Hemaxam

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT HEMAXAM (HAEMAXAM)

Composition:

Active substance: tranexamic acid;

1 ml of solution contains 50 mg of tranexamic acid;

Excipient: water for injections.

Pharmaceutical form. Solution for injection.

Main physico-chemical properties: a transparent or nearly transparent, colorless or slightly brownish liquid.

Pharmacotherapeutic group.

Fibrinolysis inhibitors. ATC code B02A A02.

Pharmacological Properties

Pharmacodynamics

Tranexamic acid is an antifibrinolytic agent that specifically inhibits the activation of profibrinolysin (plasminogen) and its conversion into fibrinolysin (plasmin). It exerts local and systemic hemostatic effects in bleeding associated with increased fibrinolysis (thrombocyte pathology, menorrhagia). Additionally, by suppressing the formation of kinins and other active peptides involved in allergic and inflammatory reactions, tranexamic acid produces anti-inflammatory, anti-allergic, anti-infective, and anti-tumor effects. Experimental studies have confirmed intrinsic analgesic activity of tranexamic acid, as well as its ability to enhance the pain-relieving effect of opioids.

Pharmacokinetics

Tranexamic acid is distributed relatively uniformly in tissues (except in cerebrospinal fluid, where concentrations are about 1/10 of plasma levels); it crosses the blood-brain and placental barriers and is excreted into breast milk (approximately 1% of maternal plasma concentration). It is detectable in seminal fluid, where it reduces fibrinolytic activity without affecting spermatozoa migration. The initial volume of distribution is 9–12 L. Less than 3% binds to plasma proteins (profibrinolysin).

Antifibrinolytic concentrations in various tissues are maintained for up to 17 hours, and in plasma for up to 7–8 hours.

Only a small fraction undergoes metabolism. The concentration–time curve is triphasic, with a terminal half-life of 2 hours. Total renal clearance equals plasma clearance (7 L/h).

Elimination is primarily renal (mainly via glomerular filtration): about 95% is excreted unchanged within the first 12 hours.

Two metabolites of tranexamic acid have been identified (N-acetylated and deaminated). In renal impairment, there is a risk of accumulation of tranexamic acid.

Clinical characteristics.

Indications.

Bleeding or risk of bleeding associated with enhanced fibrinolysis, either generalized (bleeding during surgery and in the postoperative period on the prostate gland, hemorrhagic complications of fibrinolytic therapy), or local (uterine, gastrointestinal bleeding, bleeding after prostatectomy, tonsillectomy, cervical conization, tooth extraction in patients with hemophilia).

Contraindications.

• Hypersensitivity to the drug;
• Subarachnoid hemorrhage;
• Severe renal insufficiency;
• Coagulopathy due to disseminated intravascular coagulation (DIC syndrome) without significant activation of fibrinolysis;
• Acute arterial or venous thrombosis;
• History of seizures;
• Fibrinolytic states following coagulopathy due to exhaustion, except for excessive activation of the fibrinolytic system during acute severe bleeding;
• Intrathecal and intraventricular applications (risk of brain edema and seizures);
• Color vision disturbances;
• Macroscopic hematuria;
• High risk of thrombosis;
• Thrombophlebitis;
• Myocardial infarction.

Special safety precautions.

To avoid arterial hypotension, the drug should be administered slowly, at a dose not exceeding 1 mg per minute.

Interaction with other medicinal products and other forms of interaction.

The drug can be used in combination with isotonic sodium chloride solution, glucose solution, 20% fructose solution, 10% invertase solution, dextran 40 or 70, Ringer's solution. Heparin may be added during intravenous infusion. When used in combination with heparin, the drug should be administered cautiously in patients with coagulation disorders.

Pharmaceutically incompatible with blood products, solutions containing penicillin, hypertensive agents (norepinephrine, desoxiepinephrine hydrochloride), tetracyclines, dipyridamole, diazepam. Incompatible with urokinase, except when used as an antidote after overdose of the latter.

There is a risk of increased thrombosis when used with estrogens. Do not use concomitantly with thrombolytics. Tranexamic acid is incompatible with metaraminol bitartrate.

Highly active prothrombin complex concentrates and antifibrinolytic agents, antithrombin 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 reduced cerebral blood flow; the pharmacological properties of both drugs may contribute to the development of vascular spasm and cerebral ischemia in these patients.

Special precautions.

Do not administer intramuscularly!

Thromboembolic risk factors must be assessed prior to administration. Patients with thromboembolic disease may be at increased risk of venous or arterial thrombosis. Cases of venous and arterial thrombosis or thromboembolism have been reported in patients receiving tranexamic acid.

Seizures have been reported during the use of tranexamic acid. Most of these cases occurred after intravenous administration of high doses of tranexamic acid during coronary artery bypass grafting (CABG). When recommended low doses of tranexamic acid are used, the incidence of postoperative seizures is the same as in patients not receiving tranexamic acid.

Visual disturbances may occur, including blurred vision and impaired color perception. If these symptoms occur, treatment should be discontinued. In addition, cases of central retinal artery occlusion and central retinal vein occlusion have been reported. After consultation with an ophthalmologist, the physician should decide whether continued use of the injection solution is warranted in patients with ophthalmological pathological conditions, especially retinal disorders.

Do not prescribe to patients taking oral contraceptives or estrogens due to increased risk of thrombosis.

Tranexamic acid should not be administered concomitantly with Factor IX complex or antithrombin-coagulation complexes, as this may increase the risk of thrombosis formation.

Patients with disseminated intravascular coagulation requiring treatment with tranexamic acid must be under the supervision of a physician experienced in managing such conditions.

Tranexamic acid has been detected in semen at fibrinolytic concentrations, but does not affect sperm motility. Clinical studies have not revealed any effect on fertility.

Use with caution in patients with thrombohemorrhagic complications (in combination with heparin and indirect anticoagulants), thrombosis (deep vein thrombophlebitis, thromboembolic syndrome, myocardial infarction) or risk of their development, impaired color vision, hematuria from upper urinary tract (possible obstruction by blood clots), or renal impairment (possible accumulation).

An ophthalmological examination assessing visual acuity, color vision, and fundus condition should be performed before and during treatment.

Use during pregnancy or breastfeeding.

Women of reproductive age should use effective contraception during treatment.

Tranexamic acid crosses the placenta and is excreted in breast milk. Adequate and well-controlled clinical studies on the safety of tranexamic acid use during pregnancy have not been conducted; therefore, the drug should be used during pregnancy only if the potential benefit to the mother outweighs the potential risk to the fetus. If use of the drug is necessary, a decision should be made regarding discontinuation of breastfeeding.

Ability to affect reaction speed when driving vehicles or operating machinery.

During administration of Hemaxam at usual doses, dizziness and arterial hypotension may occur, as well as impaired color vision and visual clarity. Therefore, during treatment, patients should avoid driving vehicles or operating complex machinery requiring high concentration and rapid reaction speed.

Method of Administration and Dosage

Hemaxam is administered intravenously (by drip or bolus injection).

The dosage regimen is individual and depends on the clinical situation.

In generalized fibrinolysis: administer at a single dose of 15 mg/kg body weight every 6–8 hours; the infusion rate should be 1 mL/min.

In local fibrinolysis: the recommended dose is 200–500 mg 2–3 times daily.

During prostatectomy or bladder surgery: administer 1 g intraoperatively, followed by 1 g every 8 hours for 3 days, then switch to oral tablet form until macrohematuria resolves.

If there is a high risk of bleeding associated with systemic inflammatory response, the drug is recommended at a dose of 10–11 mg/kg administered 20–30 minutes prior to surgical intervention.

For patients with coagulopathy undergoing tooth extraction: administer the drug at a dose of 10 mg/kg body weight before extraction; after extraction, prescribe oral administration of tranexamic acid tablets.

In case of impaired renal excretory function, dosage adjustment is required:

• When serum creatinine concentration is 120–250 µmol/L: administer 10 mg/kg twice daily;
• When serum creatinin concentration is 250–500 µmol/L: administer 10 mg/kg once daily;
• When serum creatinine concentration is above 500 µmol/L: administer 5 mg/kg once daily.

Children

The maximum single dose should not exceed 10 mg/kg body weight. The maximum daily dose is 20 mg/kg body weight.

Overdose

In case of overdose, nausea, vomiting, and orthostatic hypotension may occur.

Treatment is symptomatic; forced diuresis is indicated. It is necessary to maintain water and electrolyte balance.

Side effects.

Immune system side effects: allergic reactions (rash, itching, urticaria), allergic dermatitis, hypersensitivity reactions, including anaphylaxis.

Gastrointestinal side effects: dyspeptic symptoms (anorexia, nausea, vomiting, heartburn, diarrhea, stomach and intestinal discomfort).

Cardiac side effects: tachycardia, chest pain, arterial or venous embolism, hypotension with or without loss of consciousness (after rapid intravenous injection or, exceptionally, after oral administration).

Eye-related side effects: color vision disturbances, blurred vision.

Blood and lymphatic system side effects: thrombosis or thromboembolism (risk of occurrence is minimal).

Renal side effects: acute cortical necrosis of the kidneys.

General disorders: seizures, dizziness, weakness, drowsiness, malaise.

Shelf life. 3 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C.

Keep out of reach of children.

Incompatibility.

Hemaxam is incompatible with blood products, solutions containing penicillin, hypertensive agents (norepinephrine, deoxyepinephrine hydrochloride), tetracyclines, dipyridamole, and diazepam.

Incompatible with urokinase, except when used as an antidote following urokinase overdose.

Packaging.

5 ml in a polyethylene ampoule. 10 or 50 ampoules per cardboard box.

10 ml in a polyethylene ampoule. 5, 6, or 10 ampoules per cardboard box.

Prescription category. Prescription only.

Manufacturer.

HOLOPACK Verpackungstechnik GmbH (unpacked product, primary packaging, secondary packaging, control).

LLC "FARMASEL" (control, batch release).

Manufacturer's address and place of business.

Bahnhofstrasse 20, 73453 Abtsgmünd-Untergröningen, Germany;

Bahnhofstrasse 18, 74429 Sulzbach-Laufen, Germany.

Tel.: +49 7975 5296

E-mail: [email protected]

Ukraine, 61112, Kharkiv, Traktorobudivnykiv Ave., 94.

Ukraine, 03115, Kyiv, Sviatoshynska St., 34.

Tel.: +38 (095) 282-66-10

E-mail: [email protected]