Detrombin^® (Solution) Instructions for Use

Marketing Authorization Holder

Pharmfirma Sotex, CJSC (Russia)

ATC Code

B01AB06 (Nadroparin)

Active Substance

Nadroparin calcium (Rec.INN registered by WHO)

Dosage Forms

	Detrombin®	Solution for subcutaneous injection 9500 IU anti-Xa/1 ml: syringes 0.3 ml 2 or 10 pcs.
		Solution for subcutaneous injection 9500 IU anti-Xa/1 ml: syringes 0.4 ml 2 or 10 pcs.
		Solution for subcutaneous injection 9500 IU anti-Xa/1 ml: syringes 0.5 ml 2 or 10 pcs.
		Solution for subcutaneous injection 9500 IU anti-Xa/1 ml: syringes 0.6 ml 2 or 10 pcs.
		Solution for subcutaneous injection 9500 IU anti-Xa/1 ml: syringes 0.7 ml 2 or 10 pcs.
		Solution for subcutaneous injection 9500 IU anti-Xa/1 ml: syringes 0.8 ml 2 or 10 pcs.
		Solution for subcutaneous injection 9500 IU anti-Xa/1 ml: syringes 0.9 ml 2 or 10 pcs.
		Solution for subcutaneous injection 9500 IU anti-Xa/1 ml: syringes 1 ml 2 or 10 pcs.

Dosage Form, Packaging, and Composition

Solution for subcutaneous injection colorless or from light yellow to brownish-yellow, transparent or with slight opalescence.

Excipients : calcium hydroxide solution 0.1% or hydrochloric acid solution 0.1M, water for injections.

0.3 ml (2850 IU anti-Xa) – glass syringes (2) with or without needle protection device – contour cell packaging (1) – cardboard packs.
0.3 ml (2850 IU anti-Xa) – glass syringes (2) with or without needle protection device – contour cell packaging (5) – cardboard packs.

Solution for subcutaneous injection colorless or from light yellow to brownish-yellow, transparent or with slight opalescence.

Excipients : calcium hydroxide solution 0.1% or hydrochloric acid solution 0.1M, water for injections.

0.4 ml (3800 IU anti-Xa) – glass syringes (2) with or without needle protection device – contour cell packaging (1) – cardboard packs.
0.4 ml (3800 IU anti-Xa) – glass syringes (2) with or without needle protection device – contour cell packaging (5) – cardboard packs.

Solution for subcutaneous injection colorless or from light yellow to brownish-yellow, transparent or with slight opalescence.

Excipients : calcium hydroxide solution 0.1% or hydrochloric acid solution 0.1M, water for injections.

0.5 ml (4750 IU anti-Xa) – glass syringes (2) with or without needle protection device – contour cell packaging (1) – cardboard packs.
0.5 ml (4750 IU anti-Xa) – glass syringes (2) with or without needle protection device – contour cell packaging (5) – cardboard packs.

Solution for subcutaneous injection colorless or from light yellow to brownish-yellow, transparent or with slight opalescence.

Excipients : calcium hydroxide solution 0.1% or hydrochloric acid solution 0.1M, water for injections.

0.6 ml (5700 IU anti-Xa) – glass syringes (2) with or without needle protection device – contour cell packaging (1) – cardboard packs.
0.6 ml (5700 IU anti-Xa) – glass syringes (2) with or without needle protection device – contour cell packaging (5) – cardboard packs.

Solution for subcutaneous injection colorless or from light yellow to brownish-yellow, transparent or with slight opalescence.

Excipients : calcium hydroxide solution 0.1% or hydrochloric acid solution 0.1M, water for injections.

0.7 ml (6650 IU anti-Xa) – glass syringes (2) with or without needle protection device – contour cell packaging (1) – cardboard packs.
0.7 ml (6650 IU anti-Xa) – glass syringes (2) with or without needle protection device – contour cell packaging (5) – cardboard packs.

Solution for subcutaneous injection colorless or from light yellow to brownish-yellow, transparent or with slight opalescence.

Excipients : calcium hydroxide solution 0.1% or hydrochloric acid solution 0.1M, water for injections.

0.8 ml (7600 IU anti-Xa) – glass syringes (2) with or without needle protection device – contour cell packaging (1) – cardboard packs.
0.8 ml (7600 IU anti-Xa) – glass syringes (2) with or without needle protection device – contour cell packaging (5) – cardboard packs.

Solution for subcutaneous injection colorless or from light yellow to brownish-yellow, transparent or with slight opalescence.

Excipients : calcium hydroxide solution 0.1% or hydrochloric acid solution 0.1M, water for injections.

0.9 ml (8550 IU anti-Xa) – glass syringes (2) with or without needle protection device – blisters (1) – cardboard packs.
0.9 ml (8550 IU anti-Xa) – glass syringes (2) with or without needle protection device – blisters (5) – cardboard packs.

Solution for subcutaneous injection colorless or from light yellow to brownish-yellow, transparent or with slight opalescence.

Excipients : calcium hydroxide solution 0.1% or hydrochloric acid solution 0.1M, water for injections.

1 ml (9500 IU anti-Xa) – glass syringes (2) with or without needle protection device – cardboard cell packaging (1) – cardboard packs.
1 ml (9500 IU anti-Xa) – glass syringes (2) with or without needle protection device – contour cell packaging (5) – cardboard packs.

Clinical-Pharmacological Group

Direct-acting anticoagulant – low molecular weight heparin

Pharmacotherapeutic Group

Direct-acting anticoagulant agent

Pharmacological Action

Direct-acting anticoagulant; it is a low molecular weight heparin (molecular weight 4500 daltons), obtained from standard heparin by depolymerization.

Compared to heparin, it is characterized by pronounced activity against factor Xa and weak activity against factor IIa. The anti-Xa activity of nadroparin calcium is more pronounced than its effect on APTT. It has a less pronounced effect on platelet aggregation.

Pharmacokinetics

C_max is reached 3 hours after administration. 98% of the active substance is present in the blood in a biologically active form. T_1/2 – 3.5 hours with subcutaneous administration.

Indications

Prevention of thromboembolic complications (during surgical and orthopedic interventions; in patients with a high risk of thrombosis with acute respiratory and/or heart failure in the ICU); treatment of thromboembolism; prevention of blood clotting during hemodialysis; treatment of unstable angina and myocardial infarction without Q wave.

ICD codes

Dosage Regimen

Administer subcutaneously into the abdominal wall. Select the dose, frequency, and duration strictly individually based on the specific indication and the patient’s body weight.

For prophylaxis of thromboembolic complications in general surgery: administer 2850 IU (0.3 ml) once daily, with the first dose given 2-4 hours pre-operatively. Continue for at least 7 days or until the patient is fully ambulatory.

For prophylaxis in high-risk medical patients: administer 38 IU/kg (0.4 ml/10 kg) once daily. The standard duration is 10-14 days.

For prophylaxis in orthopedic surgery: administer 38 IU/kg 12 hours pre-operatively. Continue with the same dose once daily or administer 38 IU/kg 12 hours post-operatively, then once daily.

For treatment of deep vein thrombosis with or without pulmonary embolism: administer 85 IU/kg (0.9 ml/10 kg) every 12 hours. Alternatively, for outpatient treatment, administer 171 IU/kg (1.8 ml/10 kg) once daily. Concurrent oral anticoagulation should be initiated and nadroparin continued for at least 5 days until a stable INR is achieved.

For unstable angina and non-Q-wave myocardial infarction: administer 86 IU/kg every 12 hours in combination with acetylsalicylic acid. The usual treatment duration is 2-8 days.

For prevention of clotting in extracorporeal circulation during hemodialysis: administer into the arterial line of the circuit at a dose of 65 IU/kg. For sessions longer than 4 hours, administer an additional dose of 10-15 IU/kg.

Do not administer intramuscularly. Routinely monitor platelet counts during therapy. In patients with renal impairment (CrCl <30 ml/min), use with extreme caution for therapeutic doses due to the increased risk of bleeding.

Adverse Reactions

From the blood coagulation system bleeding of various locations, more often in patients with other risk factors.

From the hematopoietic system thrombocytopenia, eosinophilia (reversible).

From the immune system very rarely – hypersensitivity reactions (including angioedema and skin reactions).

From the liver and biliary tract increased activity of hepatic transaminases (usually transient).

Allergic reactions angioedema, skin reactions.

Local reactions very often – formation of a small subcutaneous hematoma at the injection site; in some cases, the appearance of dense nodules (not meaning heparin encapsulation) is observed, which disappear after a few days; very rarely – skin necrosis, usually at the injection site. The development of necrosis is usually preceded by purpura or an infiltrated or painful erythematous spot, which may or may not be accompanied by general symptoms (in such cases, the use of nadroparin calcium should be discontinued immediately).

Other: very rarely – priapism, reversible hyperkalemia (associated with the ability of heparins to suppress aldosterone secretion, especially in patients at risk).

Contraindications

Hypersensitivity to nadroparin calcium; diseases and conditions accompanied by impaired blood coagulation processes, acute septic endocarditis, intracranial hemorrhage; severe renal failure (creatinine clearance less than 30 ml/min) in patients receiving Nadroparin calcium for the treatment of thromboembolism, unstable angina and myocardial infarction without Q wave; children and adolescents under 18 years of age.

With caution in hepatic insufficiency, in renal insufficiency, in severe arterial hypertension, in history of peptic ulcers or other diseases with an increased risk of bleeding, in circulatory disorders in the choroid and retina, in the postoperative period after operations on the brain and spinal cord or on the eyes, in patients weighing less than 40 kg; in case of treatment duration exceeding the recommended one; in case of non-compliance with the recommended treatment conditions (especially duration and dose setting based on body weight for course use); when combined with drugs that increase the risk of bleeding.

Use in Pregnancy and Lactation

During pregnancy, it should be used only after consultation with a doctor, in cases where the intended benefit to the mother outweighs the potential risk to the fetus.

Currently, there are limited data regarding the excretion of nadroparin in breast milk. In this regard, use during breastfeeding is not recommended.

Use in Hepatic Impairment

It should be used with caution in patients with hepatic insufficiency.

Use in Renal Impairment

Contraindicated for use in severe renal failure (creatinine clearance less than 30 ml/min) in patients receiving Nadroparin calcium for the treatment of thromboembolism. It should be used with caution in patients with renal insufficiency.

Pediatric Use

Use in children and adolescents under 18 years of age is contraindicated.

Geriatric Use

In elderly patients, dose adjustment is not required, except for patients with impaired renal function. Before starting treatment with Fraxiparine, it is recommended to assess renal function.

Special Precautions

Nadroparin calcium is not intended for intramuscular injection.

During treatment with nadroparin calcium, clinical monitoring of platelet count measurement should be carried out.

Drug Interactions

With simultaneous use, antiplatelet agents, indirect anticoagulants, NSAIDs (including acetylsalicylic acid), fibrinolytics, dextran, clopidogrel, eptifibatide, iloprost, ticlopidine potentiate the antiplatelet effect, increase the risk of bleeding.

Nadroparin calcium should be prescribed with caution to patients receiving oral anticoagulants, systemic corticosteroids and dextrans. When prescribing oral anticoagulants to patients receiving Nadroparin calcium, its use should be continued until the prothrombin time indicator stabilizes to the required value.

With simultaneous use of nadroparin calcium and drugs that can cause hyperkalemia (including potassium salts, potassium-sparing diuretics, ACE inhibitors, angiotensin II receptor blockers, NSAIDs, heparins, cyclosporine, tacrolimus, trimethoprim), the risk of hyperkalemia increases.

When combined with systemic corticosteroids, caution is required.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.