Acemik

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT ACEDIK (ACEMIK)

Composition:

Active substance: tranexamic acid;

One film-coated tablet contains 500 mg of tranexamic acid;

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

Coating of the tablet: Opadry White (hydroxypropylmethylcellulose, titanium dioxide (E 171), polyethylene glycol, polysorbate 80).

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties: film-coated tablets, white or almost white, capsule-shaped, with a break line on one side and embossing "500" on the other.

Pharmacotherapeutic group. Antihemorrhagic agents. Fibrinolysis inhibitors.

ATC code B02A A02.

Pharmacological properties.

Pharmacodynamics.

Tranexamic acid is an antifibrinolytic agent that acts as a potent competitive inhibitor of plasminogen activation to plasmin. At significantly higher concentrations, it acts as a non-competitive inhibitor of plasmin. The inhibitory effect of tranexamic acid on plasminogen activation by urokinase is 6–100 times greater, and by streptokinase – 6–40 times greater, compared to the inhibitory effect of aminocaproic acid. The antifibrinolytic activity of tranexamic acid is approximately 10 times higher than that of aminocaproic acid.

Pharmacokinetics.

Absorption. After intravenous administration of 500 mg of tranexamic acid, maximum plasma concentration (Cmax) is achieved immediately, followed by a decline in concentration over 6 hours. The elimination half-life is approximately 3 hours.

Distribution. Parenterally administered tranexamic acid distributes in two directions: slowly into cerebrospinal fluid and into cells. The volume of distribution is approximately 33% of body weight.

Tranexamic acid can cross the placental barrier. In breast milk of lactating women, its concentration may reach about 1/100 of Cmax.

Elimination. Tranexamic acid is excreted unchanged in urine. 90% of the administered dose is excreted by the kidneys within the first 12 hours after administration (glomerular filtration without tubular reabsorption).

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

In patients with renal insufficiency, plasma concentration is increased.

Clinical characteristics.

Indications.

Short-term treatment of bleeding or risk of bleeding due to enhanced fibrinolysis or fibrinogenolysis.

Local fibrinolysis observed in the following conditions:

• prostatectomy or interventions on the urinary bladder;
• menorrhagia;
• epistaxis;
• cervical conization;
• post-traumatic hyphema.

Hereditary angioneurotic edema.

Tooth extraction in patients with hemophilia.

Contraindications.

• Hypersensitivity to tranexamic acid or to any of the excipients.
• Severe renal impairment due to the risk of drug accumulation.
• Active thromboembolic disorders.
• History of arterial or venous thrombosis.
• Fibrinolytic states due to consumption coagulopathy.
• History of seizures.

Interaction with other medicinal products and other forms of interaction.

Tranexamic acid antagonizes thrombolytic therapy with fibrinolytic agents.

Special precautions for use.

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

For patients with hereditary angioedema undergoing long-term therapy, regular monitoring of vision (e.g., visual acuity, visual fields, intraocular pressure, fundus oculi) and liver function (liver function tests) is required.

Female patients with irregular menstrual bleeding should not use tranexamic acid until the cause of bleeding has been established. If treatment with tranexamic acid does not reduce the intensity of menstrual bleeding, alternative treatment options should be considered.

Tranexamic acid should be used with caution in patients taking oral contraceptives, as this increases the risk of thrombosis.

Patients with a history of thromboembolic disease or a family history of thromboembolic disorders (patients with thrombophilia) should use tranexamic acid only when clearly indicated and under strict medical supervision.

Since tranexamic acid levels may increase in patients with renal impairment, dose reduction is recommended (see section "Method of administration and dosage").

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

Treatment should be discontinued in patients experiencing visual disturbances.

There is no clinical experience with the use of tranexamic acid for the treatment of menorrhagia in children under 15 years of age.

Seizures have been reported during the use of tranexamic acid. Most cases occurred in cardiac surgery following high-dose intravenous administration of tranexamic acid.

Use during pregnancy or breastfeeding.

Pregnancy.

Despite the absence of evidence for teratogenic effects of tranexamic acid in animal studies, caution should be exercised when using the drug during pregnancy.

Tranexamic acid crosses the placenta.

Breastfeeding.

Tranexamic acid is excreted in breast milk at concentrations approximately 100 times lower than those in maternal blood. An antifibrinolytic effect in infants is unlikely.

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

The medicinal product has no effect or has a negligible effect on the ability to drive vehicles or operate machinery. However, during treatment with this medicinal product, patients should refrain from driving vehicles or operating machinery.

Method of Administration and Dosage

Method of Administration

The medicinal product is intended for oral (internal) use.

Dosage

1. Local fibrinolysis:

The recommended standard dose is 15–25 mg/kg body weight (i.e. 2–3 tablets) 2–3 times daily.

For the following indications, the following dosage regimens may be used:

• Prostatectomy

For prophylaxis and treatment of hemorrhage in patients at increased risk, prior to or following surgery, tranexamic acid is initially administered by injection; subsequently, the tablet form is prescribed as 2 tablets 3–4 times daily until macroscopic hematuria disappears.

• Menorrhagia

The recommended dose is 2 tablets 3 times daily for 4 days. In cases of prolonged menstrual bleeding, the dose may be increased. The total daily dose should not exceed 4 g (8 tablets of 500 mg per day). Treatment should not be initiated before the onset of menstrual bleeding.

• Epistaxis (nosebleeds)

If recurrent bleeding is expected, oral treatment (2 tablets 3 times daily) should be administered for 7 days.

• Cervical conization

Administer 3 tablets 3 times daily.

• Post-traumatic hyphema

Administer 2–3 tablets 3 times daily. The dose is 25 mg/kg 3 times daily.

2. Hereditary angioedema

Some patients are aware of the onset of exacerbations; for these patients, appropriate treatment consists of intermittent administration of 2–3 tablets 2–3 times daily for several days. Other patients should take the drug at the same dosage over a prolonged period.

3. Dental extraction in patients with hemophilia

For dental extractions, the recommended dose is 2–3 tablets every 8 hours. The dose is 25 mg/kg.

Renal impairment

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

Elderly patients.

Dose reduction is not necessary in the absence of renal impairment.

Children.

There is no clinical experience with the use of tranexamic acid in children under 15 years of age with menorrhagia; therefore, the medicinal product should not be used in this patient population.

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

Overdose.

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

Treatment: induce vomiting, gastric lavage, administer activated charcoal. It is essential to maintain high fluid intake to promote renal excretion. Symptomatic treatment should be provided, and anticoagulant therapy should be administered if necessary.

Side effects

Side effects are classified according to their frequency and impact on organs or body systems. The adverse reactions listed below have been reported and are categorized by frequency as follows: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000); frequency not known (cannot be estimated from available data).

Immune system:

Very rare: hypersensitivity reactions, including anaphylaxis.

Eye disorders:

Rare: colour vision disturbances, retinal vein/artery occlusion.

Vascular disorders:

Rare: thromboembolism.

Very rare: arterial or venous thrombosis at any site.

Gastrointestinal disorders:

Very rare: nausea, vomiting, and diarrhoea, which resolve upon dose reduction.

Skin and subcutaneous tissue disorders:

Rare: allergic skin reactions.

Nervous system disorders:

Frequency not known: seizures, particularly due to incorrect use (see section "Contraindications", "Special warnings and precautions for use").

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after medicinal product authorization is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare and pharmacy professionals, as well as patients or their legal representatives, should report any suspected adverse reactions and 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 a temperature not exceeding 25°C.

Keep out of reach and sight of children.

Packaging.

10 tablets in a blister. 1 blister per box.

Prescription status. Prescription only.

Manufacturer: Artura Pharmaceuticals Pvt. Ltd.

Manufacturer's address and location of operations.

1505 Portia Road, Sri City SEZ, Sathyavedu Mandal, Chittoor District – 517 588, Andhra Pradesh, India.

Marketing Authorization Holder: Ananta Medicare Ltd.

Address of Marketing Authorization Holder:

Suite 1, 2 Station Court, Imperial Wharf, Townmead Road, Fulham, London, United Kingdom