Active ingredient: tranexamic acid;

1 ml of the solution contains 50 mg of tranexamic acid;

Excipients: water for injections.

Solution for injection.

Physical and chemical properties: clear or almost clear colorless or with light-brown tint liquid.

Fibrinolysis inhibitors. Code АТХ B02A A02.

Pharmacodynamic properties.

Tranexamic acid is the antifibrinolytic product which specifically inhibits the activation of  profibrinolysin (plasminogen) and its conversion into fibrinolysin (plasmin). The product demonstrates local systemic hemostatic effect during hemorrhages related to fibrinolysis increase (thrombocytes pathology, menorrhagia).

Moreover, by restraining the creation of kinines and other active peptides taking part in allergic and inflammatory reactions, tranexamic acid has anti-inflammatory, anti-allergic, anti-infection and anti-oncology effects.

There are clinically proven data on analgesic activity of tranexamic acid and its ability to facilitate the analgesic effect of opiates.

Pharmacokinetic properties.

The product distributes into the tissues more or less homogenously (except for cerebro-spinal fluid, where product’s concentration is 1/10 of plasma); penetrates through brain-blood and placental barrier into mother’s milk (approximately 1% of the concentration in mother’s plasma). Tranexamic acid is found in seminal fluid where it decreases fibrinolytic activity, but does not influence upon spermatozoids migration. The initial volume of distribution is 9-12 l. Less than 3% of tranexamic acid bind with plasma proteins (profibrinolysin).

Antifibrinolytic concentration in different tissues is maintained within 17 hours and 7-8 hours in plasma.

Only minute quantity  is metabolized. “Concentration-time” curve consists of three phases with half-life period in terminal phase which equals to 2 hours. General kidney clearance is the same as plasmatic one (7 l/h).

The substance is excreted by kidneys ( glomerular filtration) : almost 95% are excreted intactly within the first 12 hours.

2 metabolites of tranexamic acid were identified (N-acetylized and desamitizated).

There is a risk of tranexamic acid accumulation among the patients with kidney dysfunction.

Indications.

Hemorrhages or danger of hemorrhages due to general fibrinolysis (hemorrhage during operations or postoperative period, postpartum hemorrhage, manual removal of afterbirth, chorion detachment, hemorrhage during pregnancy, malignant tumor in pancreatic and prostatic gland, hemophilia, hemorrhagic complications caused by fibrinolytic therapy, thrombocytopenic purpura, leucosis, hepatic disorders, preliminary streptokinase therapy) or local fibrinolysis (uterine, nasal, lung, gastrointestinal hemorrhages, hemorrhage caused by prostatectomy, cervical conization, tooth extraction for the patients having hemorrhagic diathesis). Surgical intervention into urinary bladder. Surgical treatment of the systemic inflammatory reaction (sepsis, peritonitis, necrosis of pancreas, severe and moderately severe gestational toxicosis, shock of various etiology etc.).

• Thromboembolic diseases in the past medical history;

• High risk of thrombus formation;

• Gross hematuria;

• Coagulopathy caused by diffusive inofexia (diffusive inofexia syndrome) not accompanied significant fibrinolysis activation.

• Myocardial infarction

• Subarachnoid hemorrhage;

• Severe kidney failure;

• Color-vision defect

• Hypersensitivity to the product.

To avoid arterial hypotension, slow administration is recommended, the dosage should not exceed 1 mg per minute.

Due to the insufficient number of data, highly active prothrombin complexes and other antifibrinolytic agents, anti-inhibitor coagulant complexes should not be administered with tranexamic acid. Tranexamic acid may be mixed with the most of solutions (electrolytes, glucose solution, anti-shock solution).

Heparin may be added during intravenous dropwise injection.

Conjoint therapy with chlorpromazine and tranexamic acid among the patients with  subarachnoid hemorrhagemay may result in cerebral vasospasm and cerebral ischemia or may decrease cerebral circulation.

Tranexamic acid is incompatible with urokinase, noradrenaline bitartrate, desoxyepinephrine hydrochloride, dipyridamole and diazepam.

Usually, tranexamic acid is intactly excreted with urine. Therefore, the dose and number of administrations should be reduced for the patients having kidney dysfunction.

In case of intravenous injection, the dose should be corrected accordingly (see section “Posology and method of administration”).

Due to the blood clots in urethra, there is a risk of mechanic anuria during the treatment of kidney hematuria.

There is a risk of venous and arterial thrombosis or thrombembolia among the patients intaking tranexamic acid. Moreover, tranexamic acid is not recommended for the patients with thromboembolic disease as there is a risk of venous or arterial thrombosis.

Tranemxamic acid should not be used with Factor IX complex or anti-inhibitor coagulant complex as there is a risk of thrombosis.

Conjoint therapy with chlorpromazine and tranexamic acid among the patients with  subarachnoid hemorrhagemay may result in cerebral vasospasm and cerebral ischemia or may decrease cerebral circulation.

In the course of treatment, the consultation with ophthalmologist is recommended within several days in order to check the visual acuity, field of view and color vision with the check of eye ground due to the risk of embolism of retinal vessel and central retinal vein.

There are no adequate clinical data on safety of  use of tranexamic acid in pregnant women. However, the data on absence of teratogenic and embryotoxic effects have been reported. Also there are the data on usage of tranexamic acid in connection with hemostatic therapy  during I-II trimesters with threatened miscarriage which give an opportunity to eliminate the threatened miscarriage and ensure the normal pregnancy.

The product is used during delivery and caesarean section in ordinary doses.

Tranexamic acid may enter the mother’s milk in small amounts ((< 0,01 %). Therefore, the product may be administered during lactation.

When used in prescribed doses, Haemexam is likely to cause dizziness and arterial hypotension, decrease in color vision or visual acuity. Therefore, driving machine and use of complex mechanisms which require concentration and fast reaction are not recommended within the course of treatment.

Intravenous administration (dropwise or bolus injection)

Dose schedule is set individually depending on clinical settings.

General fibrinolysis:  administration of a single dose 15 mg/ of patient’s bodyweight each 6-8 hours at the rate of 1 ml/min.

Local fibrinolysis: administration of 200-500 mg of the product  2-3 times per day.

Prostatectomy, urinary bladder surgery:

Administration of 1 g during operation, then 1 g each 8 hours within 3 days. Then the product should be administered  in form of tablets until gross hematuria is eliminated.

In the event of high risk of hemorrhage during systemic inflammatory reaction, the dose of 10-11 mg/kg should be administered 20-30 minutes before the surgery.

Patients with coagulopathy are administered with 10 mg/kg of bodyweight before tooth extraction; administration of the tranexamic acid in the form of tablets after tooth extraction.

In the event of decreased excretory function of kidneys, the following correction of the dose schedule is recommended:

• creatinine in blood with concentration of 120-250 mcmol/l: 10 mg/kg 2 times per day;
• 250-500 mcmol/l – 10 mg/kg 1 time per day;
• over 500 mcmol/l – 5 mg/kg 1 time per day.

Children.

Maximum single dose should not exceed 10 mg/kg of the patient’s bodyweight. Maximum daily dose should be 20 mg/kg of the patient’s bodyweight.

When used in large doses, the product may cause nausea, vomiting and orthostatic hypotension.

Treat symptomatically. Forced diuresis is recommended. Maintenance of fluid-and-electrolyte balance is strongly recommended.

Immune system disorders: allergic reactions (rash, itch, urticarial).

Gastrointestinal disorders: anorexia, nausea, vomiting, heartburn, diarrhea.

Cardiac disorders: tachycardia, thoracodynia, arterial hypotension (in case of fast intravenous injection).

Visual organs disorders: color-vision defect, blurred vision.

Blood and lymphatic system disorders: thrombosis or thromboembolism (minimal risk).

General disorders: dizziness, lack of energy, drowsiness.

2 years.

Store in original package at the temperature not above 25°C. Keep away from children. Do not freeze.

Haemaxam is not compatible with  blood products, solution containing penicillin, hypertensive products (norepinefrin, bitartrate, desoxyepinephrine hydrochloride, dipyridamole and diazepam). Not compatible with urokinase, unless used as antidote upon its overdose.

5 ml in ampules No. 10, No. 50 in carton folding box.

10 ml in ampules No. 5, No. 10 in carton folding box.

Following the doctor’s prescription.