Description
Description
Dosage 250 mg: film-coated tablets, white or almost white, round, biconvex. On a slice of white or almost white.
Pharmacological action
Antifibrinolytic agent. Tranexamic acid specifically inhibits the activation of profibrinolysin (plasminogen) and its conversion to fibrinolysin (plasmin). The antifibrinolytic activity of tranexamic acid is about 10 times higher than the activity of epsilon-aminocaproic acid.
Tranexamic acid has a local and systemic hemostatic effect in bleeding associated with increased fibrinolysis. In addition, tranexamic acid has an analgesic, anti-allergic and anti-inflammatory effect due to the suppression of the formation of kinins and other active peptides involved in allergic and inflammatory reactions.
Pharmacokinetics:
Oral absorption in the range of 0.5-2 g is 30-50%. The time to reach the maximum concentration when ingesting 0.5 1 and 2 g of tranexamic acid is 3 hours, the maximum concentration is 5, 8 and 15 μg / ml, respectively. Eating does not affect the absorption of tranexamic acid in the gastrointestinal tract.
Communication with plasma proteins (profibrinolysin) – less than 3%. Tranexamic acid does not bind to albumin. The therapeutic concentration of tranexamic acid in blood plasma is 5-10 mg / l.
Distributed in tissues relatively evenly (the exception is cerebrospinal fluid, where the concentration is 1/10 of the plasma) penetrates the placental barrier, into breast milk (about 1% of the concentration in the mother s plasma), through the blood-brain barrier, into the intraarticular fluid and synovial membranes . The initial distribution volume is 9-12 liters. The antifibrinolytic concentration in various tissues persists for 17 hours, in plasma – up to 7-8 hours.
Metabolized to a small extent. The pharmacokinetic curve has a three-phase shape with a half-life in the final phase of 3 hours. The total renal clearance is equal to the plasma (7 l / h). It is excreted by the kidneys (the main way is glomerular filtration) – more than 95% unchanged during the first 12 hours.
2 metabolites of tranexamic acid were identified: N-acetylated idamenated derivative.
After taking tranexamic acid orally at a dose of 10-15 mg / kg during the first hour, 3 hours, 24 hours and 48 hours, 1%, 7%, 39% and 79% of the dose taken, respectively.
In case of impaired renal function, there is a risk of cumulation of tranexamic acid.
Indications
Short-term treatment of bleeding associated with increased fibrinolysis in the following pathological conditions:
– Prostatectomy bladder surgery
– Menorrhagia
– Epistaxis
– Cervical conization
– Traumatic hyphema (hemorrhage in the anterior chamber of the eye).
– Prevention and treatment of bleeding in patients with hemophilia who undergo minor surgery (including tooth extraction).
– Hereditary angioedema (prevention of exacerbations of the disease).
Contraindications
– Hypersensitivity to tranexamic acid or other components of the
preparation – Severe chronic renal failure (glomerular filtration rate [GFR] less than 30 mg / ml / 1.73 m2) due to the risk of
cumulation – Venous or arterial present or history (deep vein thrombosis of the legs, pulmonary thromboembolism, intracranial thrombosis, etc. ) when simultaneous therapy with
anticoagulants is not possible – Fibrinolysis due to consumption coagulopathy (hypocoagulation stage of disseminated intravascular coagulation syndrome [DIC]) and cerebral infarction)
– Treatment of menorrhagia in patients under the age of 16 years (no experience with use)
– Children under 3 years of age (solid drug orma).
Caution:
Tranexamic acid should be used with caution in the following situations:
– Hematuria caused by kidney parenchyma diseases, and bleeding from the upper urinary tract (risk of secondary mechanical obstruction of the urinary tract with a blood clot with the development of anuria) (See Special Instructions)
– Patients with a high risk of thrombosis (history of thromboembolic events or a family history of thromboembolic disease), verified
– Disseminated intravascular coagulation syndrome [DIC]
– The presence of blood in cavities, for example, in the pleural cavity, joint cavities and urinary tract
– Patients receiving anticoagulant therapy (limited experience)
– Concomitant use of coagulation factor II, VII, IX, and X drugs in combination with [prothrombin complex] or anti-inhibitory coagulant complex (See Interaction with other medicines section)
– Patients taking combined oral contraceptives (due to the increased risk of venous thromboembolic complications and arterial thrombosis) (See Interaction with other medicines section).
Directions for use
Inside, regardless of food intake.
– Short-term treatment of bleeding due to increased fibrinolysis: the recommended standard dose of tranexamic acid is 15-25 mg / kg body weight, on average 1000-1500 mg 2-3 times a day.
– For prostatectomy and surgery on the bladder: 1000 mg 6 hours before surgery, then 1000 mg 3-4 times a day until macrohematuria disappears. The use of the drug for more than 2 weeks after surgery is not recommended.
– For menorrhagia: the recommended daily dose is 1000 mg 3 times a day until the cessation of menorrhagia, but not more than 4 days. With profuse bleeding, the dose of the drug can be increased, while the total daily dose should not exceed 4000 mg. Tranexamic acid treatment should not be started before menstruation occurs. In clinical studies, tranexamic acid has not been used for more than three menstrual cycles in a row.
– For recurrent nosebleeds: 1000 mg 3 times a day for 7 days.
– After cervical conization surgery: 1500 mg 3 times a day for 12 days after surgery.
– For traumatic hyphema: 1000-1500 mg 3 times a day (target dose of 25 mg / kg body weight) for 7 days.
– Patients with hemophilia: the drug is prescribed orally at a dose of 25 mg / kg body weight 2 hours before tooth extraction, and then 1000-1500 mg 3 times a day for 6-8 days. Coagulation factors VIII or IX should be prescribed at the same time.
– In case of hereditary angioedema: 1000-1500 mg 2-3 times a day. If the patient can predict an exacerbation of the disease, the drug can be taken intermittently, depending on the presence of prodromal symptoms. In other cases, the drug should be taken continuously.
Use of the drug in special groups of patients
Impaired renal function
In patients with mild to moderate impaired renal excretory function, dose and dosage rates of tranexamic acid should be adjusted:
Serum creatinine concentration
Glomerular filtration rate (GFR)
Dose of tranexamic acid
Multiplicity of intake
120-249
mmol / l
(1.36-2.82
mg / dl)
60-89 minrd / 1.73 m2
15 mg / kg body weight
2 times a day
250-500
Ñmol / l
(2.83-5.66
mg / dl)
30-59
ml / min / 1, 73 m2
15 mg / kg body weight
once a day
Impaired liver function
Dose adjustment is not required in patients with impaired liver function.
Elderly
In elderly patients, in the absence of renal failure, dose adjustment is not required.
Children’s age
Data on the efficacy and safety of tranexamic acid preparations in children is limited.
In children, tranexamic acid is prescribed at the rate of 25 mg / kg body weight 2-3 times a day.
Actions to skip taking the next dose of
If you skip taking one dose, you must take the next dose of the drug at the scheduled time. Do not take a double dose after skipping the next dose.
Special instructions
In patients with hereditary angioedema before treatment, an ophthalmologist should be consulted (determination of visual acuity, color vision, fundus condition). In the process of treatment, a regular ophthalmic examination is required (including an assessment of visual acuity and color perception, examination of the fundus with a slit lamp, measurement of intraocular pressure, assessment of visual fields). If visual disturbances occur during treatment with tranexamic acid, the drug must be discontinued.
In patients with hereditary angioedema who have been taking tranexamic acid preparations for a long time, regular laboratory monitoring of liver function is necessary.
Tranexamic acid preparations should be used with caution in case of hematuria caused by kidney parenchyma diseases, since in these conditions intravascular precipitation of fibrin is often observed, which can aggravate kidney damage. In addition, in cases of massive bleeding of any etiology from the upper urinary tract, antifibrinolytic therapy increases the risk of blood clots in the renal pelvis and / or ureter and, accordingly, secondary mechanical obstruction of the urinary tract and the development of anuria.
Although clinical trials have not revealed a significant increase in the incidence of thrombosis, the risk of thrombotic complications cannot be completely excluded. Cases of development of venous and arterial thrombosis and thromboembolism in patients treated with tranexamic acid are described.
In addition, cases of occlusion of the central retinal artery and central retinal vein have been reported. Several patients developed intracranial thrombosis during treatment with tranexamic acid. Accordingly, in patients at high risk of developing thrombosis (a history of thromboembolic complications, cases of thromboembolism in relatives, verified diagnosis of thrombophilia) tranexamic acid should be used only in case of emergency and under strict medical supervision. Before using tranexamic acid, an examination should be conducted aimed at identifying risk factors for thromboembolic complications.
The presence of blood in cavities, for example, in the pleural cavity, joint cavities and urinary tract (including in the renal pelvis and urinary bladder) can lead to the formation of an insoluble clot in them due to extravascular coagulation, which may be physiological resistant fibrinolysis.
Patients with irregular menstrual bleeding should not be prescribed granexamic acid until the cause of dysmenorrhea has been established. If the amount of menstrual bleeding is inadequately reduced during treatment with tranexamic acid, alternative treatment should be considered.
The efficacy and safety of tranexamic acid preparations in the treatment of menorrhagia in patients younger than 16 years of age have not been established.
Use tranexamic acid with caution in women taking concomitant oral contraceptives at the same time, due to the increased risk of thrombosis (See Interaction with other drugs).
In patients with DIC, who need treatment with tranexamic acid, therapy should be carried out under the close supervision of a doctor with experience in treating this disease.
Due to the lack of adequate clinical studies, the simultaneous use of tranexamic acid with anticoagulants should be carried out under the close supervision of a specialist, experienced in the treatment of coagulation disorders.
If there is a visual impairment while taking tranexamic acid, you must stop taking the drug and consult a doctor.
Impact on the ability to drive transp. Wed and fur .:
The ability of tranexamic acid to influence the rate of psychomotor reactions and the ability to drive vehicles or other mechanical means has not been studied. Tranexamic acid can cause dizziness and visual impairment, and, accordingly, can affect the ability to engage in potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions.
Composition
Active ingredient:
tranexamic acid – 250 mg.
Excipients:
microcrystalline cellulose – 45.05 mg,
pregelatinized starch – 4.85 mg,
carboxymethyl starch sodium – 6.20 mg,
talc – 7.99 mg,
silicon dioxide colloidal dioxide, 6 mg – 6
sodium stearyl fumarate – 9.90 mg.
Shell:
VIVACOAT ® RA-1P-000 [hypromellose 6 cps (hydroxypropyl methylcellulose 6 cps) – 3.51 mg, titanium dioxide – 2.70 mg, polydextrose (E1200) – 1.35 mg, talc – 0.90 mg polyethylene glycol-3350 – 0.54 mg.
Side effects of
Given the experience with gliclazide and other sulfonylurea derivatives, the following side effects should be considered.
Hypoglycemia
The most common adverse reaction with gliclazide is hypoglycemia. Like other drugs of the sulfonylurea group, the Gliclad® preparation can cause hypoglycemia in case of irregular food intake and especially if food intake is missed.
Possible symptoms of hypoglycemia: headache, severe hunger, nausea, vomiting, increased fatigue, sleep disturbance, irritability, agitation, decreased concentration, loss of self-control, feeling of helplessness, delayed reaction, depression, confusion, impaired vision and speech, aphasia, tremor, paresis, impaired perception, dizziness, weakness, convulsions, bradycardia, delirium, shallow breathing, drowsiness, loss of consciousness with the possible development of coma, up to the death.
Adrenergic reactions may also be noted: increased sweating, clammy skin, anxiety, tachycardia, increased blood pressure, palpitations, arrhythmia, and angina pectoris.
Typically, symptoms of hypoglycemia are stopped by taking carbohydrates (sugar). Taking sweeteners is ineffective. Against the background of other sulfonylurea derivatives, relapses of hypoglycemia were noted after its successful relief.
In severe or prolonged hypoglycemia, emergency medical care is indicated, possibly with hospitalization, even if there is an effect from taking carbohydrates.
Other side effects of
From the gastrointestinal tract: abdominal pain, nausea, vomiting, diarrhea, constipation. Taking the drug during breakfast avoids these symptoms or minimizes them.
The following side effects are less common: – on the part of the skin and subcutaneous tissues: skin rash, itching, urticaria, Quincke’s edema, erythema, maculopapular rash, bullous reactions (such as Stevens-Johnson syndrome and toxic epidermal necrolysis), in some cases, drug rash with eosinophilia and systemic manifestations (DRESS syndrome)
– from the blood and lymphatic system: hematological disorders (anemia, leukopenia, thrombocytopenia, granulocytopenia) are rare. As a rule, these phenomena are reversible in case of termination of
therapy – from the liver and biliary tract: increased activity of hepatic enzymes (aspartate aminotransferase (ACT), alanine aminotransferase (ALT), alkaline phosphatase), hepatitis (isolated cases). If cholestatic jaundice occurs, therapy should be discontinued.
These adverse reactions are usually reversible if therapy is discontinued: – on the part of the organ of vision: there may be transient visual disturbances caused by a change in blood glucose concentration, especially at the beginning of
therapy – side effects inherent in sulfonylurea derivatives: as with other sulfonylurea derivatives the following side effects were noted: erythrocytopenia, agranulocytosis, hemolytic anemia, pancytopenia, allergic vasculitis, hypopatraemia.
Increased activity of liver enzymes, impaired liver function (e.g. with the development of cholestasis and jaundice) and hepatitis, manifestations decreased over time after discontinuation of sulfonylurea preparations, but in some cases led to life-threatening liver failure.
Adverse Effects Reported in Clinical Trials
In a clinical study, there was a slight difference in the frequency of various serious adverse events between the two groups of patients. No new safety data has been received.
A small number of patients had severe hypoglycemia, but the overall incidence of hypoglycemia was low. The incidence of hypoglycemia in the intensive glycemic control group was higher than in the standard glycemic control group. Most episodes of hypoglycemia in the intensive glycemic control group were observed against the background of concomitant insulin therapy.according to available data).
Disorders of the gastrointestinal tract: often – nausea, vomiting, diarrhea (symptoms go away when the dose is reduced).
Disorders of the skin and subcutaneous tissues: rarely – skin allergic reactions, including allergic dermatitis.
Violations of the organ of vision: rarely – visual impairment, incl. violation of color perception, retinal vascular thrombosis.
Vascular disorders: rarely – thromboembolic complications, marked decrease in blood pressure (usually due to excessively fast intravenous administration, in exceptional cases after oral administration) very rarely – arterial and venous thromboses of various localization, frequency is unknown – acute myocardial infarction, cerebral artery thrombosis, carotid artery thrombosis, stroke, deep vein thrombosis of the legs, pulmonary embolism, renal artery thrombosis with the development of cortical necrosis and acute renal failure, occlusion of the aorto-coronary shunt, thrombosis of the central artery and retinal vein.
Disorders of the immune system: very rarely – hypersensitivity reactions, incl. anaphylactic shock.
Disorders of the nervous system: rarely – dizziness of convulsions (usually with intravenous administration).
Drug Interactions
No specific clinical studies investigating the interactions of tranexamic acid with other drugs have been conducted. Tranexamic acid prevents the development of the pharmacological effect of fibrinolytic (thrombolytic) drugs.
Combined oral contraceptives increase the risk of venous thromboembolic complications and arterial thrombosis (in particular, ischemic stroke and myocardial infarction).
There is no experience with tranexamic acid in women taking combined oral contraceptives.
Since tranexamic acid has an antifibrinolytic effect, simultaneous use with combined oral contraceptives can lead to an additional increase in the risk of thrombotic complications.
Concomitant use of tranexamic acid with coagulation factor II, VII drugs, IX and X in combination [prothrombin complex] or anti-inhibitory coagulant complex increases the risk of thrombosis.
Possible increased risk of thrombotic complications (in particular, myocardial infarction) with the simultaneous use of tranexamic acid with hydrochlorothiazide, desmopressin, ampicillin-sulbactam, ranitidine and nitroglycerin.
When combined with hemostatic drugs, thrombosis can be activated.
Concomitant use of tranexamic acid with anticoagulants should be carried out under the strict supervision of a physician (experience with use is limited).
Overdose
There is limited evidence of overdose cases. One case of overdose has been reported (taking 37 g of tranexamic acid).
Symptoms: dizziness, headache, nausea, vomiting, diarrhea, orthostatic symptoms (including dizziness when moving from horizontal to vertical), orthostatic arterial hypotension. In predisposed patients, the risk of thrombosis is increased.
Treatment: antidote unknown. If an overdose of tranexamic acid is suspected, hospitalization is necessary. When assisting, induce vomiting, then gastric lavage. Activated carbon reduces the absorption of tranexamic acid when taken orally during the first 1-2 hours after an overdose.
If the patient is unconscious or if swallowing is impaired, activated charcoal can be injected through a nasogastric tube. Intake or parenteral administration of a large amount of fluid to enhance renal excretion, forced diuresis, control of the amount of urine excreted is recommended. B n
lekarstvennaja form
tablets
Appointment
Adults doctor’s prescription
Indications
From nosovogo krovotecheniya, From krovotecheniya
