Tromborel
Tromborel: instructions for use and reviews
- 1. Release form and composition
- 2. Pharmacological properties
- 3. Indications for use
- 4. Contraindications
- 5. Method of application and dosage
- 6. Side effects
- 7. Overdose
- 8. Special instructions
- 9. Application during pregnancy and lactation
- 10. Use in childhood
- 11. In case of impaired renal function
- 12. For violations of liver function
- 13. Use in the elderly
- 14. Drug interactions
- 15. Analogs
- 16. Terms and conditions of storage
- 17. Terms of dispensing from pharmacies
- 18. Reviews
- 19. Price in pharmacies
Latin name: Tromborel
ATX code: B01AC04
Active ingredient: clopidogrel (Clopidogrel)
Producer: Edge Pharma Private Limited (India)
Description and photo update: 2020-25-02
Tromborel is an antiplatelet agent.
Release form and composition
Dosage form - film-coated tablets: round, from light pink to pink; 2 layers stand out on the fracture - a pink shell and a light yellow core (10 and 14 pcs. in blisters, in a cardboard box instructions for the use of Tromborel and 1, 2, 4 or 6 blisters containing 14 tablets each, or 1, 2, 3 or 10 blisters containing 10 tablets).
The composition of the drug for 1 tablet:
- active substance: clopidogrel (in the form of hydrogen sulfate) - 75 mg;
- auxiliary components: calcium stearate, microcrystalline cellulose, mannitol, sodium carboxymethyl starch;
- film sheath: Brown Winkout (ethylcellulose, talc, triacetin, titanium dioxide, hypromellose, iron oxide red).
Pharmacological properties
Pharmacodynamics
The active ingredient of Tromborel, clopidogrel, is a prodrug, since one of its active metabolites is an inhibitor of platelet aggregation.
The active metabolite selectively reduces the binding of adenosine diphosphate (ADP) to receptors on platelets, and also selectively inhibits the activation of the complex of glycoprotein (GP) receptors IIb / IIIa, thereby weakening platelet aggregation.
Clopidogrel has no effect on phosphodiesterase (PDE) activity. It is able to reduce platelet aggregation, which develops under the action of other agonists, by reducing their activation by released ADP.
The drug irreversibly binds to platelet ADP receptors, which remain immune to ADP stimulation during the life cycle (about 7 days).
It is worth noting that satisfactory platelet suppression is not observed in all patients. This is due to the fact that isozymes of the cytochrome P450 system, including polymorphic ones and capable of being inhibited by other drugs, are involved in the formation of the active metabolite of clopidogrel.
In patients with atherosclerotic vascular lesions, Tromborel prevents the development of atherothrombosis, regardless of the vessels where the process is localized (cardiovascular, peripheral or cerebrovascular lesions).
After taking clopidogrel at a dose of 400 mg, the effect develops within 2 hours (inhibition - 40%), the maximum reaches (suppression of aggregation - 60%) - after 4-7 days of regular intake of the drug in a daily dose of 50-100 mg. The antiplatelet effect persists throughout the life of platelets (up to 10 days).
According to the results of a small comparative study of the pharmacodynamics of clopidogrel, which involved men and women, women have less suppression of ADP-induced aggregation, but there is no difference in the lengthening of bleeding time.
The large-scale controlled study Clopidogrel vs Aspirin in Patients at Risk of Ischemic Events (CAPRIE) studied the comparative characteristics of clopidogrel and acetylsalicylic acid (ASA) in patients at risk of developing ischemic pathologies. It was found that the following parameters were similar in women and men: the frequency of clinical outcomes, the number of side effects, the number of other violations of clinical and laboratory parameters.
Pharmacokinetics
With a regular intake of a daily dose of Tromborel 75 mg, clopidogrel is rapidly absorbed. Possesses high bioavailability. However, its plasma concentration is low, already 2 hours after administration, it does not reach the measurement limit, which is 0.025 μg / l. About 98% of clopidogrel and 94% of its inactive metabolite bind to plasma proteins.
The substance undergoes intensive metabolism in the liver. Under in vitro and in vivo conditions, two pathways of biotransformation were observed: the first, with the participation of esterases followed by hydrolysis, as a result of which an inactive derivative of carboxylic acid is formed (85% of the circulating metabolites); the second - under the influence of cytochrome P450 isoenzymes. Initially, clopidogrel is metabolized to an intermediate metabolite - 2-oxoclopidogrel, then to an active metabolite of a thiol derivative of clopidogrel. In vitro, this biotransformation pathway occurs with the participation of isoenzymes CYP1A2, CYP2C19, CYP2B6, CYP3A4, P450. The isoenzyme CYP2C19 is involved in the formation of both 2-oxoclopidogrel and an active metabolite.
Approximately 50% of the drug is excreted by the kidneys, about 46% by the intestines. The elimination time after oral administration is about 120 hours.
The half-life (T 1/2) after a single dose of 75 mg is 6 hours. T 1/2 of the inactive metabolite after a single and multiple doses is 8 hours.
Pharmacokinetic parameters of clopidogrel in special clinical cases:
- Severe kidney damage: after repeated administration of the drug in a daily dose of 75 mg, the initiation of ADP-induced platelet aggregation in patients with creatinine clearance (CC) of 5-15 ml / min was 25% lower than in healthy volunteers who received a similar dose. However, the lengthening of bleeding time was about the same;
- severe liver damage: after regular administration of Tromborel at a daily dose of 75 mg for 10 days, inhibition of ADP-induced platelet aggregation and mean bleeding time in patients with severely impaired liver function were similar to those in healthy volunteers;
- ethnicity: representatives of different ethnic groups differ in the prevalence of alleles of the genes of the isoenzyme CYP2C9, which are responsible for intermediate and reduced metabolism. There are limited literature data on the representatives of the Mongoloid race, but they are insufficient to assess the significance of genotyping of the isoenzyme CYP2C19 in relation to the clinical outcome of events;
- children's age: in children, the pharmacokinetics of the drug has not been studied;
- elderly age: when comparing the indicators in patients over 75 years old and younger healthy volunteers, significant differences were not noted, therefore, dose adjustment of clopidogrel is not required.
Pharmacogenetics
Under ex vivo conditions (experiments on living tissue transferred from the body to an artificial environment) in the study of platelet aggregation, the pharmacological parameters and antiplatelet property of the active metabolite varied depending on the genotype of the CYP2C19 isoenzyme.
The allele of the CYP2C19 * 1 gene fully corresponds to functional metabolism. However, the alleles of the CYP2C19 * 2 and CYP2C19 * 3 genes are non-functional - they are the reason for the decrease in drug metabolism in most representatives of the Mongoloid (99%) and Caucasian (85%) races. In rarer cases, other alleles are found that cause a decrease or absence of metabolism, such as CYP2C19 * 4, * 5, * 6, * 7 and * 8. Poor metabolizers are patients possessing two of these alleles of the loss-of-function gene.
The frequency of phenotypes of patients considered to be weak metabolizers of CYP2C19 is 14% in the Mongoloid race, 4% in the Negroid race, and 2% in the Caucasian race. Special tests have been developed to determine the genotype of the CYP2C19 isoenzyme. With a reduced metabolism of the indicated isoenzyme, a 30-50% decrease in the maximum plasma concentration (Cmax) and the area under the concentration-time curve (AUC) of the active metabolite was noted after taking a loading dose of clopidogrel (300 or 600 mg) followed by a maintenance dose of 75 mg. Due to a decrease in the activity of the metabolite, a decrease in platelet inhibition or an increase in their reactivity is possible.
Indications for use
Tromborel is indicated for the prevention of atherothrombotic disorders in patients diagnosed with occlusive peripheral arterial disease, ischemic stroke 7–180 days old, myocardial infarction not more than 35 days old.
The drug is used in combination with ASA to prevent atherothrombotic episodes in patients with acute coronary syndrome:
- without ST segment elevation: myocardial infarction without Q wave and unstable angina pectoris, including in patients who underwent stenting through percutaneous coronary intervention;
- with ST-segment elevation: acute myocardial infarction, amenable to drug treatment and accompanied by the possibility of thrombolysis.
Contraindications
Absolute:
- active pathological bleeding (for example, intracranial hemorrhage or peptic ulcer);
- severe liver failure;
- period of pregnancy and lactation;
- age up to 18 years;
- hypersensitivity to any component of the drug.
Relative (Tromborel should be taken with caution):
- pathological conditions in which the risk of bleeding increases (for example, surgery or injury);
- chronic renal failure;
- moderate hepatic impairment;
- combined use of ASA, inhibitors of glycoprotein IIb / IIIa, heparin, non-steroidal anti-inflammatory drugs (NSAIDs), including inhibitors of cyclooxygenase-2 (COX-2);
- carriage of alleles of weakened metabolism of CYP2C19 (in patients, the antiplatelet activity of the drug is less pronounced due to the formation of a smaller amount of an active metabolite; in acute coronary syndrome and percutaneous coronary intervention in weak metabolizers receiving clopidogrel in therapeutic doses, the incidence of cardiovascular complications increases).
Tromborel, instructions for use: method and dosage
Tromborel tablets should be taken orally. Meal time does not matter. Adult patients, including the elderly, are prescribed 1 tablet (75 mg) 1 time per day.
After myocardial infarction, treatment should be started within 35 days, after ischemic stroke - from 7 days to 6 months.
Recommended doses of Tromborel:
- acute coronary syndrome without ST-segment elevation: loading dose - 300 mg (4 tablets of 75 mg), further dose - 75 mg 1 time per day in combination with ASA in a daily dose of 75–325 mg (however, it is important not to exceed the dose of ASA 100 mg, since there is a high risk of bleeding);
- acute myocardial infarction with ST segment elevation: loading dose - 300 mg, then - 75 mg 1 time per day in combination with ASA, if necessary, additional thrombolytics are prescribed.
Patients aged 75 and over should use Tromborel at the recommended dose without taking a loading dose. Combination therapy should be started as early as possible after the development of the corresponding symptoms and continued for at least 4 weeks.
For persons with a genetically determined decrease in the function of the isoenzyme CUR2C19, the optimal dose of Tromborel has not been established.
Side effects
- on the part of the vascular system and hematopoietic organs: often (from> 1/100 to 1/1000 to 1/10 000 to <1/1 000) - neutropenia (including severe); very rarely (<1/10 000) - thrombotic thrombocytopenic purpura, decreased blood pressure, vasculitis, severe bleeding, granulocytopenia, agranulocytosis, anemia (including aplastic), pancytopenia, severe thrombocytopenia, bleeding in the surgical wound;
- from the gastrointestinal tract: often - abdominal pain, diarrhea, dyspepsia, gastrointestinal bleeding; infrequently - flatulence, nausea, gastritis, constipation, vomiting, stomach and duodenal ulcers; rarely - retroperitoneal hemorrhage; very rarely - stomatitis, colitis (including lymphocytic and ulcerative colitis), deviation of liver function tests, acute liver failure, pancreatitis, hepatitis, retroperitoneal hemorrhage and gastrointestinal bleeding up to death;
- from the respiratory system: often - nosebleeds; very rarely - interstitial pneumonitis, bronchospasm, bleeding from the respiratory tract (hemoptysis, pulmonary hemorrhage);
- from the central nervous system: infrequently - paresthesia, dizziness, headache, intracranial hemorrhage; rarely - dizziness; very rarely - a disorder of taste, confusion, hallucinations;
- from the musculoskeletal system: very rarely - myalgia, arthritis, hemarthrosis, arthralgia;
- from the urinary system: infrequently - hematuria; very rarely - increased serum creatinine, glomerulonephritis;
- on the part of the skin: often - a bruise; infrequently - purpura, pruritus, rash; very rarely - urticaria, lichen planus, eczema, erythematous rash, bullous dermatitis, angioedema;
- allergic reactions: very rarely - serum sickness, anaphylactoid reactions;
- others: often - bleeding at the injection sites; infrequently - eye hemorrhages (including in the tissue of the eye and in the conjunctiva); very rarely - fever.
Overdose
In case of an overdose of Tromborel, bleeding may develop, bleeding time may be prolonged, and future complications in the form of bleeding may occur. These conditions require appropriate treatment. If it is necessary to quickly correct the increased bleeding time, platelet transfusion is performed.
special instructions
The entire period of Tromborel's use requires monitoring of the hemostatic system indicators: the number of platelets, activated partial thromboplastin time, and the functional activity of platelets. It is also necessary to regularly monitor the activity of liver functions.
With caution, Tromborel should be used in patients with a high risk of severe bleeding (in the case of surgery or injury), as well as in persons with injuries from which bleeding may open (gastrointestinal and intraocular pathologies). Caution should be observed when treating patients receiving the following drugs: heparin, NSAIDs, ASA, GP IIb / IIIa inhibitors. Patients should be closely monitored to identify possible signs of developing bleeding (including latent) in time, especially in the first weeks at the beginning of treatment, after surgical interventions and invasive procedures. When warfarin is taken together, bleeding may increase, so this combination is not recommended.
For planned surgery, when antiplatelet action is undesirable, Tromborel should be canceled 7 days before surgery. All patients should tell their doctor about each episode of bleeding as it takes longer than usual to stop. All patients who are to undergo surgery must inform the doctor about taking Tromborel.
There are rare cases of thrombotic thrombocytopenic purpura during treatment with clopidogrel, even short-term. This condition is potentially life-threatening, and therefore requires immediate appropriate treatment, including the use of plasmapheresis. It is characterized by microangiopathic hemolytic anemia and thrombocytopenia in combination with fever, renal impairment, and neurological disorders.
Tromborel should not be used in acute ischemic stroke, i.e., during the first 7 days, as there is no data on its effectiveness and safety.
Influence on the ability to drive vehicles and complex mechanisms
The influence of Tromborel on the reaction rate and the ability to concentrate is insignificant or absent at all.
Application during pregnancy and lactation
Do not use Tromborel to treat pregnant and breastfeeding women.
Pediatric use
Clopidogrel is contraindicated in children and adolescents under the age of 18.
With impaired renal function
In patients with functional impairment of the kidneys, experience with clopidogrel is limited, therefore, Tromborel should be used with caution.
For violations of liver function
In severe functional disorders of the liver, Tromborel is contraindicated.
The drug should be used with caution, under close medical supervision, in the treatment of patients with moderate hepatic impairment.
Use in the elderly
Patients over the age of 75 years do not adjust the dosage regimen of Tromborel, but do not use the drug in the first loading dose.
Drug interactions
There were no clinically significant drug interactions with the combined use of atenolol, nifedipine or both of these drugs simultaneously with Tromborel.
There was no significant change in the pharmacodynamic activity of clopidogrel when it was combined with estrogens, cimetidine, phenobarbital, antacids, coronary vasodilators, GP IIb / IIIa receptor blockers, antiepileptic drugs, hypolipidemic agents, diuretics, inhibitors of angiotensin insulin), slow calcium channel blockers, drugs for hormone replacement therapy, beta-blockers.
Tromborel enhances the antiplatelet activity of thrombolytics, ASA, NSAIDs, indirect anticoagulants, heparin. Because of this, the risk of developing bleeding (including gastrointestinal) increases. In this connection, combination therapy should be carried out with extreme caution.
It is not recommended to combine Tromborel with warfarin because of the risk of increased bleeding. Caution should be exercised while taking GP IIb / IIIa inhibitors. Clopidogrel does not affect the properties of theophylline and digoxin.
If necessary, Tromborel can be used in patients receiving tolbutamide or phenytoin.
Experts advise avoiding the simultaneous use of clopidogrel with powerful and moderate inhibitors of the CYP2C19 system (for example, with omeprazole). If the appointment of proton pump inhibitors is required, the choice should be given to drugs that have the least inhibitory activity against the CYP2C19 isoenzyme, for example, pantoprazole.
Analogs
Tromborel's analogs are Agrenox, Aspirin Cardio, ASK-cardio, Brilinta, Detromb, Integrilin, Cardiomagnil, Clopigrant, Clopidogrel, Koromax, Lopirel, Plavix, Sanovask, Trombital, Trombomag, Fluder, Effient, Egithromb and others.
Terms and conditions of storage
Store at a temperature not exceeding 25 ° C in a dry, dark place. Keep out of the reach of children.
The shelf life is 3 years.
Terms of dispensing from pharmacies
Dispensed by prescription.
Reviews about Tromborel
There are no reviews directly about Tromborel. However, there are many reports of other drugs containing clopidogrel as an active component. All of them are positive: the drug is effective in the prevention of atherothrombotic disorders, is well tolerated, the drugs are affordable and are sold in all pharmacy chains.
Price for Tromborel in pharmacies
The price of Tromborel 75 mg is approximately 428 rubles. for a pack of 14 film-coated tablets.
Maria Kulkes Medical journalist About the author
Education: First Moscow State Medical University named after I. M. Sechenov, specialty "General Medicine".
Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!
