DITSINON

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT DICYNONE

Composition:

Active substance: etamsylate;

1 ampoule (2 ml of solution) contains 250 mg of etamsylate;

Excipients: sodium metabisulfite (E 223), sodium bicarbonate, water for injections.

Pharmaceutical form. Solution for injection.

Main physicochemical characteristics: colorless clear solution, practically free from visible particles.

Pharmacotherapeutic group.

Antihemorrhagic agents. Other systemic hemostatic agents.

ATC code B02B X01.

Pharmacological Properties.

Pharmacodynamics.

Ethamsylate is an agent for preventing and stopping bleeding. It affects the first stage of the hemostasis mechanism (interaction between endothelium and platelets). Dicynone increases platelet adhesiveness, normalizes capillary wall resistance, thereby reducing their permeability, and inhibits the biosynthesis of prostaglandins that cause platelet disaggregation, vasodilation, and increased capillary permeability. As a result, bleeding time is significantly reduced, and blood loss decreases.

Pharmacokinetics.

After intravenous administration of the drug, the hemostatic effect appears within 5–15 minutes, reaching its maximum within 1 hour. Maximum plasma concentration of ethamsylate is achieved within 1 hour after intravenous or intramuscular administration of 500 mg of Dicynone and amounts to 30–50 mcg/mL. Approximately 90% of the drug binds to plasma proteins.

Approximately 72% of the administered dose is excreted unchanged in urine within the first 24 hours. The plasma half-life of ethamsylate is approximately 2 hours. Ethamsylate crosses the placental barrier. It is unknown whether ethamsylate passes 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 drug (especially to sodium metabisulfite); bronchial asthma; acute porphyria; increased blood coagulation, thrombosis, thromboembolism; hemoblastosis (lymphatic and myeloid leukemia, osteosarcoma) in children.

Interaction with other medicinal products and other forms of interaction.

Thiamine (vitamin B1) is inactivated by sulfite present in the Dicynone solution.

Administration of etamsylate one hour before infusion of dextrans (e.g., reopolyglucin) prevents their anti-aggregatory effect; when administered after dextrans, etamsylate does not exert hemostatic action.

The drug may be used concomitantly with other hemostatic agents.

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

Special precautions for use

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

The drug should be used with caution in patients with a history of thrombosis or thromboembolism.

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

If a patient requires dextran infusion, etamsylate should be administered prior to the infusion of dextran.

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

Dicynone solution contains sodium metabisulfite (E 223) as an antioxidant excipient. Sulfites may cause allergic reactions, nausea, and diarrhea in sensitive individuals. There have been isolated reports of anaphylactic shock and life-threatening asthma attacks. Hypersensitivity to sulfites is more commonly observed in patients with bronchial asthma.

If allergic reactions or high fever occur, treatment should be discontinued immediately and a physician should be notified, as these may be signs 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 completely excreted by the kidneys, the dose should be reduced in cases of renal insufficiency.

Laboratory tests.

At therapeutic doses, etamsylate may reduce creatinine levels in laboratory tests.

Use during pregnancy or breastfeeding.

There are no reliable data on the effects of Dicynone on the fetus; therefore, the drug is contraindicated during the first trimester of pregnancy. In the second and third trimesters, the drug may be used only if the benefit to the mother outweighs the potential risk to the fetus.

Breastfeeding should be discontinued during treatment with the drug.

Ability to influence reaction rate while driving or operating machinery.

The drug does not impair reaction speed; however, dizziness may occur during treatment, which should be taken into account when driving or operating machinery.

Method of Administration and Dosage

The drug should be administered intravenously (slowly) or intramuscularly. The optimal daily dose for adults is 10–20 mg/kg body weight, given 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 half the adult dose.

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: administer the drug intramuscularly at a dose of 10 mg/kg body weight (0.1 ml = 12.5 mg). Treatment should begin within the first 2 hours after birth. Subsequently, administer the drug every 6 hours for 4 days, up to a total dose of 200 mg/kg.

Ditsinon can be applied locally (e.g., skin graft, tooth extraction) using a sterile gauze pad moistened with the drug. Combined use of the oral form with parenteral administration is possible.

Hepatic and renal impairment. There is insufficient clinical data to provide dosing recommendations; therefore, the drug should be used with caution in such patients.

Children.

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

Overdose.

Data are lacking. In case of overdose, symptomatic treatment should be administered.

Side effects.

Central and peripheral nervous system: headache, dizziness, hot flushes, paresthesia of lower limbs.

Cardiovascular system: thromboembolism, arterial hypotension, reduced tissue perfusion which spontaneously recovers after some time.

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

Immune system: allergic reactions, hypersensitivity, skin rash, urticaria, pruritus, anaphylactic shock, exacerbation of bronchial asthma; one case of angioneurotic edema has been reported.

Blood and lymphatic system: agranulocytosis, neutropenia, thrombocytopenia.

Musculoskeletal system: arthralgia.

Other: asthenia, fever, bronchospasm, acute porphyria.

Local reactions at injection site: pruritus, erythema.

All adverse effects are mild and transient.

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

Incompatibility.

Ethamsylate solution is incompatible with solutions of sodium bicarbonate and sodium lactate.

Pharmaceutically incompatible (in the same syringe) with other medicinal products.

Shelf life. 5 years.

Storage conditions.

Store at a temperature not exceeding 25 °C in a light-protected place.

Keep out of reach of children.

Packaging.

2 ml solution in an ampoule; 50 ampoules per cardboard box.

Prescription status. Prescription only.

Manufacturer.

Lek Pharmaceuticals d. d.

Manufacturer's address and place of business.

Verovškova 57, Ljubljana 1526, Slovenia.