clopidogrel is approximately 6 hours. After a single administration and reception of repeated doses of clopidogrel t_1/2its main circulating in the blood 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 in the study of platelet aggregation ex vivo vary depending on the genotype of the isoenzyme CYP2C19.The allele of the gene СUR2С19 * 1 corresponds to fully functional metabolism, whereas the alleles of the CYP2C19 * 2 and CYP2C19 * 3 genes are non-functional. Alleles of CYP2C19 * 2 and CYP2C19 * 3 genes cause a decrease in metabolism in the majority of representatives of the Caucasoid (85%) and Mongoloid (99%). Other alleles associated with lack or decrease in metabolism are less common and include CYP2C19 * 4, * 5, * 6, * 7 and * 8. Patients with a low activity of the isoenzyme CYP2C19 should have the two alleles of the loss-of-function gene mentioned above. Published frequency of occurrence of phenotypes of persons with low activity of the isoenzyme CYP2C19 is 2% for Caucasians, 4% for Negroid people and 14% for Chinese. There are corresponding tests to determine the patient's genotype of the CYP2C19 isoenzyme.

According to the study, patients with moderate or low metabolic status had a higher incidence of cardiovascular complications (death, myocardial infarction and stroke) or stent thrombosis compared to patients with intensive metabolism.

Pharmacokinetics in special clinical cases

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, there was no difference in platelet aggregation and bleeding time.

Impaired renal function

After repeated administration of 75 mg clopidogrel per day in individuals with severe renal dysfunction (creatinine clearance 5-15 ml / min), inhibition of ADP-induced platelet aggregation was less pronounced (25%) than in healthy volunteers, however, the bleeding time was similar to that of healthy volunteers who received 75 mg of clopidogrel per day. The tolerability of the drug was good in all patients.

Impaired liver function

After repeated administration of 75 mg clopidogrel per day for 10 days in patients with severe liver dysfunction, inhibition of ADP-induced platelet aggregation was similar to that of healthy volunteers. The average bleeding time was also similar.

Race

Prevalence of alleles of isoenzyme genes CYP2C19, responsible for the intermediate and decreased metabolism of clopidogrel to its active metabolite, varies depending on race / ethnicity.There are limited data on representatives of the Mongoloid race, which allow one to assess the clinical significance of genotyping of this CYP from the point of view of the clinical effect.

Indications:

Prevention of atherothrombotic complications:

- in adult patients with myocardial infarction (with a duration of several days to 35 days), ischemic stroke (with a duration of 7 days to 6 months) or diagnosed by occlusive disease of peripheral arteries;

- in adults with 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); with ST segment lift (acute myocardial infarction) with drug treatment and the possibility of carrying out thrombolysis (in combination with acetylsalicylic acid).

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

In patients with atrial fibrillation (atrial fibrillation),which have at least one risk factor for vascular complications, can not take indirect anticoagulants and have a low risk of bleeding (in combination with acetylsalicylic acid).

Contraindications:

- Hypersensitivity to the components of the drug;

severe hepatic impairment;

- Acute bleeding,for example, bleeding from a peptic ulcer or intracranial hemorrhage;

- Rcaustic hereditary lactose intolerance, lactase deficiency and glucose-galactose malabsorption syndrome;

- pregnancy and lactation period (see the section "Application during pregnancy and lactation");

- age up to 18 years (efficacy and safety of use not established).

Carefully:

Moderate hepatic and / or renal insufficiency;

- pathological conditions that increase the risk of bleeding (including trauma, surgical interventions);

- diseases in which there is a predisposition to the development of bleeding (especially gastrointestinal or intraocular);

- simultaneous administration of non-steroidal anti-inflammatory drugs (including selective inhibitors of cyclooxygenase-2 (COX-2)), warfarin, heparin and glycoprotein inhibitors IIb/IIIa; in patients with low isoenzyme activity CYP2C19 (since they have less active metabolite of clopidogrel in recommended doses at recommended doses, and its antiplatelet effect is less pronounced, and therefore, when taking the usually recommended doses of clopidogrel in acute coronary syndrome or percutaneous coronary intervention, a higher incidence of cardiovascular complications is possible , than in patients with normal isoenzyme activity CYP2C19).

Pregnancy and lactation:

BVariability

Since there are no clinical data on the use of the drug during pregnancy, it is not recommended to take Clopidogrel-Richter during pregnancy. Experimental studies in animals showed no direct or indirect adverse effects on the course of pregnancy, embryonic development, childbirth, or postnatal development.

Lactation period

It is not known whether the clopidogrel in human milk. In animal studies, it was shown that clopidogrel and / or its metabolites are excreted into breast milk, so breast-feeding in case of treatment with clopidogrel should be discontinued.

Dosing and Administration:

Clopidogrel-Richter should be taken orally, regardless of food intake.

Adults and elderly patients with normal isoenzyme activity CYP2C19

With myocardial infarction, ischemic stroke and diagnosed occlusive disease of peripheral arteries

The drug is taken 75 mg once at day.

In patients with myocardial infarction, treatment can start from the first days to 35 days of myocardial infarction, and in patients with ischemic stroke - in the period from 7 days to 6 months after an ischemic stroke.

In acute coronary syndrome:

- without segment elevation ST (unstable angina or myocardial infarction without a tooth ABOUT) Treatment with Clopidogrel-Richter should be started with a single loading dose of 300 mg (4 tablets), and then continue taking the drug at a dose of 75 mg once a day (in combination with acetylsalicylic acid at doses of 75-325 mg per day). Since the use of higher doses of acetylsalicylic acid is associated with an increased risk of bleeding, the recommended dose of acetylsalicylic acid should not exceed 100 mg. The optimal duration of treatment is not officially defined.Clinical trials support the use of the drug for up to 12 months, and the maximum beneficial effect was observed by the third month of treatment.

- with segment lift ST (acute myocardial infarction with segment elevation ST): Clopidogrel-Richter should be taken once a day at a dose of 75 mg with the initial single dose of a loading dose of clopidogrel 300 mg (4 tablets) in combination with acetylsalicylic acid in combination with thrombolytic agents or without thrombolytic agents. In patients older than 75 years, treatment with Clopidogrel-Richter should begin without taking a loading dose. Combination therapy should be started as soon as possible after the onset of symptoms and last at least four weeks. The effectiveness of the combination of Clopidogrel-Richter and acetylsalicylic acid at this indication for more than 4 weeks has not been studied.

When atrial fibrillation (atrial fibrillation)

Clopidogrel-Richter should be taken once a day at a dose of 75 mg. In combination with the Clopidogrel-Richter preparation, it is necessary to start and then continue taking acetylsalicylic acid (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).

Patients with genetically determined reduced isoenzyme activity CYP2C19

The low activity of the isoenzyme CYP2C19 is associated with a decrease in the antiplatelet effect of clopidogrel. The mode of application of higher doses (600 mg - loading dose, then 150 mg once a day daily) in patients with low isoenzyme activity CYP2C19 increases the antiplatelet effect of clopidogrel. However, at the present time in clinical studies that take into account clinical outcomes, an optimal dosing regimen for clopidogrel has not been established for patients with reduced metabolism due to genetically determined low isoenzyme activity CYP2C19.

Special patient groups

Elderly patients

Do not require dose adjustment for the elderly.

Children

There is no experience of using the drug in children.

Patients with impaired renal function

The experience of using in patients with impaired renal function is limited.

Patients with impaired hepatic function

The experience of using in patients with liver diseases of moderate severity (in which there may be manifestations of hemorrhagic diathesis) is limited.

Side effects:

The frequency of adverse reactions that were observed during clinical trials or were obtained from spontaneous reports on the development of adverse reactions is determined as follows: often (≥1/100 - <1/10); infrequently (≥1/1000 - <1/100); rarely (≥1/10 000 - <1/1000); very rarely (<1/10 000). In each system-organ class, undesirable reactions are presented in order of decreasing severity.

Violations of the blood and lymphatic system

Infrequent: thrombocytopenia, leukopenia, eosinophilia.

Rarely: neutropenia, including severe neutropenia.

Very rarely: thrombotic thrombocytopenic purpura TTL (see section "Special instructions"), aplastic anemia, pancytopenia, agranulocytosis, severe thrombocytopenia, granulocytopenia, anemia.

Immune system disorders

Very rarely: serum sickness, anaphylactoid reactions.

Disorders of the psyche

Very rarely: hallucinations, confusion.

Disturbances from the nervous system

Infrequently: intracranial hemorrhage (several cases with fatal outcome were reported), headache, paresthesia, dizziness.

Very rarely: a violation of taste perception.

Disturbances on the part of the organ of sight

Infrequent: hemorrhage in the eyes (conjunctival, in the tissue and retina of the eye). Hearing disorders and labyrinthine disorders Rarely: vertigo.

Vascular disorders

Often: hematoma.

Very rarely: serious bleeding from the operating wound, vasculitis, lowering blood pressure.

Disturbances from the respiratory system, chest and mediastinal organs

Often: nosebleeds.

Very rarely: bleeding from the respiratory tract (hemoptysis, pulmonary hemorrhage), bronchospasm, interstitial pneumonia.

Disorders from the gastrointestinal tract

Very often: gastrointestinal bleeding, diarrhea, abdominal pain, indigestion.

Uncommon: ulcer of the stomach and duodenum, gastritis, vomiting, nausea, constipation, bloating.

Rarely: retroperitoneal hemorrhage.

Very rarely: gastrointestinal bleeding and retroperitoneal hemorrhage with fatal outcome, pancreatitis, colitis (including ulcerative colitis or lymphocytic colitis), stomatitis.

Disturbances from the liver and bile ducts

Very rarely: acute liver failure, hepatitis, deviation from the norm of indicators of functional "liver" tests.

Disturbances from the skin and subcutaneous tissues

Often: subcutaneous bruising.

Infrequent: rash, itching, purpura (subcutaneous hemorrhage).

Very rarely: bullous dermatitis (toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme) angioedema, erythematous rash, urticaria, eczema, flat lichen.

OnCollapse of musculoskeletal system and connective tissue

Very rarely: hemorrhages in the muscles and joints (hemarthrosis), arthritis, arthralgia, myalgia.

Disorders from the kidneys and urinary tract

Infrequently: hematuria.

Very rarely: glomerulonephritis, an increase in the concentration of creatinine in the blood. General disorders and disorders in place introduction.

Often: bleeding at the injection / puncture site.

Very rarely: fever.

Laboratory and instrumental data

Infrequent: increased bleeding time, a decrease in the number of neutrophils, a decrease in the number of platelets in the peripheral blood.

Overdose:

Symptoms: an overdose of clopidogrel may lead to an increase in bleeding time with subsequent complications in the form of development of bleeding.

Treatment: when bleeding occurs, appropriate treatment is required. The antidote of clopidogrel is not established. If rapid correction of prolonged time of bleeding is necessary, then transfusion of platelet mass is recommended.

Interaction:

The simultaneous use of clopidogrel with oral anticoagulants is not recommended, since this combination may increase the intensity of bleeding (see section "Special instructions"). Despite the fact that taking clopidogrel at a dose of 75 mg per day did not change the pharmacokinetics S-varmarin or MNO (international normalized ratio) in patients who are long-treated with warfarin, concurrent administration of clopidogrel increases the risk of bleeding due to its independent additional effect on blood clotting.

Inhibitors of glycoprotein IIb/IIIa: use of glycoprotein IIb / IIIa inhibitors in conjunction with clopidogrel requires caution in patients who have an increased risk of bleeding (with trauma and surgical interventions or other pathological conditions) (see section "Special instructions").

Acetylsalicylic acid (ASA): acetylsalicylic acid does not affect the inhibition of ADP-induced platelet aggregation by clopidogrel, but clopidogrel potentiates the effect of ASA on collagen-induced aggregation of platelets. However, simultaneous with clopidogrel, the administration of ASA at a dose of 500 mg twice daily for one day did not significantly prolong the bleeding time caused by the use of clopidogrel. Between clopidogrel and ASA, pharmacodynamic interaction is possible, which leads to an increased risk of bleeding. Given this, caution should be exercised while using these medications simultaneously, although there has been experience in sharing clopidogrel and ASA for one year.

Heparin: simultaneous use of clopidogrel and heparin does not require correction of the dose of the latter and does not affect the antiplatelet effect of clopidogrel,However, between clopidogrel and heparin, pharmacodynamic interaction is possible, which may increase the risk of bleeding, so the simultaneous use of these drugs requires caution.

Thrombolytics: the safety of the combined use of clopidogrel, fibrin-specific or fibrin-nonspecific thrombolytic drugs and heparin was investigated in patients with acute myocardial infarction. The frequency of clinically significant bleeding was similar to that observed in the joint use of thrombolytic agents and heparin with acetylsalicylic acid.

Non-steroidal anti-inflammatory drugs (NSAIDs)): it is known that the simultaneous use of clopidogrel and naproxen increased the frequency of latent gastrointestinal bleeding. However, due to the lack of studies on the interaction of clopidogrel with other NSAIDs, it is not currently known whether there is an increased risk of developing gastrointestinal bleeding when taking clopidogrel together with other NSAIDs. Therefore, care should be taken when using clopidogrel with NSAIDs simultaneously, including COX-2 inhibitors (see Table 1).section "Special instructions").

Other concurrent drugs

As clopidogrel metabolized to the formation of its active metabolite in part by means of isoenzyme CYP2C19, the use of drugs that inhibit this system can lead to a decrease in the concentration of the active metabolite clopidogrel. The clinical significance of this interaction is not established. It should avoid simultaneous use with clopidogrel powerful or moderate inhibitors of isoenzyme CYP2C19 (see the section "Pharmacokinetics, subsection Pharmacogenetics", section "Special instructions"). To drugs that inhibit isoenzyme activity CYP2C19, are: omeprazole and esomeprazole, fluvoxamine, fluoxetine, moclobemide, voriconazole, fluconazole, ticlopidine, ciprofloxacin, cimetidine, carbamazepine, oxcarbazepine and chloramphenicol.

Proton Pump Inhibitors: taking omeprazole 80 mg once a day with clopidogrel or 12 hours after taking clopidogrel reduced the concentration of the active metabolite by 45% (after taking a loading dose of clopidogrel) and by 40% (after taking a maintenance dose of clopidogrel).This decrease was accompanied by a 39% decrease (after taking a loading dose of clopidogrel) and 21% (after taking a maintenance dose of clopidogrel) inhibitory effect on platelet aggregation. It is believed that esomeprazole interacts with clopidogrel in a similar manner.

The simultaneous use of omeprazole and esomeprazole with clopidogrel.

A less pronounced decrease in the metabolite concentration is observed when pantoprazole or lansoprazole.

With the simultaneous use of pantoprazole at a dose of 80 mg once a day, the concentration of the active metabolite in the blood plasma was reduced by 20% (after taking a loading dose of clopidogrel) and by 14% (after taking a maintenance dose of clopidogrel). This was accompanied by a 15% decrease in the inhibitory effect on platelet aggregation and 11%, respectively.

If proton pump inhibitors are to be taken concomitantly with clopidogrel, a proton pump inhibitor with the least inhibition of isoenzyme CYP2C19, such as pantoprazole.

There is no evidence that other drugs that reduce the secretion of acid in the stomach, such as H₂-blocks (with the exception of cimetidine, which is an inhibitor of the isoenzyme CYP2C19) or antacids affect the antiplatelet activity of clopidogrel.

Simultaneous reception with other drugs

There were no clinically significant interactions with concomitant use with atenolol, angiotensin-converting enzyme (ACE) inhibitors, nifedipine, digoxin, phenobarbital, cimetidine, estrogen, theophylline, thrombolytics, diuretics, beta-blockers, slow calcium channel blockers, lipid-lowering agents, coronary vasodilators, hypoglycemic agents (including insulin), antiepileptic means, hormone replacement therapy and inhibitors of glycoprotein IIb / IIIa.

Antacid agents did not reduce the absorption of clopidogrel Phenytoin and tolbutamide can be safely used simultaneously with clopidogrel. It is unlikely that clopidogrel can influence the metabolism of other medicines, such as phenytoin and tolbutamide, as well as non-steroidal anti-inflammatory drugs that are metabolized by isoenzyme CYP2C9 family of cytochrome P450.

Special instructions:

When Clopidogrel-Richter is used, especially during the first weeks of therapy and / or after invasive cardiac procedures / surgery, patients should be closely monitored for the exclusion of signs of bleeding, including concealed bleeding.

When clinical symptoms appear that indicate the occurrence of bleeding, it is necessary to urgently do a clinical blood test, determine activated partial thromboplastin time (APTT); the number of platelets, the indicators of the functional activity of platelets and conduct other necessary studies.

Clopidogrel-Richter should be used with caution in patients who have an increased risk of bleeding due to trauma, surgery or other pathological conditions, also in patients receiving ASA, heparin, Ilb / IIIa glycoprotein inhibitors or NSAIDs, including COX inhibitors -2. Treatment with Clopidogrel-Richter should be stopped at least 7 days before the planned surgical intervention (including dental procedures).Patients should inform the doctor (including the dentist) about taking Clopidogrel-Richter before performing any invasive operation and before starting any new drug. Simultaneous use of the Clopidogrel-Richter preparation and internal anticoagulants is not recommended because of the possible increase in the intensity of bleeding (see section "Interaction with other drugs").

Clopidogrel-Richter prolongs bleeding time and should be used with caution in patients with diseases predisposing to the development of bleeding (especially, gastrointestinal and intraocular). Drugs that can cause damage to the gastrointestinal mucosa (such as ASA, NSAIDs) in patients receiving clopidogrel, should be used with caution. Patients should be warned that with the use of Clopidogrel-Richter (in monotherapy or in combination with ASA), it may take longer to stop bleeding, and that if they have an unusual (localized or prolonged) bleeding should inform your doctor about it.

In very rare cases, when taking clopidogrel (sometimes even a short one), there were cases of thrombotic thrombocytopenic purpura (TTP). TTP is characterized by thrombocytopenia and microangiopathic hemolytic anemia, accompanied by neurological disorders, impaired renal function and fever. TTP is a condition that potentially threatens the patient's life and requires immediate therapy, including plasmapheresis.

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

Clopidogrel-Richter is not recommended for use during the first 7 days of acute ischemic stroke (not enough clinical data).

In the case of small cuts (for example, shaving) and injuries, no special measures are usually required. For large cuts or injuries, immediate medical attention is needed.

In patients with genetically reduced isoenzyme activity CYP2C19 there is a lower concentration of the active metabolite of clopidogrel in the blood plasma, which is associated with a decrease in the antiplatelet effect of clopidogrel.In this category of patients, cardiovascular complications are significantly more likely after myocardial infarction compared with patients with normal isoenzyme activity CYP2C19 (see the section "Pharmacological action").

Because the clopidogrel metabolized to the active metabolite partially under the action of the isoenzyme CYP2C19, the use of drugs that reduce the activity of this isoenzyme can lead to a decrease in the concentration of the active metabolite of clopidogrel in the blood plasma and to a decrease in the clinical effect of clopidogrel. It should avoid simultaneous use of drugs that are potent or moderate inhibitors of the isoenzyme CYP2C19 (see the list of inhibitors of isoenzyme CYP2C19 in the section "Interaction with other medicinal products"). Clopidogrel-Richter should not be taken to patients with such rare hereditary diseases as lactose intolerance, lactase deficiency and glucose-galactose malabsorption syndrome (see the sections "Composition" and "Contraindications").

Effect on the ability to drive transp. cf. and fur:

Clopidogrel-Richter does not have a significant impact on the ability to drive vehicles or work withmechanisms.

Form release / dosage:Tablets coated with a film coating, 75 mg.

Packaging:

For 14 tablets in a blister of solid aluminum foil and solid white opaque PVC / PTFE / PVC foil.

For 1 or 2 blisters together with instructions for use in a cardboard box.

Storage conditions:Store in a dry, dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-001976

Date of registration:23.01.2013

The owner of the registration certificate:GEDEON RICHTER, OJSC GEDEON RICHTER, OJSC Hungary

Manufacturer: & nbsp

GEDEON RICHTER ROMANIA, S.A. Romania

Representation: & nbspGEDEON RICHTER OJSC GEDEON RICHTER OJSC Hungary

Information update date: & nbsp02.08.2015

Illustrated instructions

Instructions

Clopidogrel-Richter (Clopidogrel-Richter)