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

Excipients: lactose anhydrous 48.94 mg, methylcellulose 15 CCPS 17.0 mg, crospovidone 12.0 mg, silicon dioxide colloid 0.40 mg, zinc stearate 3.80 mg;

film coating: giprolase LF 1.20 mg, hypromellose 2910 E5 0.40 mg, macrogol-8000 0.80 mg, titanium dioxide (E 171) 1.00 mg, ferric iron oxide red (E 172) 0.20 mg.

Description:

Round, biconvex tablets covered with a film coat of a reddish-brown color. On one side is engraved "ARO", on the other side - "C1" above "75".

With a transverse fault, the core is white or almost white, surrounded by a shell of reddish-brown color.

Pharmacotherapeutic group:Antiaggregant agent

ATX: & nbsp

B.01.A. C.04 Clopidogrel

Pharmacodynamics:

Antiaggregant agent. Selectively reduces the binding of adenosine diphosphate (ADP) to receptors on platelets and activation of receptors of glycoprotein IIb/IIIa under the action of ADP, thereby violating the aggregation of platelets.

Reduces platelet aggregation, caused by other agonists, preventing their activation by released ADP; does not affect the activity of phosphodiesterase (PDE). Irreversibly binds to ADP-receptor platelets, which remain immune to stimulation of ADP throughout the life cycle (about 7 days). The inhibition of platelet aggregation is observed after 2 hours after administration (40% inhibition) of the initial dose of 400 mg.The maximum effect (60% suppression of aggregation) develops after 4-7 days of constant admission in a dose of 50-100 mg / day. Antiaggregant effect persists throughout the life span of platelets (7-10 days).

Pharmacokinetics:

Absorption and bioavailability - high; the concentration of clopidogrel in the plasma is low and after 2 hours after taking it does not reach the measurement limit (0.025 μg / l). The connection with plasma proteins is 98-94%. Is a prodrug. Metabolised in the liver. An active metabolite is not found in the blood. The main detectable metabolite is the inactive derivative of carboxylic acid, the time to reach the maximum concentration (T_Сmах) which after repeated oral doses of 75 mg is achieved after 1 hour (maximum concentration C_max - about 3 mg / l).

Excretion: by kidneys - 50%, through the intestine - 46% (within 120 hours after administration). The half-life (T_1/2) of the main metabolite after a single and repeated intake - 8 hours. Concentrations of kidney metabolites - 50%.

The concentration of the main metabolite in plasma after taking 75 mg / day is lower in patients with severe chronic renal failure (creatinine clearance 5-15 ml / min) compared with chronic renal failure of moderate severity (creatinine clearance 30-60 ml / min) and healthy individuals .

Indications:

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

Prophylaxis of thrombotic complications (in combination with acetylsalicylic acid) in acute coronary syndrome:

- without lifting the segment ST (unstable angina, myocardial infarction without a tooth Q), including patients undergoing stenting;

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

Contraindications:

- Hypersensitivity to clopidogrel or any of the excipients of the drug;

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

severe hepatic impairment;

- Acute pathological bleeding (including bleeding from the peptic ulcer or intracranial hemorrhage);

- pregnancy and lactation;

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

Carefully:

When:

- moderate degree of hepatic insufficiency, chronic renal failure (CRF);

- pathological conditions that increase the risk of bleeding (including trauma, surgery), the tendency to bleeding;

- simultaneous administration of acetylsalicylic acid, warfarin, non-steroidal anti-inflammatory drugs (including COX-2 inhibitors), heparin and inhibitors of glycoprotein Ilb / IIIa;

- a hereditary decrease in the function of the isoenzyme CYP2C19.

Pregnancy and lactation:

In the absence of data, it is not recommended to take clopidogrel during pregnancy and during breastfeeding.

Dosing and Administration:

Inside, regardless of food intake.

For the prevention of thrombotic complications in patients with myocardial infarction, ischemic stroke or peripheral arterial occlusion - 75 mg once a day.

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

For prophylaxis of thrombotic complications in acute coronary syndrome without segment elevation ST (unstable angina, myocardial infarction without a tooth Q) - begin with a single dose of loading dose - 300 mg,and then take 75 mg / day (in combination with acetylsalicylic acid in doses of 75-325 mg / day, the recommended dose is 100 mg / day). The maximum favorable effect occurs after 3 months. The course of treatment is up to 1 year.

For the prevention of thrombotic complications in acute coronary syndrome with segment elevation ST (acute myocardial infarction with segment elevation ST) - 75 mg / day with the initial single dose loading in combination with acetylsalicylic acid and thrombolytic agents (or without thrombolytics).

Combination therapy is started as soon as possible after the onset of symptoms and continues for at least 4 weeks. In patients older than 75 years, treatment with clopidogrel should begin without taking its loading dose.

In patients with a genetically determined decrease in the isoenzyme function CYP2C19 possibly reducing the effect of clopidogrel. The optimal dosage regimen in these patients is not established.

The experience of using in patients with chronic renal or moderate degree of liver failure is limited.

Side effects:

Frequency: very often - more than 1/10, often - more than 1/100 and less than 1/10, infrequently - more than 1/1000 and less than 1/100, rarely - more than 1/10000 and less than 1/1000, very rarely - less than 1/10000, including isolated cases.

On the part of the organs of hematopoiesis: infrequently - thrombocytopenia, leukopenia, eosinophilia; rarely - neutropenia, incl. expressed; very rarely - thrombotic thrombocytopenic purpura, anemia, incl. aplastic, pancytopenia, agranulocytosis, severe thrombocytopenia, granulocytopenia.

Allergic reactions: very rarely - anaphylactic reactions, serum sickness.

From the nervous system: infrequently - headache, dizziness, paresthesia, intracranial hemorrhage, incl. with lethal outcome; very rarely - confusion, hallucinations, a taste disorder.

From the sense organs: infrequently - hemorrhage in the conjunctiva, eyes, retina; rarely - vertigo.

From the side of the cardiovascular system: often - hematoma; very rarely - heavy bleeding, bleeding from the operating wound, vasculitis, lowering blood pressure.

From the respiratory system: very often - nosebleeds; very rarely - bronchospasm, interstitial pneumonitis, pulmonary hemorrhage, hemoptysis.

From the digestive system: often - diarrhea, abdominal pain, indigestion, bleeding from the gastrointestinal tract; infrequently - stomach ulcer and duodenal ulcer, gastritis, vomiting, nausea, constipation, flatulence; rarely - retroperitoneal bleeding; very rarely - pancreatitis, colitis, incl.ulcerative or lymphocytic, stomatitis, acute hepatic insufficiency, hepatitis, a violation of functional liver tests, bleeding from the gastrointestinal tract with a lethal outcome.

From the skin: often - subcutaneous hemorrhage; infrequently - skin rash, itching, purpura; very rarely - angioedema, urticaria, erythematous rash, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, eczema, lichen planus.

From the side of the musculoskeletal system: very rarely - hemarthrosis, arthritis, arthralgia, myalgia.

From the genitourinary system: infrequently - hematuria; very rarely - glomerulonephritis, hypercreatininaemia.

Local Reactions: often - bleeding at the injection site.

Laboratory indicators: infrequent - prolongation of bleeding time.

Other: very rarely - fever.

Overdose:

Symptoms

An overdose of clopidogrel may lead to an increase in bleeding time and hemorrhagic complications.

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:

Simultaneous reception warfarin with clopidogrel may increase the intensity of bleeding, so the use of this combination is not recommended.

Appointment inhibitors of glycoprotein IIb / IIIa, acetylsalicylic acid, heparin together with clopidogrel increases the risk of bleeding.

Non-steroidal anti-inflammatory drugs (NSAIDs): with simultaneous use may increase the risk of bleeding.

Simultaneous reception with inhibitors of CYP2C19 (eg, omeprazole) Not recommended.

The active metabolite of clopidogrel inhibits the activity of the isoenzyme CYP2C9, resulting in increased concentrations of phenytoin, tolbutamide and NSAIDs in plasma.

Special instructions:

In the case of surgical interventions, if antiaggregant effect is undesirable, the course of treatment should be discontinued 7 days before the operation.

Patients should be warned that because the stoppage of the bleeding that occurs when the drug is used requires more time, they should inform the doctor about every case of unusual bleeding.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.

During the treatment period, it is necessary to monitor the parameters of the hemostasis system (activated partial thromboplastin time, platelet count, platelet functional activity tests); regularly investigate the functional activity 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 prescribe to patients with ischemic stroke less than 7 days old.

Very rarely, when taking clopidogrel, thrombotic thrombocytopenic purpura developed, sometimes after short-term use. The condition is characterized by thrombocytopenia and microangiopathic hemolytic anemia, associated with neurologic disorders, kidney damage and fever. Thrombotic thrombocytopenic purpura is a potentially life threatening condition requiring immediate treatment, including plasmapheresis.

Clopidogrel should not be taken to patients with rare hereditary intolerance lactose (see FIG."Composition").

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

Clopidogrel can cause side effects from the nervous system, which can affect the ability to drive vehicles, mechanisms and to engage in other potentially dangerous activities that require increased concentration and speed of psychomotor reactions.

Form release / dosage:

Tablets coated with a film coating, 75 mg.

Packaging:

At packing and packing at the Russian enterprise of Joint-Stock Company "VECTOR-MEDICA": on 14, 20 or 28 tablets in bottles of high-density polyethylene, ukuporennye lid from the bottle material. 1 bottle with instructions for use put in a pack of cardboard.

10 tablets per contour cell packaging made of polyvinylchloride film and aluminum foil. For 1, 2 or 3 contour squares, together with the instructions for use, are placed in a pack of cardboard.

For hospitals: 100 tablets per bottle of high-density polyethylene, Capped with a lid from the bottle. Bottles (from 20 to 90 bottles), along with instructions for use, are placed in a cardboard box. The number of instructions should correspond to the number of bottles.

Storage conditions:

Store in a dry protected from light, at a temperature of 15 to 30 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

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

Terms of leave from pharmacies:On prescription

Registration number:PL-000575

Date of registration:26.08.2011

Expiration Date:26.08.2016

The owner of the registration certificate:Apothec Inc.Apothec Inc. Canada

Manufacturer: & nbsp

APOTEX, Inc. Canada

Representation: & nbspTORRENT PHARMACEUTICALS LTD. TORRENT PHARMACEUTICALS LTD. India

Information update date: & nbsp12.12.2017

Illustrated instructions

Instructions

Cardutol® (Kardutol®)