INSTRUCTION

for medical use of the medicinal product

 

ACEMIK

 

Composition:

active substance: tranexamic acid;

1 film-coated tablet contains tranexamic acid 500 mg;

excipients: microcrystalline cellulose, corn starch, povidone, croscarmellose sodium, stearic acid, colloidal silicon dioxide anhydrous, magnesium stearate;

tablet coating: Opadry White (hydroxypropyl methylcellulose, titanium dioxide (E 171), polyethylene glycol, polysorbate-80).

 

Pharmaceutical form. Film-coated tablets.

Basic physical and chemical properties: white to off white, capsule shaped, film-coated tablets with a break line on one side and 500 embossed on the other.

 

Pharmacotherapeutic group. Antihemorrhagics. Fibrinolysis inhibitors.

ATC code: B02A A02.

 

Pharmacological properties.

Pharmacodynamics.

Tranexamic acid is an antifibrinolytic compound which is a potent competitive inhibitor of the activation of plasminogen to plasmin. At much higher concentrations it is a non-competitive inhibitor of plasmin. The inhibitory effect of tranexamic acid in plasminogen activation by urokinase has been reported to be 6-100 times and by streptokinase 6-40 times greater than that of aminocaproic acid. The antifibrinolytic activity of tranexamic acid is approximately ten times greater than that of aminocaproic acid.

Pharmacokinetics.

Absorption. When tranexamic acid is administered intravenously at a dose of 500 mg, the maximum plasma concentration (C_max) is reached immediately, and then the concentration decreases over 6 hours. Elimination half-life is about 3 hours.

Distribution. Tranexamic acid administered parenterally is distributed in a two compartment model. Tranexamic acid is delivered in the cell compartment and the cerebrospinal fluid with delay. The distribution volume is about 33% of the body mass.

Tranexamic acid crossed the placenta, and may reach 1/100 С_max in the milk of lactating women.

Elimination. Tranexamic acid is excreted in urine as unchanged compound. 90% of the administered dose is excreted by the kidney in the twelve first hours after administration (glomerular excretion without tubular reabsorption).

Following oral administration, 1.13% and 39% of the administered dose were recovered after 3 and 24 hours respectively.

Plasma concentrations are increased in patients with renal insufficiency.

 

Clinical particulars.

Indication.

Haemorrhage or risk of haemorrhage in those with increased fibrinolysis or fibrinogenolysis.

Local fibrinolysis as occurs in the following conditions:

• - prostatectomy and bladder surgery;
• - menorrhagia;
• - epistaxis;
• - conisation of the cervix;
• - traumatic hyphaema.

Hereditary angioneurotic oedema.

Management of dental extraction in haemophiliacs.

 

Contraindications.

• - Hypersensitivity to tranexamic acid and the components of the medicinal product.
• - Severe renal failure because of risk of accumulation.
• - Active thromboembolic disease.
• - History of venous or arterial thrombosis.
• - Fibrinolytic conditions following consumption coagulopathy.
• - History of convulsions.

 

Interaction with other medicinal products and other forms of interaction.

Tranexamic acid will counteract the thrombolytic effect of fibrinolytic preparations.

 

Precautions for use.

In case of haematuria of renal origin (especially in haemophilia), there is a risk of mechanical anuria due to formation of a ureteral clot.

In the long-term treatment of patients with hereditary angioneurotic oedema, regular eye examinations (e.g. visual acuity, slit lamp, intraocular pressure, visual fields) and liver function tests should be performed.

Patients with irregular menstrual bleeding should not use tranexamic acid until the cause of irregular bleeding has been established. If menstrual bleeding is not adequately reduced by tranexamic acid, an alternative treatment should be considered.

Tranexamic acid should be administered with care in patients receiving oral contraceptives because of the increased risk of thrombosis.

Patients with a previous thromboembolic event and a family history of thromboembolic disease (patients with thrombophilia) should use tranexamic acid only if there is a strong medical indication and under strict medical supervision.

The blood levels are increased in patients with renal insufficiency. Therefore a dose reduction is recommended (see section “Method of administration and dosage”).

The use of tranexamic acid in cases of increased fibrinolysis due to disseminated intravascular coagulation is not recommended.

Patients who experience visual disturbance should be withdrawn from treatment.

Clinical experience with tranexamic acid in menorrhagic children under 15 years of age is not available.

Cases of convulsions have been reported in association with tranexamic acid treatment. In cardiac surgery, most of the cases were reported following intravenous injection of tranexamic acid in high doses.

 

Pregnancy and lactation.

Pregnancy

Although there is no evidence from animal studies of a teratogenic effect, the usual caution with use of drugs in pregnancy should be observed.

Tranexamic acid crosses the placenta.

Breast-feeding

Tranexamic acid is excreted into breast milk in a concentration that is approximately 100 times lower than the concentration in the maternal blood. An antifibrinolytic effect in the infant is unlikely.

 

Effects on ability to drive and use machines.

The medicinal product does not affect or has a negligible effect on the ability to drive vehicles or other machinery. When using the medicinal product, you should refrain from driving vehicles or other machinery.

 

Method of administration and dosage.

Method of administration

The medicinal product is intended for oral administration.

Dosage

1. Local fibrinolysis:

The recommended standard dose is 15-25 mg/kg bodyweight (i.e. 2-3 tablets) two to three times daily.

For the indications listed below the following doses may be used:

• – Prostatectomy

Prophylaxis and treatment of haemorrhage in high risk patients should commence per- or post-operatively with an injectable form; thereafter 2 tablets three to four times daily until macroscopic haematuria is no longer present.

• – Menorrhagia

Recommended dosage is 2 tablets 3 times daily as long as needed for up to 4 days. If very heavy menstrual bleeding, dosage may be increased. A total dose of 4 g daily (8 tablets) should not be exceeded. Treatment with tranexamic acid should not be initiated until menstrual bleeding has started.

• – Epistaxis

When repeated bleeding is anticipated oral therapy (2 tablets three times daily) should be administered for 7 days.

• – Cervix conisation

3 tablets three times daily

• – Traumatic hyphaema

2-3 tablets 3 times daily. The dose is based on 25 mg/kg three times a day.

2. Hereditary angioneurotic oedema.

Some patients are aware of the onset of illness; suitable treatment for these patients is intermittently 2-3 tablets two to three times daily for some days. Other patients are treated continuously at this dosage.

3. Haemophilia.

In the management of dental extractions 2-3 tablets every eight hours. The dose is based on 25 mg/kg.

Renal insufficiency

Dose adjustment is required for patients with mild to moderate renal impairment according to plasma creatinine levels:

Serum creatinine	Oral dosage
120-250 μmol/l	15 mg/kg twice a day
250-500 μmol/l	15 mg/kg every 24 hours

Elderly:

No dose reduction is necessary in the absence of renal insufficiency.

Pediatric population.

No clinical experience of tranexamic acid use in children under 15 years of age with menorrhagia is available, so the medicinal product must not be used in this category of patients.

The recommended dose for children is 25 mg/kg. There are limited data on the efficacy, dosage and safety of tranexamic acid in children.

 

Overdose.

Symptoms: nausea, vomiting, orthostatic hypotension, arterial hypotension, dizziness, headache, convulsions. There is a risk of thrombosis in predisposed individuals.

Treatment: initiate vomiting, stomach lavage, charcoal therapy. Maintain a high fluid intake to promote renal excretion. Symptomatic treatment and, if necessary, anticoagulant therapy should be used.

 

Adverse reactions.

Adverse reactions are classified according to their frequency and effect on organs or organ systems. The following adverse reactions have been reported. They are classified according to frequency as follows: very common (≥1/10); common (≥1/100 - < 1/10); uncommon (≥1/1000 - < 1/100); rare (≥1/10,000 - < 1/1,000); very rare (< 1/10,000); not known (cannot be estimated from available data).

Immune system disorders:

hypersensitivity reactions including anaphylaxis.

Immune system disorders:

Very rare: hypersensitivity, including anaphylaxis.

Eye disorders:

Rare: color vision disorders, vein/artery retinal occlusion.

Vascular disorders:                   

Rare: thromboembolism.

Very rare: arterial or venous thrombosis of any localization.

Digestive tract disorders:

Very rare: nausea, vomiting, and diarrhea, all of which disappear with a reduced dose.

Skin and subcutaneous tissue disorders:

Rare: allergic skin reactions.

Nervous system disorders:

Not known: convulsions, particularly as a result of improper use (see section “Contraindications”, “Precautions for use”).

 

Reporting of suspected adverse reactions

Reporting adverse reactions after the registration of a medicinal product is of great importance. It enables the monitoring of the benefit/risk ratio associated with the use of the medicinal product. Healthcare professionals, pharmacists, as well as patients or their legal representatives, should report all suspected adverse reactions and cases of lack of efficacy of the medicinal product via the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

 

Shelf-life. 2 years.

 

Storage conditions.  

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

Keep out of reach of children.

 

Packaging.

10 tablets in a blister. 1 blister in a carton.

 

Terms of dispensing. On prescription.

 

 

Date of last update.

18.05.2023