Etamsylate-darnitsa

INSTRUCTIONS for medical use of the medicinal product Etamsylate-Darnitsa (Etamsylate-Darnitsa)

Composition:

Active substance: etamsylate;

1 ml of solution contains 125 mg of etamsylate;

Excipients: sodium sulfite anhydrous (E 221), edetate disodium, water for injections.

Pharmaceutical form. Injection solution.

Main physicochemical properties: clear, colorless or slightly yellowish liquid.

Pharmacotherapeutic group. Antihemorrhagic agents. Other systemic hemostatic agents. ATC code B02B X01.

Pharmacological properties.

Pharmacodynamics.

Etamsylate-Darnytsia is a medication intended for prevention and cessation of bleeding. It affects the first stage of the hemostasis mechanism (interaction between endothelium and platelets). The drug enhances platelet adhesiveness, normalizes capillary wall resistance thereby reducing their permeability, and inhibits biosynthesis of prostaglandins which cause platelet disaggregation, vasodilation, and increased capillary permeability. As a result, bleeding time is significantly reduced and blood loss is diminished.

Pharmacokinetics.

After intramuscular administration, the drug rapidly enters systemic circulation. It binds to plasma proteins and is partially adsorbed onto the surface of blood formed elements. Following intramuscular injection of 250 mg (2 mL) of Etamsylate-Darnytsia, maximum blood concentration is reached within 1–2 hours.

After intravenous administration, the hemostatic effect begins within 5–15 minutes, reaching its maximum within 1 hour. The drug remains effective for 4–6 hours, after which the effect gradually subsides. Following intravenous administration of 500 mg of Etamsylate-Darnytsia, peak plasma concentration of 50 μg/mL is achieved within 10 minutes.

Approximately 72% of the administered dose is excreted unchanged in urine within the first 24 hours. The plasma half-life of etamsylate is approximately 2 hours. The drug crosses the placental barrier and is excreted into breast milk.

Clinical characteristics.

Indications.

Prevention and control of hemorrhages in superficial and internal capillaries of various etiologies, especially when bleeding is caused by endothelial damage, including:

• prevention and treatment of bleeding during and after surgical procedures in otorhinolaryngology, gynecology, obstetrics, urology, dentistry, ophthalmology, and plastic surgery;
• prevention and treatment of capillary hemorrhages of various etiologies and localizations: hematuria, metrorrhagia, primary hypermenorrhea, hypermenorrhea in women with intrauterine contraceptive devices, epistaxis, gingival bleeding;
• neonatology: prevention of periventricular hemorrhage in premature infants.

Contraindications.

Hypersensitivity to etamsylate or to any other ingredient of the medicinal product; bronchial asthma; thrombosis; thromboembolism; acute porphyria; increased blood coagulation; bleeding due to anticoagulant overdose; hemoblastosis (lymphatic and myeloid leukemia, osteosarcoma) in children.

Interaction with other medicinal products and other forms of interactions.

Administration at a dose of 10 mg/kg given 1 hour before dextran prevents dextran's anti-aggregatory effect. Administration after dextran does not exhibit hemostatic activity.

The medicinal product may be used concomitantly with other hemostatic agents.

The contents of the ampoule must not be mixed with other medicinal products in the same syringe.

If etamsylate solution is mixed with 0.9% sodium chloride solution, it must be used immediately.

Thiamine (vitamin B1) is inactivated by sulfite present in Etamsylate-Darnytsia solution.

Special precautions for use

Before starting treatment, other causes of bleeding must be ruled out. If etamsylate is used to reduce excessive and/or prolonged menstrual bleeding and no improvement is observed, possible pathological causes (e.g. presence of uterine fibroids) should be excluded.

Use with caution in patients with a history of thrombosis or thromboembolism.

Due to the risk of decreased arterial pressure during parenteral administration, the drug should be used cautiously in patients with unstable blood pressure or hypotension.

If fever develops in a patient during treatment, the drug should be discontinued.

In cases where the patient's condition requires dextran infusion, Etamsylate-Darnytsia should be administered prior to dextran infusion.

The drug is ineffective in cases of reduced platelet count.

In hemorrhagic complications associated with anticoagulant overdose, specific antidotes are recommended.

Use of etamsylate in patients with impaired coagulation parameters is possible, but should be supplemented by administration of medicinal products that correct the identified deficiency or defect in coagulation factors.

The use of the drug is contraindicated if the color of the injection solution changes.

Etamsylate-Darnytsia solution contains the excipient anhydrous sodium sulfite (E 221). In sensitive patients, sulfites may cause hypersensitivity reactions and bronchospasm. Isolated cases of anaphylactic shock and life-threatening asthma attacks have been reported. Increased sensitivity to sulfites is more commonly observed in patients with bronchial asthma.

If allergic reactions or fever develop in a patient during treatment, the drug should be discontinued immediately and the physician should be notified, as this may be a sign of hypersensitivity.

Use in patients with renal impairment

The safety and efficacy of etamsylate have not been studied in patients with renal impairment. Since etamsylate is almost entirely excreted by the kidneys, the dose of the drug should be reduced in cases of renal insufficiency.

Laboratory tests

At therapeutic doses, etamsylate may reduce creatinine measurement test values.

Use during pregnancy or breastfeeding

There are no reliable data on the effect of the drug on the fetus during pregnancy. The drug is contraindicated during the \I\ trimester of pregnancy. In the \II\ and \III\ trimesters of pregnancy, the drug may be used only if the benefit to the mother outweighs the risk to the fetus.

Breastfeeding should be discontinued during treatment with this drug.

Ability to influence reaction rate while driving or operating machinery

During treatment, driving and performing other potentially hazardous activities requiring increased attention and psychomotor reaction speed are not recommended.

Method of administration and dosage.

The medicinal product should be administered intravenously (slowly) or intramuscularly.

The daily dose of the medicinal product for adults is 10–20 mg/kg body weight, administered in 3–4 divided doses (in most cases, the contents of 1–2 ampoules are administered 3–4 times daily). The daily dose for children is 5–10 mg/kg body weight.

Surgical interventions: 1 hour before surgery, administer the contents of 1–2 ampoules intravenously or intramuscularly. During surgery, administer the contents of 1–2 ampoules intravenously; this dose may be repeated if necessary. After surgery, administer the contents of 1–2 ampoules every 4–6 hours until the risk of bleeding has subsided.

Neonatology: the medicinal product should be administered intramuscularly or intravenously at a dose of 12.5 mg/kg body weight (0.1 ml = 12.5 mg). Treatment should be initiated within the first 2 hours after birth. Administer the medicinal product every 6 hours for 4 days, up to a total dose of 200 mg/kg.

Etamsylate-Darnitsya can be used locally (e.g. in skin grafting, tooth extraction) using a sterile gauze pad moistened with the medicinal product.

Concomitant use of the oral form of the medicinal product with parenteral administration is possible.

Hepatic and renal impairment. There are insufficient clinical data to provide dosage recommendations; therefore, the medicinal product should be used with caution in such patients.

Children.

The medicinal product is contraindicated in children with hemoblastosis (lymphoid and myeloid leukemia, osteosarcoma).

Overdose.

There have been no reported cases of overdose to date. Overdose may result in an intensification of known adverse effects.

Treatment: symptomatic.

Adverse reactions.

Respiratory, thoracic, mediastinal system: bronchospasm.

Gastrointestinal system: nausea, vomiting, diarrhea, abdominal pain.

Metabolism and nutritional disorders: very rare – acute porphyria.

Nervous system: rare – headache, dizziness, hot flushes, paresthesia of lower limbs.

Cardiovascular system: very rare – thromboembolism, arterial hypotension, decreased tissue perfusion which spontaneously resolves after some time.

Blood and lymphatic system: agranulocytosis, neutropenia, thrombocytopenia.

Immune system: hypersensitivity reactions, including anaphylactic shock (frequency not known), urticaria, exacerbation of bronchial asthma attacks in asthmatic patients, pruritus, rash; angioneurotic edema has been reported.

Skin and subcutaneous tissue disorders: facial skin redness.

Musculoskeletal and connective tissue disorders: rare – back pain, arthralgia.

General disorders and administration site conditions: asthenia, fever, increased body temperature, pruritus, redness.

All adverse effects are mild and transient.

In children treated with etamsylate for prevention of bleeding in acute lymphoblastic and myeloid leukemia, severe leukopenia was observed more frequently.

Shelf life. 3 years.

Freshly prepared infusion solutions should not be stored for prolonged periods and must be used immediately after preparation.

Storage conditions.

Store in original packaging at a temperature not exceeding 25 °C. Do not freeze. Keep out of reach of children.

Incompatibility.

Etamsylate solution is incompatible with sodium hydrocarbonate and sodium lactate solutions. It is pharmaceutically incompatible (in the same syringe) with other medicinal products. Interaction with thiamine has been described, leading to alteration of the active substance.

Packaging.

2 ml in an ampoule; 5 ampoules in a blister pack, 2 blister packs in a carton.

Prescription category. Prescription only.

Manufacturer. JSC "Pharmaceutical Company "Darnytsia".

Manufacturer's address and place of business.

13, Boryspylska Street, Kyiv, 02093, Ukraine.