Instructions for Trenax 500 film-coated tablets 500 mg No. 12
Composition
active ingredient: tranexamic acid;
1 tablet contains 250 mg or 500 mg of tranexamic acid;
Excipients: microcrystalline cellulose, povidone, croscarmellose sodium, colloidal anhydrous silica, talc, magnesium stearate, titanium dioxide (E 171), hypromellose, propylene glycol, diethyl phthalate.
Dosage form
Film-coated tablets.
Main physicochemical properties:
250 mg tablets: round biconvex tablets, white or almost white, coated, smooth on both sides;
500 mg tablets: round, biconvex, white or almost white, film-coated tablets, smooth on one side and with a breakline on the other.
Pharmacotherapeutic group
Antihemorrhagic agents. Fibrinolysis inhibitors.
ATX code B02A A02.
Pharmacological properties
Pharmacodynamics.
Antifibrinolytic agent. Tranexamic acid specifically inhibits the activation of profibrinolysin (plasminogen) and its conversion to fibrinolysin (plasmin). It has a local and systemic hemostatic effect in bleeding associated with increased fibrinolysis (platelet pathology, menorrhagia). Tranexamic acid also has antiallergic and anti-inflammatory effects by inhibiting the formation of kinins and other active peptides involved in allergic and inflammatory reactions.
Pharmacokinetics.
Absorption with oral administration of doses in the range of 0.5–2 g is 30–50%. TCmax with oral administration of 0.5 g, 1 g and 2 g is 3 hours, Cmax is 5, 8 and 15 μg/ml, respectively. Binding to blood plasma proteins (profibrinolysin) is not less than 3%.
It is distributed in tissues relatively evenly (except in cerebrospinal fluid, where the concentration is 1/10 of the plasma concentration); penetrates the placental barrier and into breast milk (about 1% of the concentration in maternal plasma). It is found in seminal fluid, where it reduces fibrinolytic activity, but does not affect sperm migration. The initial volume of distribution is 9–12 l. Antifibrinolytic concentration in various tissues is maintained for 17 hours, in blood plasma – up to 7–8 hours.
A small part is metabolized. The AUC curve has a triphasic shape with T1/2 in the final phase – 3 hours. Total renal clearance is equal to plasma (7 l/h). Excreted by the kidneys (the main route is glomerular filtration) – about 95% in unchanged form during the first 12 hours.
Two metabolites of tranexamic acid have been identified: the N-acetylated and deaminated derivatives. In cases of impaired renal function, there is a risk of accumulation of tranexamic acid.
Indication
Bleeding or risk of bleeding with increased fibrinolysis, both generalized (bleeding during surgery and in the postoperative period on the prostate gland, hemorrhagic complications of fibrinolytic therapy) and local (uterine, gastrointestinal, nasal bleeding, post-traumatic hyphema, bleeding after prostatectomy or bladder surgery, tonsillectomy, conization of the cervix, tooth extraction in patients with hemophilia).
Hereditary angioedema.
Contraindication
Hypersensitivity to the drug or to other components of the drug, severe renal failure, macroscopic hematuria, high risk of thrombosis, thrombophlebitis; active thromboembolic disease, venous or arterial thrombosis in history; myocardial infarction, subarachnoid hemorrhage, acute venous or arterial thrombosis; fibrinolytic states after coagulopathy due to exhaustion, except for excessive activation of the fibrinolytic system in acute severe bleeding; history of seizures; impaired color perception.
Interaction with other medicinal products and other types of interactions
Tranexamic acid is incompatible with urokinase, norepinephrine bitartrate, deoxyepinephrine hydrochloride, metarmin bitartrate, dipyridamole, diazepam. Highly active prothrombin complexes and antifibrinolytic agents, antiinhibitory coagulation complexes should not be used simultaneously with tranexamic acid. The combination of chlorpromazine and tranexamic acid should be avoided in patients with subarachnoid hemorrhage; this may lead to cerebral vasospasm and cerebral ischemia and, possibly, to a decrease in cerebral blood flow; the symptomatic properties of both drugs may contribute to the development of vasospasm and cerebral ischemia in these patients. Tranexamic acid should be used with caution in patients using oral contraceptives, since the risk of thrombosis is increased.
Application features
In renal failure (depending on the degree of increase in serum creatinine), reduce the dose and number of injections. In patients with impaired renal function, the drug concentration in the blood plasma is increased. Therefore, it is recommended to reduce the dose in such patients. Urinary obstruction due to the formation of a clot with a bleeding source in the upper urinary tract has been reported in patients using the drug. Cases of venous and arterial thrombosis or thromboembolism have been reported in patients using tranexamic acid. In addition, cases of occlusion of the central retinal artery and central retinal vein have been reported. Patients using the drug for more than a few days are recommended to undergo an ophthalmological examination, including checking visual acuity, color perception, fundus, visual fields, and monitoring liver function.
Patients with visual impairment should discontinue treatment.
Patients with thromboembolic disease may be at increased risk for venous or arterial thrombosis.
Tranexamic acid should not be used concomitantly with Factor IX complex or anti-inhibitor coagulation complexes, as the risk of thrombosis may be increased.
The drug should not be used in patients with disseminated intravascular coagulation.
Tranexamic acid should not be used in patients with increased fibrinolysis resulting from disseminated intravascular coagulation.
Tranexamic acid has been found in semen at fibrinolytic concentrations, but it does not affect sperm motility. Clinical studies have not shown any effect on fertility.
Convulsions have been reported with the use of tranexamic acid. Most of these cases have been reported after intravenous administration of high doses of tranexamic acid during coronary artery bypass grafting (CABG). When using the recommended low doses of tranexamic acid, the incidence of postoperative seizures is similar to that in patients not receiving tranexamic acid.
Patients with irregular menstrual bleeding should not use tranexamic acid until the cause of the bleeding is determined. If tranexamic acid does not reduce the intensity of menstrual bleeding, alternative treatment should be considered.
Patients with previous thromboembolic events and patients with a family history of thromboembolic diseases (patients with thrombophilia) should use the drug according to strict medical indications under close medical supervision.
There is no clinical experience with the use of tranexamic acid for the treatment of menorrhagia in children under 15 years of age.
Cases of seizures have been reported in association with tranexamic acid treatment. In cardiac surgery, most of these cases have been reported following high-dose intravenous tranexamic acid.
Use during pregnancy or breastfeeding
Tranexamic acid crosses the placenta and into breast milk. Studies on the safety of the drug during pregnancy have not been conducted, therefore, during this period, the drug can be prescribed only when the expected benefit to the mother outweighs the potential risk to the fetus or child. If necessary, the use of the drug during lactation should be considered to discontinue breastfeeding.
Ability to influence reaction speed when driving vehicles or other mechanisms
While using the drug, you should refrain from driving or operating complex machinery.
Method of administration and doses
Adults should be given the drug orally, regardless of meals.
Local fibrinolysis: recommended dose is 1–1.5 g 2–3 times a day.
Prostatectomy: For the prevention and treatment of hemorrhage in patients at increased risk before or after surgery, tranexamic acid should be administered as an injection; then administered as tablets of 1 g (2 tablets of 500 mg) 3–4 times a day until the disappearance of macroscopic hematuria.
Menorrhagia: recommended dose – 1 g 3 times a day for no more than 4 days. In case of prolonged menstrual bleeding, the dose should be increased, but not higher than the maximum dose – 4 g per day (8 tablets of 500 mg). It is not necessary to start treatment with the drug before the onset of menstrual bleeding.
Nosebleeds: 1 g 3 times a day for 7 days.
Cervical conization: 500 mg 3 times a day for up to 12 days.
Post-traumatic hemiplegia: the recommended dose of the drug is 1 g 3 times a day orally.
Hereditary angioedema: some patients are aware of the course of exacerbations of the disease, for them it is usually enough to take 1-1.5 g 2-3 times a day for several days. Other patients should use the drug in the same dose for a long time, depending on the course of the disease.
Tooth extraction in patients with hemophilia: The recommended dose is 25 mg/kg of tranexamic acid orally every 8 hours, starting 1 day before surgery and continuing for 2–8 days after surgery.
Patients with renal impairment.
Dose adjustment is necessary for patients with mild to moderate renal impairment according to plasma creatinine levels.
| Dosage |
| 120–249 μmol/L | 15 mg/kg 2 times a day |
| 250–500 μmol/L | 15 mg/kg once daily |
Elderly patients.
In the absence of renal excretory function disorders, dose adjustment is not required.
Children over 15 years of age should be prescribed the drug at a dose of 25 mg/kg of body weight.
The duration of treatment is usually 2–8 days.
Children.
There is no clinical experience with the use of tranexamic acid in children and adolescents under 15 years of age.
However, data on dosage, efficacy, and safety of use under these conditions are limited.
Overdose
Symptoms: nausea, vomiting, abdominal pain, orthostatic hypotension, hypotension, dizziness, headache, convulsions or increased manifestations of other adverse reactions.
Treatment: induce vomiting, then gastric lavage and administer activated charcoal. Maintain high fluid intake to promote renal excretion. There is a risk of thrombosis in individuals with a predisposition to thrombosis. Anticoagulant therapy should be considered.
Side effects
On the part of the digestive tract: nausea, vomiting, heartburn, diarrhea, which disappear when the dose is reduced, decreased appetite, abdominal pain.
Skin and subcutaneous tissue disorders: rash, itching, urticaria.
From the nervous system: drowsiness, dizziness, convulsions, especially with improper use.
On the part of the organs of vision: impaired color perception, visual impairment, seizures, congestive retinopathy, retinal vein/artery occlusion.
Immune system disorders: hypersensitivity reactions, including anaphylaxis.
Vascular disorders: arterial or venous thrombosis, thromboembolism, arterial hypotension.
Renal: acute renal cortical necrosis.
Expiration date
3 years.
Storage conditions
Store at a temperature not exceeding 25 °C in the original packaging.
Keep out of reach of children.
Packaging
6 tablets in a strip, 2 strips in a cardboard box.
Vacation category
According to the recipe.
Producer
McLeods Pharmaceuticals Limited.
Location of the manufacturer and its business address.
Phase II, Plot No. 12,15, 21, 23, 24, 25, 26, 27, 28, and 30, Survey No. 366, Premier Industrial Estate, Kachigam, Daman – 396210, India.
