Vidanol®

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT VYDANOL® (VIDANOL®)

Composition:

Active ingredient: tranexamic acid;

One tablet contains 500 mg of tranexamic acid;

Excipients: microcrystalline cellulose, low-substituted hydroxypropylcellulose, povidone K30, sodium croscarmellose, colloidal anhydrous silicon dioxide, talc, magnesium stearate, Colorcoat FC4S white coating: hypromellose, diethyl phthalate, hydrogenated castor oil powder, stearic acid, talc, titanium dioxide (E 171).

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties: white, round, biconvex, film-coated tablets, smooth on both sides.

Pharmacotherapeutic group.

Antihemorrhagics. Fibrinolysis inhibitors. ATC code B02A A02.

Pharmacological Properties.

Pharmacodynamics.

Tranexamic acid is an antifibrinolytic agent that acts as a potent competitive inhibitor of the conversion of plasminogen to plasmin. At high concentrations, it acts as a non-competitive inhibitor of plasmin. It has been shown that the inhibitory effect of tranexamic acid on plasminogen activation by urokinase is 6–100 times greater, and by streptokinase is 6–40 times greater, than that of aminocaproic acid. The antifibrinolytic activity of tranexamic acid is approximately 10 times higher than that of aminocaproic acid. Additionally, by suppressing the formation of kinins and other active peptides involved in allergic and inflammatory reactions, tranexamic acid exerts antiallergic and anti-inflammatory effects.

Pharmacokinetics.

Absorption. After intravenous administration of tranexamic acid at a dose of 500 mg, 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. After parenteral administration, tranexamic acid is distributed in two directions: it is slowly absorbed into the 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. About 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 concentrations of tranexamic acid are 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 insufficiency (due to the risk of accumulation).
• Acute 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 medicinal products.

Special precautions for use

In the event of renal origin hematuria (especially in patients with hemophilia), there is a risk of obstruction of the lower urinary tract due to blood clot formation. If left untreated, such obstruction may lead to serious complications, including renal failure, urinary tract infection, hydronephrosis, and anuria. Therefore, patients with hematuria or at risk of hematuria originating from the upper urinary tract should be carefully monitored.

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 recommended.

Female patients with irregular menstrual bleeding should not use tranexamic acid until the underlying 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 due to an increased risk of thrombosis.

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

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

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

If visual disturbances occur, treatment should be discontinued.

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 treatment with tranexamic acid. Most of these cases occurred in cardio-surgical settings following high-dose intravenous (i.v.) administration of tranexamic acid.

Excipients

This medicinal product contains hydrogenated castor oil, which may cause gastrointestinal discomfort and diarrhea. This medicinal product contains less than 1 mmol (23 mg) of sodium per dose, i.e., essentially "sodium-free".

Use during pregnancy or breastfeeding

Pregnancy

Although preclinical studies in animals have not shown teratogenic effects of tranexamic acid on fetal development, it is recommended to follow general guidelines for the use of medicinal products during pregnancy. Tranexamic acid crosses the placenta.

Breastfeeding

Tranexamic acid is excreted into breast milk at a concentration approximately 1/100 of the maternal plasma concentration. An antifibrinolytic effect in the infant is unlikely.

Effect on ability to drive and use machines

Tranexamic acid has no or negligible influence on the ability to drive vehicles or operate machinery. However, visual disturbances may occur after administration of tranexamic acid.

Administration and Dosage.

For oral administration in adults. The drug is taken independently of food intake.

	Local fibrinolysis: the recommended standard dose is 15–25 mg/kg body weight (i.e. 2–3 tablets of 500 mg) 2–3 times daily. The following dosages may be used for the indications listed below:
	-	Prostatectomy: to prevent and treat hemorrhages in patients at increased risk, tranexamic acid should be administered by injection before or after surgery. Afterwards, tablets should be given at a dose of 1 g (2 tablets of 500 mg) 3–4 times daily until macroscopic hematuria disappears.
	-	Menorrhagia: the recommended dose is 1 g (2 tablets of 500 mg) 3 times daily, for no more than 4 days. In case of prolonged menstrual bleeding, the dose may be increased, not exceeding the maximum daily dose of 4 g (8 tablets of 500 mg). Treatment should not be initiated before the onset of menstrual bleeding.
	-	Nosebleeds: for recurrent episodes, 1 g (2 tablets of 500 mg) 3 times daily for 7 days.
	-	Cervical conization: 1.5 g (3 tablets of 500 mg) 3 times daily.
	-	Post-traumatic hyphema: 1–1.5 g (2–3 tablets of 500 mg) 3 times daily. The dose is 25 mg/kg 3 times daily.
	Hereditary angioedema: some patients familiar with the course of disease exacerbations usually require 1–1.5 g (2–3 tablets of 500 mg) 2–3 times daily for several days. Other patients should take the medication at the same dose over a prolonged period, depending on the disease course.
	Tooth extraction in patients with hemophilia: 25 mg/kg (2–3 tablets of 500 mg) every 8 hours.

Patients with renal impairment.

Dosage adjustment is required for patients with mild to moderate renal impairment based on plasma creatinine levels.

Serum creatinine	Oral dose
120–249 µmol/L	15 mg/kg twice daily
250–500 µmol/L	15 mg/kg every 24 hours

Elderly patients

If there are no impairments in renal excretory function, dose adjustment is not required.

Children

The medicinal product is intended for use in adult patients.

There is no clinical experience with the use of tranexamic acid in children and adolescents under 15 years of age.

The dose for this patient group should be calculated according to body weight at 25 mg/kg per dose. However, data on dosing, efficacy, and safety for the specified indications are limited.

Overdose.

Symptoms: nausea, diarrhea, vomiting, abdominal pain, orthostatic symptoms and/or hypotension, dizziness, headache, and seizures.

Treatment: induce vomiting, gastric lavage, administer activated charcoal. It is necessary to consume large amounts of fluid to promote renal excretion. There is a risk of thrombosis in predisposed individuals. Symptomatic treatment should be administered and, if necessary, anticoagulant therapy.

Adverse Reactions

The adverse reactions listed below are classified according to their frequency and impact on organs or body systems. Frequency is defined as follows: very common (≥1/10), common (≥1/100 and <1/10), uncommon (≥1/1,000 and <1/100), rare (≥1/10,000 and <1/1,000), very rare (<1/10,000), including isolated case reports, and not known (cannot be estimated from available data).

Immune system disorders:

Very rare: hypersensitivity reactions, including anaphylaxis.

Eye disorders:

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

Vascular disorders:

Rare: thromboembolic complications.

Very rare: arterial or venous thrombosis of any localization.

Gastrointestinal disorders:

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

Skin and subcutaneous tissue disorders:

Rare: allergic skin reactions.

Nervous system disorders:

Frequency not known: seizures, especially in cases of improper use (see sections "Contraindications" and "Special precautions for use").

Reporting suspected adverse reactions.

Reporting suspected adverse reactions after marketing authorization of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals and patients, as well as patients' legal representatives, are encouraged to report any suspected adverse reactions and lack of efficacy through the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

Shelf life. 3 years.

Storage conditions.

Store at temperatures not exceeding 25 °C.

Keep out of reach and sight of children.

Packaging.

10 tablets per blister; 3 or 6 blisters per cardboard pack.

Prescription status. Prescription only.

Manufacturer.

GLF PHARM LTD LLC.

Manufacturer's address and location of business activity.

54 Davydovskoho Hryhoriia St., Sumy, Sumy Oblast, 40020, Ukraine.

INSTRUCTIONS

for medical use of the medicinal product

VIDANOL®

(VIDANOL®)

Composition:

Active ingredient: tranexamic acid (tranexamic acid);

1 tablet contains 500 mg of tranexamic acid;

Excipients: microcrystalline cellulose, low-substituted hydroxypropylcellulose, povidone K30, sodium croscarmellose, colloidal anhydrous silicon dioxide, talc, magnesium stearate, Colorcoat FC4S white coating: hydroxypropylmethylcellulose, diethyl phthalate, hydrogenated castor oil powder, stearic acid, talc, titanium dioxide (E 171).

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties: white, round, biconvex, film-coated tablets, smooth on both sides.

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 the conversion of plasminogen to plasmin. At high concentrations, it acts as a non-competitive inhibitor of plasmin. The inhibitory effect of tranexamic acid on plasminogen activation by urokinase is reported to be 6–100 times greater, and by streptokinase 6–40 times greater, than that of aminocaproic acid. The antifibrinolytic activity of tranexamic acid is approximately 10 times higher than that of aminocaproic acid. Additionally, by suppressing the formation of kinins and other active peptides involved in allergic and inflammatory reactions, tranexamic acid exerts anti-allergic and anti-inflammatory effects.

Pharmacokinetics.

Absorption. Following intravenous administration of 500 mg tranexamic acid, the maximum plasma concentration (Cmax) is achieved immediately, after which the concentration decreases over 6 hours. The elimination half-life is approximately 3 hours.

Distribution. After parenteral administration, tranexamic acid is distributed in two directions: it is slowly absorbed into the 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 the urine. About 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 concentrations of tranexamic acid are 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 angioedema.

Tooth extraction in patients with hemophilia.

Contraindications.

• Hypersensitivity to tranexamic acid or to any of the excipients.
• Severe renal insufficiency (due to risk of accumulation).
• Acute 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 interactions.

Tranexamic acid antagonizes thrombolytic therapy with fibrinolytic medicinal products.

Special precautions for use.

In cases of renal origin hematuria (especially in hemophilia), there is a risk of obstruction of the lower urinary tract due to blood clot formation. If left untreated, such obstruction may lead to serious complications, including renal failure, urinary tract infection, hydronephrosis, and anuria. Therefore, patients with hematuria or at risk of hematuria originating from the upper urinary tract should be closely monitored.

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

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

Tranexamic acid should be used with caution in patients taking oral contraceptives due to an increased risk of thrombosis.

Patients with a personal or family history of thromboembolic complications (patients with thrombophilia) should use tranexamic acid only when there is a clear medical indication and under strict medical supervision.

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

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

If visual disturbances occur, treatment should be discontinued.

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 treatment with tranexamic acid. Most of these cases occurred in cardiac surgery following high-dose intravenous (i.v.) administration of tranexamic acid.

Excipients

The medicinal product contains hydrogenated castor oil, which may cause gastrointestinal disturbances and diarrhea. This medicinal product contains less than 1 mmol (23 mg) of sodium per dose, i.e., it is practically sodium-free.

Use during pregnancy or breastfeeding.

Pregnancy.

Although preclinical studies in animals have not shown teratogenic effects of tranexamic acid on fetal development, it is recommended to follow general guidelines for the use of medicinal products during pregnancy. Tranexamic acid crosses the placenta.

Breastfeeding.

Tranexamic acid passes into breast milk at a concentration approximately 1/100 of the maternal plasma concentration. An antifibrinolytic effect in the infant is unlikely.

Effect on ability to drive and use machines.

Tranexamic acid has no effect or has a negligible effect on the ability to drive vehicles or operate machinery. Visual disturbances may occur after administration of tranexamic acid.

Administration and Dosage.

For adults, the medicinal product is administered orally. It is taken regardless of food intake.

	Local fibrinolysis: the recommended standard dose is 15–25 mg/kg body weight (i.e. 2–3 tablets of 500 mg) 2–3 times daily. The following dosages may be used for the indications listed below:
	-	Prostatectomy: to prevent and treat hemorrhage in patients at increased risk, tranexamic acid is administered by injection before or after surgery. Afterwards, tablets are used, 1 g (2 tablets of 500 mg) 3–4 times daily until macroscopic hematuria disappears.
	-	Menorrhagia: the recommended dose is 1 g (2 tablets of 500 mg) 3 times daily, for no more than 4 days. In case of prolonged menstrual bleeding, the dose may be increased, not exceeding the maximum daily dose of 4 g (8 tablets of 500 mg). Treatment should not be initiated before the onset of menstrual bleeding.
	-	Nosebleeds: for recurrent episodes, 1 g (2 tablets of 500 mg) 3 times daily for 7 days.
	-	Cervical conization: 1.5 g (3 tablets of 500 mg) 3 times daily.
	-	Post-traumatic hyphema: 1–1.5 g (2–3 tablets of 500 mg) 3 times daily. The dose is 25 mg/kg 3 times daily.
	Hereditary angioedema: some patients familiar with the course of disease exacerbations usually require 1–1.5 g (2–3 tablets of 500 mg) 2–3 times daily for several days. Other patients should take the medication at the same dose over a prolonged period, depending on the disease course.
	Tooth extraction in patients with hemophilia: 25 mg/kg (2–3 tablets of 500 mg) every 8 hours.

Patients with renal impairment.

Dosage adjustment is required for patients with mild and moderate renal impairment based on plasma creatinine levels.

Serum creatinine	Oral dose
120–249 µmol/L	15 mg/kg twice daily
250–500 µmol/L	15 mg/kg every 24 hours

Elderly patients

If there are no impairments in renal excretory function, dose adjustment is not required.

Children

The medicinal product is intended for use in adult patients.

There is no clinical experience with the use of tranexamic acid in children and adolescents under 15 years of age.

The dose for this patient group should be calculated according to body weight at 25 mg/kg per dose. However, data on dosing, efficacy, and safety for the specified indications are limited.

Overdose.

Symptoms: nausea, diarrhea, vomiting, abdominal pain, orthostatic symptoms and/or hypotension, dizziness, headache, and seizures.

Treatment: induce vomiting, gastric lavage, administration of activated charcoal. It is necessary to consume large amounts of fluid to promote renal excretion. There is a risk of thrombosis in predisposed individuals. Symptomatic treatment should be applied and, if necessary, anticoagulant therapy.

Adverse Reactions

The adverse reactions listed below are classified according to their frequency and effects on organs or body systems. Frequency is defined as: very common (≥1/10), common (≥1/100 and <1/10), uncommon (≥1/1,000 and <1/100), rare (≥1/10,000 and <1/1,000), very rare (<1/10,000), including isolated case reports, and not known (cannot be estimated from available data).

Immune system disorders:

Very rare: hypersensitivity reactions, including anaphylaxis.

Eye disorders:

Rare: disturbances in color vision, retinal vein/artery occlusion.

Vascular disorders:

Rare: thromboembolic complications.

Very rare: arterial or venous thrombosis at any site.

Gastrointestinal disorders:

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

Skin and subcutaneous tissue disorders:

Rare: allergic skin reactions.

Nervous system disorders:

Frequency not known: seizures, particularly in cases of incorrect use (see sections "Contraindications" and "Special Warnings and Precautions for Use").

Reporting of suspected adverse reactions.

Reporting suspected adverse reactions after medicine registration is important. It allows continuous monitoring of the benefit-risk balance of the medicine. Healthcare and pharmaceutical professionals, as well as patients or their legal representatives, are encouraged to report any suspected adverse reactions and lack of efficacy through the Automated Pharmacovigilance Information System at: https://aisf.dec.gov.ua.

Shelf life. 3 years.

Storage conditions.

Store at a temperature not exceeding 25 °C.

Keep out of reach and sight of children.

Packaging.

10 tablets per blister; 3 or 6 blisters per cardboard box.

Prescription status. Prescription only.

Manufacturer.

KUSUM HEALTHCARE PVT LTD.

Manufacturer's address and location of business activity.

SP-289 (A), RIICO Industrial Area, Chopanki, Bhiwadi, Dist. Alwar (Rajasthan), India.