Cardogrel - instructions for use, dose, side effects, contraindications

tablet core: active ingredient: clopidogrel hydrogensulfate * 97.875 mg (expressed as clopidogrel 75,000 mg); Excipients: mannitol 125,375 mg, microcrystalline cellulose 50,500 mg, giprolose (with a low degree of substitution) 20,250 mg, vegetable oil hydrogenated 6,000 mg;

film sheath: opadrai pink (03V54942) 9,000 mg, water ** q.s .;

Ink for labeling a tablet: opaque S-1-17823 black q.s.

* Clopidogrel hydrogensulfate (Form I)

** Not included in the final product

Composition of Otpadra pink (03В54942) (% m / m): hypromellose (2910) 6 cp 63,650, titanium dioxide 29,477, macrogol-400 6,300, iron dye oxide red 0.573,

The composition of Opacode S-1-17823 black (% m / m): shellac 45% (esterification 20%) in ethanol 44,467, dye iron oxide black 23,409, n-butanol 2,242, propylene glycol 2,000, isopropanol 26,882, ammonium hydroxide 28% 1,000.

Description:

Round biconvex tablets covered with a pink film cover, with an inscription of black ink "SZ / 75" on one side.

On the cross section, the core of the tablet is white.

Pharmacotherapeutic group:antiplatelet agent

ATX: & nbsp

B.01.A. C.04 Clopidogrel

Pharmacodynamics:

Antiaggregant agent. It is a prodrug, one of the active metabolites of which is an inhibitor of platelet aggregation. Selectively inhibits the binding of adenosine diphosphate (ADP) to platelet ADP receptors and subsequent activation of the glycoprotein receptor complex GPIIb/IIIa under the action of ADP, thereby suppressing ADP-induced platelet aggregation.Irreversibly binds to ADP-receptor platelets, which remain immune to ADP stimulation throughout the rest of their life (approximately 7-10 days). Restoration of normal function of platelets 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 the active metabolite occurs with the participation of P450 isoenzymes, some of which are polymorphic or inhibited by other drugs, adequate platelet suppression is not possible in all patients.

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 (upon reaching the equilibrium state). 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 tothe baseline on average for 5 days.

Pharmacokinetics:

After a single or repeated oral administration of 75 mg / day clopidogrel quickly absorbed from the gastrointestinal tract (GIT). 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 after approximately 45 minutes. According to excretion of metabolites of clopidogrel with urine, its absorption is at least 50%.

Clopidogrel is rapidly metabolized in the liver with the formation of active and inactive metabolites.

Clopidogrel is a prodrug. An active metabolite, a thiol derivative, is formed by oxidizing clopidogrel to 2-oxoclopidogrel and subsequent hydrolysis. In vitro this pathway of metabolism occurs by means of isoenzymes CYP3A4, CYP2C19, CYP1A2 and CYP2B6. Active thiol metabolite, isolated in vitro, quickly and irreversibly binds to platelet receptors, as a result of which blocks their aggregation. The main metabolite of clopidogrel (a carboxylic acid derivative), which is about 85% of the substance circulating in the plasma, has no pharmacological activity.

The kinetics of the main circulating metabolite is linear in the dose range of 50-150 mg of clopidogrel.

Clopidogrel and its main circulating metabolite in vitro reversibly bind to human plasma proteins (98% and 94%, respectively).

Within 120 hours after ingestion, about 50% of the dose is excreted by the kidneys, and approximately 46% of the dose taken is through the intestine.

After a single oral dose of 75 mg half-life (T_1/2) of clopidogrel is approximately 6 hours. T_1/2the main circulating (inactive) metabolite is 8 hours after a single or repeated administration.

In patients with severe renal insufficiency (SC 5-15 ml / min) after repeated clopidogrel administration in a dose of 75 mg / day, the initiation of ADP-induced platelet aggregation was lower (25%) compared to that of healthy volunteers, but the prolongation of the bleeding time was similar to that of healthy volunteers who received clopidogrel in a dose of 75 mg / day. Clinical tolerance of the drug was good in all groups of patients.

Pharmacogenetics

Using isoenzyme CYP2C19 are formed as an active metabolite, as well as an intermediate metabolite - 2-oxo-clopidogrel.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. Gene allele CYP2C19 * 1 corresponds to fully functional metabolism, whereas gene alleles CYP2C19 * 2 and CYP2C19 * 3 are non-functional. Alleles of genes CYP2C19 * 2 and CYP2C19 * 3 cause a decrease in metabolism in the majority of representatives of the Caucasoid (85%) and Mongoloid races (99%). Other alleles that are associated with a lack or decrease in metabolism are less common and include, but are not limited to, gene alleles CYP2C19 * 4, * 5, * 6, * 7 and * 8. Patients with low isoenzyme activity CYP2C19 should have the two alleles of the gene with loss of function. Published frequencies of occurrence of phenotypes of persons with low isoenzyme activity CYP2C19 are 2% in Caucasians, 4% in Negroid people and 14% in Chinese. To determine the patient's isoenzyme genotype CYP2C19 there are corresponding tests. There were no significant differences in the exposure of the active metabolite and in the mean platelet aggregation inhibition (IAT) (induced by ADP) in volunteers with very high, high and intermediate isoenzyme activity CYP2C19 was not identified.In volunteers with low isoenzyme activity CYP2C19, the exposure of the active metabolite decreased compared to volunteers with high isoenzyme activity CYP2C19. When volunteers with low isoenzyme activity CYP2C19 received a treatment regimen of 600 mg loading dose / 150 mg maintenance dose (600 mg / 150 mg), the exposure of the active metabolite was higher than when taking the 300 mg / 75 mg treatment regimen. In addition, the value of IAT was similar to that in groups of patients with a higher metabolic rate by isoenzyme CYP2C19, who received a treatment regimen of 300 mg / 75 mg. However, in studies with clinical outcomes, the dosage regimen of clopidogrel for patients with low isoenzyme activity CYP2C19 is not yet installed.

Indications:

Prevention of atherothrombotic complications in patients with myocardial infarction (from several to 35 days after the onset), ischemic stroke (with a duration of 7 days to 6 months), or occlusion of peripheral arteries.

In combination with acetylsalicylic acid for the prevention of atherothrombotic complications in acute coronary syndrome:

- with the rise of the segment of ST (with acute myocardial infarction) with the possibility of carrying out thrombolytic therapy;

- without ST segment elevation (unstable angina, myocardial infarction without Q wave), including in patients who underwent stenting with percutaneous coronary intervention;

Prevention of atherothrombotic and thromboembolic complications, including stroke, 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 active ingredient or any other component of the drug;

- severe hepatic impairment;

- acute bleeding, eg bleeding from peptic ulcers or intracranial hemorrhage;

- pregnancy and lactation;

- children under 18 years of age (safety and efficacy not established).

Carefully:

- With moderate hepatic insufficiency, which may predispose to bleeding (limited clinical experience of use);

- with renal failure (limited clinical experience of use);

- with injuries, surgical interventions (see section "Special instructions");

- at diseases at which there is a predisposition to development of bleedings (especially gastrointestinal or intraocular);

- with the simultaneous administration of non-steroidal anti-inflammatory drugs (NSAIDs), incl. selective inhibitors of cyclooxygenase-2 (COX-2);

- with the simultaneous use of oral anticoagulants, heparin, glycoprotein inhibitors IIb/IIIa, selective serotonin reuptake inhibitors (SSRIs);

- patients with low activity of the isozyme CYP2C19 (such patients with clopidogrel at recommended doses produce less active metabolite of clopidogrel and weaker expressed its antiplatelet effect, and therefore when receiving normally recommended dose of clopidogrel in acute coronary syndrome or percutaneous coronary intervention can be a higher frequency of cardiovascular complications than in patients with normal activity of the isoenzyme CYP2C19);

- at the instructions in the anamnesis for allergic and hematological reactions to other thienopyridines (ticlopidine, prasugrel) (see section "Special instructions");

- with a recent transient impairment of cerebral circulation or ischemic stroke (see section "Special instructions").

Pregnancy and lactation:

Studies in animals showed no direct or direct adverse effects on pregnancy, embryonic development, childbirth, and postnatal development. However, due to the lack of clinical data on the use of clopidogrel in pregnant women, the use of the drug in pregnancy is contraindicated.

It is not known whether the clopidogrel in human milk. In animal studies, it was shown that clopidogrel excreted in breast milk. The use of the drug in the period of breastfeeding is contraindicated.

Dosing and Administration:

The drug Cardogrel® is used by the doctor's prescription, inside, regardless of food intake.

Adults and elderly patients with normal activity of the isoenzyme CYP2C19

Prevention of thrombotic complications in patients with myocardial infarction, ischemic stroke or peripheral artery occlusion

The drug Cardogrel® is used in a dose of 75 mg once a day.After myocardial infarction, treatment can begin from the first days to the 35th day, with ischemic stroke - in the period from 7 days to 6 months.

In acute coronary syndrome without ST segment elevation (unstable angina or myocardial infarction without Q-wave)

The drug Cardogrel® should be started with a single dose of 300 mg (4 tablets of 75 mg), and then continue 75 mg once a day (in combination with acetylsalicylic acid at a dose of 75-325 mg per day, while it is recommended that the daily dose of acetylsalicylic acid does not exceed 100 mg). The optimal duration of treatment to 12 months, the maximum therapeutic effect is observed after 3 months after the start of therapy.

In acute coronary syndrome with ST segment elevation (acute myocardial infarction with ST segment elevation)

The drug Cardogrel® is used at a dose of 75 mg / day once, starting with a loading dose of 300 mg (4 tablets of 75 mg), in combination with acetylsalicylic acid, as well as with or without thrombolytic therapy. In patients older than 75 years, Cardogrel® should be used without the initial loading dose.After the development of symptoms, it is necessary to start using combination therapy for at least 4 weeks as early as possible.

In patients with a genetically determined decrease in the function of the isoenzyme CYP2C19, a decrease in the effect of clopidogrel may be possible. The optimal dosage regimen in these patients is not established. The effectiveness of combined use of clopidogrel and acetylsalicylic acid for more than 4 weeks with acute coronary syndrome with ST segment elevation (acute myocardial infarction with ST segment elevation) has not been studied.

With atrial fibrillation (atrial fibrillation)

The drug Cardogrel® is used in a dose of 75 m g once daily in combination with acetylsalicylic acid at a dose of 75-100 mg per 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 activity of the isoenzyme 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 daily) in patients with a low activity of the isoenzyme CYP2C19 increases the antiplatelet effect of clopidogrel (see section "Pharmacokinetics"). However, at the present time in clinical studies that take into account clinical outcomes, the optimal dosage regimen of clopidogrel has not been established for patients with its reduced metabolism due to the genetically caused low activity of the CYP2C19 isoenzyme.

Special patient groups

Elderly patients

In elderly volunteers (over 75 years old), when compared with young volunteers, there was no difference in platelet aggregation and bleeding time. Do not require dose adjustment for elderly patients.

Children

There is no experience of using the drug in children.

Patients with impaired renal function

After repeated use of clopidogrel at a dose of 75 mcg ducks in patients with severe renal disease (creatinine clearance 5 to 15 ml / min), inhibition of ADP-induced platelet aggregation (25%) was lower compared to that in healthy However, the prolongation of bleeding time was similar to that of healthy volunteers who received clopidogrel in a dose of 75 mg per day. In addition, all patients had good tolerability of the drug.

Patients with impaired hepatic function

After a daily intake of clopidogrel for 10 days at a daily dose of 75 mg in patients with severe liver damage, inhibition of ADP-induced platelet aggregation was similar to that of healthy volunteers. The average bleeding time is also comparable in both groups.

Patients of different ethnicity

The prevalence of the alleles of the CYP2C19 isoenzyme genes responsible for the intermediate and decreased metabolism of clopidogrel to its active metabolite differs among representatives of different ethnic groups (see section "Pharmacogenetics"). There are only limited data for representatives of the Mongoloid race on the impact of the genotype of the isoenzyme CYP2C19 on clinical outcome events.

Female and male patients

In a small study comparing the pharmacodynamic properties of clopidogrel in males and females, there was less inhibition of ADP-induced platelet aggregation in women, but there was no difference in lengthening the bleeding time.In the study of clopidogrel in comparison with acetylsalicylic acid in patients with the risk of developing ischemic complications, the frequency of clinical outcomes, other side effects and deviations from the norm of clinical and laboratory indicators was the same for both men and women.

Side effects:

According to the World Health Organization (WHO), undesirable effects are classified according to their frequency of development as follows: very often (≥ 1/10), often (≥1/100, <1/10), infrequently (≥1/1000, <1/100), rarely (≥1/10000, <1/1000), very rarely (<1/10000), the frequency is unknown (the frequency of occurrence of phenomena can not be determined on the basis of available data).

Violations of the blood and lymphatic system

infrequently: thrombocytopenia, leukopenia, eosinophilia;

rarely: neutropenia, including severe neutropenia;

very rarely: thrombotic thrombocytopenic purpura (see section "Special instructions"), aplastic anemia, pancytopenia, agranulocytosis, severe thrombocytopenia, granulocytopenia, anemia, acquired hemophilia A.

Immune system disorders

very rarely: serum sickness, anaphylactoid reactions, cross allergic or hematological reactions hypersensitivity to drugs of the thienopyridine group (ticlopidine, prasugrel) (see section "Special instructions").

Disorders of the psyche

very rarely: hallucinations, confusion of consciousness.

Disturbances from the nervous system

infrequently: intracranial hemorrhage (several reported fatal cases), headache, paresthesia, dizziness;

very rarely: a violation of taste perception.

Disturbances on the part of the organ of sight

infrequently: ocular hemorrhage (conjunctival, in the tissue and retina of the eye).

Hearing disorders and labyrinthine disorders

rarely: vertigo.

Vascular disorders

often: hematoma; very rarely: serious bleeding, bleeding from the operating wound, vasculitis, lowering of arterial pressure.

Disturbances from the respiratory system, chest and mediastinal organs

often: epistaxis; very rarely: bleeding from respiratory tract (hemoptysis, pulmonary hemorrhage), bronchospasm, interstitial pneumonia, eosinophilic pneumonia.

Disorders from the gastrointestinal tract

often: gastrointestinal bleeding, diarrhea, abdominal pain, dyspepsia;

infrequently: a stomach ulcer and duodenal ulcers, gastritis, Vomiting, nausea, constipation, bloating abdomen;

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 hepatic insufficiency, hepatitis, deviation from the norm of indicators of liver function.

Disturbances from the skin and subcutaneous tissues

often: subcutaneous bruising;

infrequently: rash, itching, purpura (subcutaneous hemorrhage);

very rarely: bullous dermatitis (toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme), angioedema, drug hypersensitivity syndrome, drug rash with eosinophilia and systemic manifestations (DRESS), erythematous or exfoliative rash, urticaria, eczema, flat lichen.

Disturbances from musculoskeletal and connective tissue

very rarely: hemorrhages in the muscles and joints, arthritis, arthralgia, myalgia.

Disorders from the nights and urinary tract ways

infrequently: hematuria;

very rarely: glomerulonephritis, an increase in the concentration of creatinine in the blood.

General disorders and disorders at the site of administration

often: bleeding from a place vascular puncture;

very rarely: fever.

Laboratory and instrumental data

infrequently: increase in time bleeding, reduction the number of neutrophils, decrease in the number of platelets in the peripheral blood.

Overdose:

Symptoms: prolongation of bleeding time and development of subsequent complications associated with bleeding.

Treatment: there is no specific antidote. Symptomatic therapy. Stop bleeding. Transfusion of platelet mass.

Interaction:

Oral anticoagulants: although taking clopidogrel 75 mg / day did not alter the pharmacokinetics of warfarin (substrate of the isoenzyme CYP2C9) or INR (international normalized ratio) in patients receiving long-term treatment with warfarin, concurrent administration of clopidogrel increases the risk of bleeding due to its independent additional effect on blood coagulation.Therefore, care should be taken while taking warfarin and clopidogrel. Simultaneous use of clopidogrel and oral anticoagulants may increase the intensity of bleeding, and therefore the use of this combination is not recommended.

Application inhibitors glycoprotein IIb / IIIa together with clopidogrel increases the risk of bleeding, so this combination requires caution.

Acetylsalicylic acid (ASA) does not alter the inhibitory effect of clopidogrel on ADP-induced platelet aggregation, but clopidogrel potentiates the effect of ASA on collagen-induced platelet aggregation. Nevertheless, simultaneous with clopidogrel administration of ASA 500 mg twice a day for one day did not cause a significant increase in bleeding time caused by the use of clopidogrel. Between clopidogrel and ASA, pharmacodynamic interaction is possible, which leads to an increased risk of bleeding. Therefore, when they are used simultaneously, care must be taken.

Heparin: according to a clinical study conducted with the participation of healthy volunteers, when taking clopidogrel did not require a change in the dose of heparin and did not change its anticoagulant effect.The simultaneous use of heparin did not alter the antiplatelet effect of clopidogrel. 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 evaluated in patients with acute myocardial infarction. The incidence of clinically significant bleeding was similar to that observed with thrombolytic drugs and heparin with ASA.

Non-steroidal anti-inflammatory drugs (NSAIDs): in a clinical study conducted with the participation of healthy volunteers, the combined use of clopidogrel and naproxen increased latent blood loss through the gastrointestinal tract. 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 gastrointestinal bleeding when taking clopidogrel together with other NSAIDs.Therefore, the use of NSAIDs, including COX-2 inhibitors, in combination with clopidogrel, should be performed with caution.

Reception selective serotonin reuptake inhibitors (SSRIs) it interferes with platelet activation and may increase the risk of bleeding, so caution should be exercised when using SSRIs and clopidogrel simultaneously.

Inhibitors of the isoenzyme CYP2CI9: as clopidogrel metabolized to the formation of its active metabolite in part by means of the CYP2C19 system, the use of drugs inhibiting this system can lead to a decrease in the level of the active metabolite of clopidogrel. The clinical significance of this interaction is not established.

It should avoid the simultaneous use with clopidogrel strong or moderate inhibitors of the isoenzyme CYP2C19.

The drugs inhibiting the isoenzyme CYP2CI9 include the following: omeprazole, esomeprazole, fluvoxamine, fluoxetine, moclobemide, voriconazole, fluconazole, ticlopidine, ciprofloxacin, cimetidine, carbamazepine, oxcarbazepine, chloramphenicol. If proton pump inhibitors are to be taken concomitantly with clopidogrel, a proton pump inhibitor with the least inhibition of the CYP2C19 isoenzyme, such as pantoprazole or lansoprazole.

Phenytoin and tolbutamide can be safely applied simultaneously with clopidogrel.

When using clopidogrel together with atenolol, nifedipine or with both drugs simultaneously clinically significant pharmacodynamic interaction was not observed.

Simultaneous application phenobarbital, cimetidine and estrogens had no significant effect on the pharmacodynamics of clopidogrel.

Pharmacokinetic parameters digoxin and theophylline did not change when they were used together with clopidogrel.

Antacid agents did not affect the degree of absorption of clopidogrel.

Patients who participated in clinical trials of clopidogrel received various concomitant medications, including diuretics, beta adrenoblockers, angiotensin converting enzyme (ACE) inhibitors, calcium channel blockers, lipid-lowering drugs, coronary vasodilators, hypoglycemic agents (including insulin), antiepileptic drugs, preparations for hormone replacement therapy.

Special instructions:

Before starting treatment with clopidogrel and then during the treatment period, it is necessary to monitorindicators of the hemostasis system (activated partial thromboplastin time (APTT), platelet count, functional platelet function tests); regularly investigate the functional activity of the liver.

It was reported that cases of development of acquired hemophilia against the background of taking clopidogrel. In the case of a confirmed isolated increase in APTT in combination with or without bleeding, the probability of developing acquired hemophilia should be considered. Patients with a confirmed diagnosis of acquired hemophilia showed supervision and treatment under the supervision of a specialist, taking clopidogrel should be discontinued. It has been shown that in patients with recent transient cerebral infarction or stroke having a high risk of developing recurrent ischemic complications, the combination of ASA and clopidogrel increases the incidence of major bleeding. Therefore, such combination therapy should be conducted with caution and only in the case of proven clinical benefit from its use.

It is necessary to carefully monitor patients for the exclusion of signs of bleeding, including hidden during the use of clopidogrel,especially during the first weeks of treatment and / or after invasive cardiac procedures or surgery.

In the case of surgical interventions, if antiaggregant effect is undesirable, the course of treatment with clopidogrel should be discontinued 7 days before the operation. Patients should be warned that, because of the use of Cardogrel® (in combination with or without ASA), the stopping of bleeding that occurs is more time-consuming, they must inform the doctor of every unusual bleeding event (localization or duration).

Patients should also inform the doctor about taking the medication if they are undergoing surgery (including dental surgery) or if the doctor prescribes a new medication for the patient.

The drug Cardogrel® increases bleeding time, so it should be used with caution in patients with a risk of bleeding (especially gastrointestinal and intraocular).

There were reports of cross-allergic and hematological reactions in the thienopyridine group, caution should be exercised when taking clopidogrel in patients with a hypersensitivity reaction to thienopyridine (clopidogrel, ticlopidine, prasugrel) in the anamnesis.

Tienopyridines can cause allergic or hematological reactions of moderate and severe severity (rash, angioedema, thrombocytopenia, neutropenia). In patients with previously identified allergic or hematologic reactions to one of the drugs from the group of thienopyridines, the same or similar undesirable reactions to another drug from the group of thienopyridines may occur. Such patients are carefully monitored to identify signs of hypersensitivity to the drug.

During the treatment it is necessary to monitor the function of the liver. In case of severe violations of liver function, one should remember about the risk of hemorrhagic diathesis. It is not recommended to take patients with ischemic stroke less than 7 days old.

Very rarely, when taking clopidogrel, thrombotic thrombocytopenic purpura (TTP) developed, sometimes even after short-term use. TTP is a potentially life-threatening condition characterized by thrombocytopenia and microangiopathic hemolytic anemia, accompanied by neurological disorders, renal dysfunction and fever, requiring immediate treatment, including plasmapheresis.

Special precautions for the destruction of unused medicinal product

There is no need for special precautions when destroying an unused preparation of Cardogrel®.

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

The drug Cardogrel® does not significantly affect the management of vehicles and the employment of other potentially hazardous activities requiring increased concentration and speed of psychomotor reactions.

Form release / dosage:

Tablets coated with a film coating, 75 mg.

Packaging:

For 7, 10 or 14 tablets are placed in Al/Al blister or Aclar blister.

For 2, 4, 8 or 12 blisters, 7 tablets are placed in a cardboard box together with instructions for medical use.

For 3 or 9 blisters, 10 tablets are placed in a cardboard box together with instructions for medical use.

For 1, 2 or 3 blisters of 14 tablets are placed in a cardboard box together with instructions for medical use.

Storage conditions:

Store at a temperature not exceeding 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

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

Terms of leave from pharmacies:On prescription

Registration number:LP-002033

Date of registration:22.03.2013

The owner of the registration certificate:Sandoz d.Sandoz d. Slovenia

Manufacturer: & nbsp

SANDOZ, d.d. Slovenia

Representation: & nbspSANDOZ SANDOZ Switzerland

Information update date: & nbsp06.08.2015

Illustrated instructions

Instructions

Cardogrel® (Cardogrel®)