Zilt

Zilt is an antithrombotic drug, is part of a group of antiplatelet agents.

Indications of the zilta

It is used to prevent the appearance of atherothrombotic symptoms in persons:

• suffered a seizure of myocardial infarction (to start therapy is required in the period from several days to 35 days after its development);
• who suffered a stroke of an ischemic type (starting the course is required in the period of 7 days, but not later than six months after its development);
• who were diagnosed with pathology in the peripheral arteries (arterial lesions, as well as vascular atherothrombosis in the legs).

For prevention also for people with ACS:

• without increasing the level of the ST segment (with the development of unstable angina or myocardial infarction without the presence of a Q-type tooth). This category also includes individuals who during the transcutaneous angioplasty of the coronary type a stent was inserted; together with aspirin;
• in acute form of myocardial infarction, when there is an increase in the level of the ST segment - together with aspirin; people who receive therapy with standard drugs, and who require thrombolytic treatment.

The drug is also used for prophylaxis in thromboembolic as well as atherothrombotic manifestations during atrial fibrillation.

For the above purpose, clopidogrel in combination with aspirin is prescribed to persons with atrial fibrillation who have at least 1 risk factor for the occurrence of vascular disorders. In addition, such people have contraindications to the use of antagonists of phylloquinone, and together with this they have a low probability of bleeding.

Release form

Release in tablets, 7 pieces inside the blister cell. Inside a separate bundle there are 4 such blisters.

Pharmacodynamics

The substance clopidogrel selectively inhibits the synthesis of ADP with a platelet-based receptor, as well as the subsequent activation of a GP IIb / IIIa complex (as a result of ADP), thereby inhibiting the possibility of platelet aggregation.

To obtain an active inhibitor of the platelet aggregation process, biotransformation of clopidogrel is required. This component inhibits and platelet aggregation, which is caused by other agonists - blocking the increase in platelet activity under the action of the released element ADP. An irreversible binding of the active drug component to platelet ADP receptors is carried out. As a result, those platelets that have been exposed to clopidogrel are damaged before the end of their life cycle. In this case, the restoration of normal platelet function occurs at a rate similar to the rate at which the platelets are updated.

From the 1st day of drug use in repeated daily doses (75 mg), significant inhibition of ADP-induced platelet aggregation occurs. This effect progressively increases, and then stabilizes during the 3-7th day. In the equilibrium state, the average suppression of the aggregation process under the influence of a daily dose of 75 mg is in the range of 40-60%. Bleeding time, as well as platelet aggregation, return to their initial values after 5 days (on average) after the end of therapy.

Pharmacokinetics

As a result of repeated oral administration of Zilt in a daily dosage of 75 mg, rapid absorption of clopidogrel occurs. The peak of the plasma values of the unchanged substance (approximately 2.2-2.5 ng / ml when ingested by a single dose of 75 mg) reached approximately 45 minutes after ingestion. The suction index is at least 50%, judging by the level of the decay products of the drug excreted in the urine.

Clopidogrel together with the inactive major decay product circulate inside the bloodstream. They are reversibly synthesized (in vitro) with a plasma protein - 98% and 94%, respectively. This bond is preserved unsaturated during in vitro action within the limits of a wide range of different concentrations.

Clopidogrel undergoes extensive liver metabolism. In in vitro and in vivo processes, there are 2 main metabolic pathways of the substance: in one of them, the process occurs with the help of esterases and causes hydrolysis, which results in the formation of an inactive derivative of the carboxylic acid (it accounts for 85% of all the decomposition products circulating inside the plasma). The second way is action with the participation of enzymes of the hemoprotein system P450. Initially, clopidogrel is converted into a decay product of the intermediate type: 2-oxo-clopidogrel. While continuing to be metabolized, this element turns into a thiol derivative, which is an active product of decay. In in vitro processes, this pathway is mediated by CYP3A4 enzymes with CYP2C19, as well as CYP1A2 with CYP2B6. Isolated in vitro thiol derivative is irreversibly and quickly synthesized with platelet-based receptors, not permitting aggregation with them.

After oral administration of a single dose of Zilt (75 mg), the half-life of the active ingredient is about 6 hours. The main circulating decay product has an 8-hour half-life (with a single or repeated dose).

If you use a dose of drugs with a 14C indicator inside, approximately 50% of the substance is excreted together with urine, and about 46% - with feces in the 120 hours after application.

[1]

Dosing and administration

Clopidogrel is taken once a day at a dosage of 75 mg, regardless of eating.

For people with ACS:

• In the absence of an increase in the ST segment, therapy begins with a one-time loading dose of 300 mg, and after it continues to be taken 75 mg once a day (in combination with aspirin in the amount of 75-325 mg per day). Since the use of aspirin in stronger doses increases the likelihood of bleeding, do not exceed the 100 mg mark when dosing. There is no information about the optimal duration of therapy. The results of clinical tests suggest that the most appropriate is a scheme with a course lasting no more than 1 year. At the same time, the maximum effect of drugs is observed after 3 months of treatment;
• people with a sharp attack of myocardial infarction, at which there is an increase in the ST segment: it is necessary to take the drug 75 mg once a day, starting with a loading dose of 300 mg, in combination with or without aspirin and thrombolytics. In this case, people over 75 years of age should be treated without the use of a loading dose. Complex treatment is required to begin as quickly as possible after the appearance of signs of violation, and continue at least during the first month. In this category of patients, the benefits of using Zilt in combination with aspirin for more than 4 weeks have not been studied.

People with atrial fibrillation need to drink a medicine in the amount of 75 mg once a day. Along with the drug, aspirin is also used (in a daily dosage of 75-100 mg).

If a dose was missed:

• in the case when less than 12 hours have passed since the time at which the medication is usually taken, the missed dosage should be used immediately, and the subsequent dose should be taken at standard time;
• after a period of more than 12 hours, the patient is required to take the next tablet in the standard time. Doubling the dosage taken to compensate for the missed dose is prohibited.

[3]

Use of the zilta during pregnancy

Since there is no information on the effects of clopidogrel on pregnant women, it is forbidden to use the medication at this time.

There is also no information about the passage of clopidogrel in the mother's milk, so that during the use of the medicine, you must refrain from breastfeeding.

The negative impact of Zilt on the level of fertility of laboratory animals was not revealed.

Contraindications

Among the contraindications:

• hypersensitivity to the active component of drugs or other of its auxiliary elements;
• a disorder in the liver in a severe degree;
• acute form of bleeding (eg, hemorrhage inside the skull or ulcer);
• there is no information about the use of the drug in children or adolescence.

Side effects of the zilta

The use of a medicine can trigger the appearance of certain side effects:

• disorders of lymphatic function and systemic blood flow: development of leuko-, neutron (including in severe form), granulocyte, pancy- or thrombocytopenia (also severe), and also eosinophilia. In addition, there may be TTP, anemia (both normal and aplastic form), agranulocytosis, as well as hemophilia of acquired character;
• immune manifestations: the development of serum sickness, as well as anaphylactoid symptoms. Cross-intolerance may also develop between thienopyridine (eg, prasugrel or ticlopidine);
• mental disorders: a sense of confusion, as well as the appearance of hallucinations;
• reactions of the organs of the NS: bleeding inside the skull (sometimes leading to death), paresthesia, dizziness, a disorder of taste buds and headaches;
• problems with visual organs: bleeding in the eye (in the conjunctiva, as well as retinal or ocular bleeding);
• manifestations in the vascular system: severe hemorrhage, the appearance of vasculitis, hematomas, bleeding from a surgical wound, and a decrease in blood pressure;
• disorders in the respiratory system, the sternum, and mediastinum: bleeding from the nose, as well as hemorrhages in the respiratory duct (bleeding in the lungs, and in addition hemoptysis), bronchial spasms, fibrosing alveolitis and pneumonia of the eosinophilic type;
• manifestations in the gastrointestinal tract: bleeding in this area, abdominal pain, diarrhea, dyspeptic manifestations, gastritis, bloating, as well as vomiting and ulcer pathology in the stomach or 12-gut. In addition, nausea, retroperitoneal hemorrhage, bleeding in the gastrointestinal tract and retroperitoneal type (with fatal outcome), as well as stomatitis and pancreatitis with colitis (this includes its lymphocytic or ulcerative form);
• manifestations of GVP and liver: acute disorder of hepatic functions, hepatitis, as well as an abnormal level of functional hepatic indicators;
• manifestations in the area of the subcutaneous layer and skin: rashes, hemorrhage under the skin, itching, purpura, as well as dermatitis bullous type (TEN, polyiform erythema and Stevens-Johnson syndrome). In addition, Quincke edema develops, erythematous rash, urticaria, drug intolerance syndrome, drug-induced rash accompanied by eosinophilia, and general symptoms (the so-called DRESS syndrome), and also flat lichen or eczema;
• connective tissue and structure of bones with muscles: the development of myalgia, hemarthrosis, arthralgia or arthritis;
• disturbances in the work of the urinary system and kidneys: development of glomerulonephritis or hematuria, as well as an increase in creatinine;
• systemic disorders: fever;
• change in indications of instrumental and laboratory tests: decrease in the number of platelets with neutrophils, as well as prolongation of bleeding time.

[2]

Overdose

As a result of an overdose, an extension of the bleeding period may occur with further development of complications.

Treatment is aimed at eliminating manifestations of the disorder. The medicine does not have an antidote. If immediate correction of the prolonged bleeding time is required, it is possible to get rid of the influence of drugs with the help of transfusion of platelet mass.

Interactions with other drugs

Ingestable anticoagulants.

Combination with these medicines is not recommended, because such a combination can provoke an increase in the intensity of bleeding. Although the use of clopidogrel in a daily dosage of 75 mg does not affect the pharmacokinetics of S-warfarin or the INR rate in people who have long been treated with warfarin, the combined use of these agents increases the likelihood of bleeding due to the independent effect on the process of hemostasis.

Medications that slow down the activity of glycoprotein IIb / IIIa.

Care should be taken to prescribe clopidogrel to people who are more likely to have bleeding due to surgery, trauma or other disorders, together with glycoprotein IIb / IIIa inhibiting agents.

Aspirin.

Aspirin does not affect ADP-induced platelet aggregation due to the use of clopidogrel, but clopidogrel potentiates the effects of aspirin on the platelet aggregation caused by collagen. Although the combined use of 500 mg of aspirin twice per day during the first day did not cause a significant increase in the bleeding time, which is increased due to the use of clopidogrel. Because aspirin and clopidogrel may interact, increasing the likelihood of bleeding, the combined use of these drugs should be cautious. But there is evidence of a parallel reception of Zilt with aspirin in the period up to 12 months.

Heparin.

Since drug interaction with heparin increases the likelihood of bleeding, these medication should be carefully combined.

Thrombolytic drugs.

Evaluation of the safety of the combined use of clopidogrel, as well as heparin and thrombolytic fibrin-specific or fibrin-nonspecific type, occurred with the participation of people with acute myocardial infarction. The frequency of drug-significant bleeding was similar to that observed during concomitant use of thrombolytic drugs, as well as aspirin with heparin.

NSAIDs.

Combination of the drug with naproxen increases the number of hidden bleeding inside the gastrointestinal tract. But it has not yet been possible to ascertain whether the likelihood of bleeding in the digestive tract increases with any NSAID. Because of this, it is required to combine with the preparation with NSAID with caution (this includes also inhibitors of the element COX-2).

Combination with other medicines.

Since clopidogrel is transformed into its active degradation product, and partly by the action of the element CYP2C19, the use of drugs that decrease the activity of this enzyme is likely to lower the plasma metabolite values. To prevent such an effect, it is necessary to avoid combined administration of the drug with potent or moderate inhibitors of the element CYP2C19.

Among the drugs that reduce the effectiveness of CYP2C19 - esomeprazole, voriconazole with omeprazole, fluoxetine, fluconazole with fluvoxamine, and in addition ticlopidine with moclobemide, cimetidine with chloramphenicol, ciprofloxacin and oxcarbazepine with carbamazepine.

Medicines IPP.

A single dose of 80 mg for omeprazole per day, in combination with clopidogrel or with the use of these medicines in a period of no more than 12 hours, the level of the active degradation product decreased by 45% (with a loading dose), and 40% (at a dose supporting type). Against the backdrop of such a decrease, platelet aggregation inhibition also decreased, by 39% (with the loading type of dosing), and by 21% (with a maintenance type of dosing). It can be expected that similar interaction with the drug will be with esomeprazole. Therefore, it is not recommended to take the above medicines in combination.

A less noticeable decrease in the level of the metabolite inside the blood was noted in the case of a combination with lansoprazole or pantoprazole. Use in combination Zilt and pantoprazole - it is quite possible.

Combination therapy with other medications.

Antacids do not affect the degree of absorption of clopidogrel. Carboxylic decomposition products of the substance can inhibit the activity of hemoprotein P450 2C9. As a result, the plasma value of the following drugs - tolbutamide, phenytoin, and also NSAIDs metabolized with the help of hemoprotein P450 2C9 may increase. Tolbutamide with phenytoin is allowed to combine with clopidogrel.

[4], [5], [6], [7], [8]

Storage conditions

The Zilt must be kept in a place that is closed from penetration of moisture and sunlight, and also inaccessible to small children.

[9], [10]

Special instructions

Reviews

Zilt is considered a very effective medication. Its worth is also considered a fairly low price (in comparison with other analogs). The reviews show that the drug is highly effective in case of application after stent placement, as well as the transfer of a heart attack. Improvement of health status, disappearance of stenocardia attacks and thrombosis in the field of veins with arteries are noted.

Of the disadvantages - individual patients talk about the development of side effects (such as strong dyspnea and urticaria). But with the continuation of the course of therapy, these negative manifestations disappear on their own after a short period of time.

[11], [12]

Shelf life

Zilt can be used in the period of 3 years from the date of manufacture of the drug.