Dalfra-Pro (Solution) Instructions for Use

Marketing Authorization Holder

Promomed Rus LLC (Russia)

Manufactured By

Biokhimik, JSC (Russia)

ATC Code

B01AB04 (Dalteparin)

Active Substance

Dalteparin sodium (Rec.INN registered by WHO)

Dosage Forms

	Dalfra-Pro	Solution for intravenous and subcutaneous administration 2500 anti-Xa IU/0.2 ml: syringes 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15 or 20 pcs.
		Solution for intravenous and subcutaneous administration 5000 anti-Xa IU/0.2 ml: syringes 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15 or 20 pcs.
		Solution for intravenous and subcutaneous administration 7500 anti-Xa IU/0.3 ml: syringes 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15 or 20 pcs.
		Solution for intravenous and subcutaneous administration 10000 anti-Xa IU/0.4 ml: syringes 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15 or 20 pcs.
		Solution for intravenous and subcutaneous administration 10000 anti-Xa IU/1.0 ml: amp. 1, 2, 3, 4 or 5 pcs., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15 or 20 pcs.
		Solution for intravenous and subcutaneous administration 12500 IU (anti-Xa)/0.5 ml: syringes 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15 or 20 pcs.
		Solution for intravenous and subcutaneous administration 15000 IU (anti-Xa)/0.6 ml: syringes 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15 or 20 pcs.
		Solution for intravenous and subcutaneous administration 18000 IU (anti-Xa)/0.72 ml: syringes 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15 or 20 pcs.

Dosage Form, Packaging, and Composition

Solution for IV and SC administration transparent colorless or yellowish in color.

Excipients: sodium chloride, sodium hydroxide and/or hydrochloric acid (for pH adjustment), water for injection.

0.2 ml – syringes of colorless glass (1) – cardboard packs with an insert.
0.2 ml – syringes of colorless glass (2) – cardboard packs with an insert.
0.2 ml – syringes of colorless glass (3) – cardboard packs with an insert.
0.2 ml – syringes of colorless glass (4) – cardboard packs with an insert.
0.2 ml – syringes of colorless glass (5) – cardboard packs with an insert.
0.2 ml – syringes of colorless glass (6) – cardboard packs with an insert.
0.2 ml – syringes of colorless glass (7) – cardboard packs with an insert.
0.2 ml – syringes of colorless glass (8) – cardboard packs with an insert.
0.2 ml – syringes of colorless glass (9) – cardboard packs with an insert.
0.2 ml – syringes of colorless glass (10) – cardboard packs with an insert.
0.2 ml – syringes of colorless glass (15) – cardboard packs with an insert.
0.2 ml – syringes of colorless glass (20) – cardboard packs with an insert.

Solution for IV and SC administration transparent colorless or yellowish in color.

Excipients: sodium chloride, sodium hydroxide and/or hydrochloric acid (for pH adjustment), water for injection.

0.2 ml – syringes of colorless glass (1) – cardboard packs with an insert.
0.2 ml – syringes of colorless glass (2) – cardboard packs with an insert.
0.2 ml – syringes of colorless glass (3) – cardboard packs with an insert.
0.2 ml – syringes of colorless glass (4) – cardboard packs with an insert.
0.2 ml – syringes of colorless glass (5) – cardboard packs with an insert.
0.2 ml – syringes of colorless glass (6) – cardboard packs with an insert.
0.2 ml – syringes of colorless glass (7) – cardboard packs with an insert.
0.2 ml – syringes of colorless glass (8) – cardboard packs with an insert.
0.2 ml – syringes of colorless glass (9) – cardboard packs with an insert.
0.2 ml – syringes of colorless glass (10) – cardboard packs with an insert.
0.2 ml – syringes of colorless glass (15) – cardboard packs with an insert.
0.2 ml – syringes of colorless glass (20) – cardboard packs with an insert.

Solution for IV and SC administration transparent colorless or yellowish in color.

Excipients: sodium chloride, sodium hydroxide and/or hydrochloric acid (for pH adjustment), water for injection.

0.3 ml – syringes of colorless glass (1) – cardboard packs with an insert.
0.3 ml – syringes of colorless glass (2) – cardboard packs with an insert.
0.3 ml – syringes of colorless glass (3) – cardboard packs with an insert.
0.3 ml – syringes of colorless glass (4) – cardboard packs with an insert.
0.3 ml – syringes of colorless glass (5) – cardboard packs with an insert.
0.3 ml – syringes of colorless glass (6) – cardboard packs with an insert.
0.3 ml – syringes of colorless glass (7) – cardboard packs with an insert.
0.3 ml – syringes of colorless glass (8) – cardboard packs with an insert.
0.3 ml – syringes of colorless glass (9) – cardboard packs with an insert.
0.3 ml – syringes of colorless glass (10) – cardboard packs with an insert.
0.3 ml – syringes of colorless glass (15) – cardboard packs with an insert.
0.3 ml – syringes of colorless glass (20) – cardboard packs with an insert.

Solution for IV and SC administration transparent colorless or yellowish in color.

Excipients: sodium chloride, sodium hydroxide and/or hydrochloric acid (for pH adjustment), water for injection.

0.4 ml – syringes of colorless glass (1) – cardboard packs with an insert.
0.4 ml – syringes of colorless glass (2) – cardboard packs with an insert.
0.4 ml – syringes of colorless glass (3) – cardboard packs with an insert.
0.4 ml – syringes of colorless glass (4) – cardboard packs with an insert.
0.4 ml – syringes of colorless glass (5) – cardboard packs with an insert.
0.4 ml – syringes of colorless glass (6) – cardboard packs with an insert.
0.4 ml – syringes of colorless glass (7) – cardboard packs with an insert.
0.4 ml – syringes of colorless glass (8) – cardboard packs with an insert.
0.4 ml – syringes of colorless glass (9) – cardboard packs with an insert.
0.4 ml – syringes of colorless glass (10) – cardboard packs with an insert.
0.4 ml – syringes of colorless glass (15) – cardboard packs with an insert.
0.4 ml – syringes of colorless glass (20) – cardboard packs with an insert.

Solution for IV and SC administration transparent colorless or yellowish in color.

Excipients: sodium chloride, sodium hydroxide and/or hydrochloric acid (for pH adjustment), water for injection.

1.0 ml – ampoules of neutral glass (1) – cardboard packs with an insert.
1.0 ml – ampoules of neutral glass (2) – cardboard packs with an insert.
1.0 ml – ampoules of neutral glass (3) – cardboard packs with an insert.
1.0 ml – ampoules of neutral glass (4) – cardboard packs with an insert.
1.0 ml – ampoules of neutral glass (5) – cardboard packs with an insert.
1.0 ml – syringes of colorless glass (1) – cardboard packs with an insert.
1.0 ml – syringes of colorless glass (2) – cardboard packs with an insert.
1.0 ml – syringes of colorless glass (3) – cardboard packs with an insert.
1.0 ml – syringes of colorless glass (4) – cardboard packs with an insert.
1.0 ml – syringes of colorless glass (5) – cardboard packs with an insert.
1.0 ml – syringes of colorless glass (6) – cardboard packs with an insert.
1.0 ml – syringes of colorless glass (7) – cardboard packs with an insert.
1.0 ml – syringes of colorless glass (8) – cardboard packs with an insert.
1.0 ml – syringes of colorless glass (9) – cardboard packs with an insert.
1.0 ml – syringes of colorless glass (10) – cardboard packs with an insert.
1.0 ml – syringes of colorless glass (15) – cardboard packs with an insert.
1.0 ml – syringes of colorless glass (20) – cardboard packs with an insert.

Solution for IV and SC administration transparent colorless or yellowish in color.

Excipients: sodium chloride, sodium hydroxide and/or hydrochloric acid (for pH adjustment), water for injection.

0.5 ml – syringes of colorless glass (1) – cardboard packs with an insert.
0.5 ml – syringes of colorless glass (2) – cardboard packs with an insert.
0.5 ml – syringes of colorless glass (3) – cardboard packs with an insert.
0.5 ml – syringes of colorless glass (4) – cardboard packs with an insert.
0.5 ml – syringes of colorless glass (5) – cardboard packs with an insert.
0.5 ml – syringes of colorless glass (6) – cardboard packs with an insert.
0.5 ml – syringes of colorless glass (7) – cardboard packs with an insert.
0.5 ml – syringes of colorless glass (8) – cardboard packs with an insert.
0.5 ml – syringes of colorless glass (9) – cardboard packs with an insert.
0.5 ml – syringes of colorless glass (10) – cardboard packs with an insert.
0.5 ml – syringes of colorless glass (15) – cardboard packs with an insert.
0.5 ml – syringes of colorless glass (20) – cardboard packs with an insert.

Solution for IV and SC administration transparent colorless or yellowish in color.

Excipients: sodium chloride, sodium hydroxide and/or hydrochloric acid (for pH adjustment), water for injection.

0.6 ml – syringes of colorless glass (1) – cardboard packs with an insert.
0.6 ml – syringes of colorless glass (2) – cardboard packs with an insert.
0.6 ml – syringes of colorless glass (3) – cardboard packs with an insert.
0.6 ml – syringes of colorless glass (4) – cardboard packs with an insert.
0.6 ml – syringes of colorless glass (5) – cardboard packs with an insert.
0.6 ml – syringes of colorless glass (6) – cardboard packs with an insert.
0.6 ml – syringes of colorless glass (7) – cardboard packs with an insert.
0.6 ml – syringes of colorless glass (8) – cardboard packs with an insert.
0.6 ml – syringes of colorless glass (9) – cardboard packs with an insert.
0.6 ml – syringes of colorless glass (10) – cardboard packs with an insert.
0.6 ml – syringes of colorless glass (15) – cardboard packs with an insert.
0.6 ml – syringes of colorless glass (20) – cardboard packs with an insert.

Solution for IV and SC administration transparent colorless or yellowish in color.

Excipients: sodium chloride, sodium hydroxide and/or hydrochloric acid (for pH adjustment), water for injection.

0.72 ml – syringes of colorless glass (1) – cardboard packs with an insert.
0.72 ml – syringes of colorless glass (2) – cardboard packs with an insert.
0.72 ml – syringes of colorless glass (3) – cardboard packs with an insert.
0.72 ml – syringes of colorless glass (4) – cardboard packs with an insert.
0.72 ml – syringes of colorless glass (5) – cardboard packs with an insert.
0.72 ml – syringes of colorless glass (6) – cardboard packs with an insert.
0.72 ml – syringes of colorless glass (7) – cardboard packs with an insert.
0.72 ml – syringes of colorless glass (8) – cardboard packs with an insert.
0.72 ml – syringes of colorless glass (9) – cardboard packs with an insert.
0.72 ml – syringes of colorless glass (10) – cardboard packs with an insert.
0.72 ml – syringes of colorless glass (15) – cardboard packs with an insert.
0.72 ml – syringes of colorless glass (20) – cardboard packs with an insert.

Clinical-Pharmacological Group

Direct-acting anticoagulant – low molecular weight heparin

Pharmacotherapeutic Group

Antithrombotic agents; heparin group

Pharmacological Action

Direct-acting anticoagulant. It is a low molecular weight heparin (average molecular weight 4000-6000 daltons) isolated from the porcine small intestine mucosa. It binds to plasma antithrombin, resulting in the suppression of some coagulation factors, primarily factor Xa; it slightly inhibits thrombin formation. It has a weak effect on platelet adhesion. It slightly increases aPTT and thrombin time.

Pharmacokinetics

The pharmacokinetic parameters of dalteparin sodium do not change depending on the administered dose. After SC injection, the bioavailability is about 90%.

T_1/2 after IV injection is 2 hours, after SC injection – 3-4 hours. It is excreted mainly by the kidneys.

In patients with severe renal impairment, T_1/2 increases.

Indications

Treatment of acute deep vein thrombosis and pulmonary embolism; prevention of thrombosis during surgical interventions; prevention of thromboembolic complications in patients with an acute-phase therapeutic disease and limited mobility (including conditions requiring bed rest); unstable angina or myocardial infarction without ST-segment elevation on ECG; long-term treatment (up to 6 months) to prevent recurrence of venous thromboembolic complications in patients with malignant neoplasms.

ICD codes

Dosage Regimen

Determine the dosage individually based on indication, clinical situation, body weight, and patient age.

Administer the drug subcutaneously or intravenously; do not administer intramuscularly.

For treatment of acute deep vein thrombosis, administer 200 IU/kg body weight subcutaneously once daily; the maximum single dose is 18,000 IU.

Alternatively, for DVT treatment, use 100 IU/kg body weight subcutaneously twice daily; this regimen is recommended for patients with a high risk of bleeding or complications.

For treatment of pulmonary embolism, use the same regimen as for deep vein thrombosis.

Continue treatment for at least 5 days and until adequate oral anticoagulation is achieved with a vitamin K antagonist.

For unstable angina and non-ST-segment elevation myocardial infarction, administer 120 IU/kg body weight subcutaneously every 12 hours; the maximum single dose is 10,000 IU.

Concomitant use of acetylsalicylic acid is recommended unless contraindicated; treatment typically continues for 5-8 days.

For general surgical prophylaxis, administer 2500 IU subcutaneously 1-2 hours before surgery, then once daily for 5-10 days postoperatively.

For patients at high thrombotic risk, use 5000 IU subcutaneously the evening before surgery, then once daily for 5-10 days postoperatively.

For orthopedic surgery, administer 5000 IU subcutaneously the evening before surgery, then once daily; alternatively, use 2500 IU 4-8 hours postoperatively, then 5000 IU once daily.

For medical patients with acute illness and restricted mobility, administer 5000 IU subcutaneously once daily for 12-14 days.

For long-term secondary prevention in cancer patients with venous thromboembolism, administer approximately 150 IU/kg body weight subcutaneously once daily for the first month, followed by 150 IU/kg once daily for months 2-6.

In patients with severe renal impairment (CrCl < 30 mL/min), monitor anti-Xa activity due to an increased risk of bleeding.

For pediatric patients, base the dose on body weight and monitor anti-Xa activity; the safety of long-term use is not established.

In elderly patients over 80 years, use therapeutic doses with caution due to an increased bleeding risk; implement careful monitoring.

Adverse Reactions

From the hematopoietic system and blood coagulation system often – mild thrombocytopenia (type I), usually reversible during treatment, bleeding; frequency unknown – immune thrombocytopenia, heparin-induced type II, with or without thrombotic complications, spinal or epidural hematoma after corresponding manipulations.

From the immune system: infrequently – hypersensitivity reactions; frequency unknown – anaphylactic reactions.

From the nervous system: frequency unknown – intracranial hemorrhages (including fatal ones).

From the digestive system: frequency unknown – retroperitoneal hemorrhages (including fatal ones).

From the liver and biliary tract: often – transient increase in liver transaminase activity.

From the skin and subcutaneous tissues: rarely – skin necrosis, temporary alopecia; frequency unknown – rash.

Local reactions often – subcutaneous hematoma at the injection site, pain at the injection site.

Contraindications

Hypersensitivity to dalteparin sodium or to other low molecular weight heparins and/or heparin; established history of heparin-induced immune thrombocytopenia (type II) or suspicion thereof; bleeding (clinically significant, e.g., from the gastrointestinal tract due to gastric and/or duodenal ulcer, intracranial hemorrhages); severe disorders of the blood coagulation system; acute or subacute infective endocarditis; recent trauma or surgical interventions on the central nervous system organs, organs of vision and/or hearing; in patients receiving therapy with Dalteparin sodium in therapeutic doses (e.g., for the treatment of acute deep vein thrombosis, pulmonary embolism, unstable angina or myocardial infarction without ST-segment elevation on ECG), local and/or regional anesthesia should not be used during planned surgical interventions.

With caution high doses of dalteparin sodium (e.g., for the treatment of acute deep vein thrombosis, pulmonary embolism, unstable angina or myocardial infarction without ST-segment elevation on ECG) should be used with particular caution in patients in the early postoperative period. Caution should be exercised when using dalteparin sodium in patients with an increased risk of bleeding; this group includes patients with thrombocytopenia, platelet function disorders, severe hepatic or renal failure, uncontrolled arterial hypertension, hypertensive or diabetic retinopathy.

Use in Pregnancy and Lactation

During pregnancy, use is possible only in cases where the intended benefit to the mother outweighs the potential risk to the fetus.

The likelihood of absorption of low molecular weight heparin when taken orally with mother’s milk is very low, the clinical impact of small anticoagulant activity on the newborn is unknown. Caution should be exercised when using dalteparin sodium during breastfeeding.

Use in Hepatic Impairment

Dalteparin sodium should be used with caution in patients with severe hepatic impairment.

Use in Renal Impairment

Caution should be exercised when using dalteparin sodium in patients with severe renal impairment.

Pediatric Use

Use in children is possible according to indications in recommended age-appropriate doses. When using dalteparin in patients of this category, monitoring of anti-Xa activity is necessary. The safety of long-term use of dalteparin sodium in children has not been established.

Geriatric Use

In elderly patients (especially patients over 80 years of age), there is an increased risk of bleeding when using dalteparin sodium in therapeutic doses. In this regard, careful monitoring is recommended.

Special Precautions

Dalteparin sodium should be used with caution in patients with thrombocytopenia or platelet defects, severe liver function impairment, uncontrolled arterial hypertension, hypertensive or diabetic retinopathy, a history of hypersensitivity to heparins or low molecular weight heparins; in patients in the early postoperative period.

Increasing the dose of dalteparin sodium to elevate aPTT may lead to overdose and bleeding. Laboratory monitoring of dalteparin sodium therapy should utilize tests for determining anti-Xa activity.

During emergency hemodialysis, more careful monitoring of anti-Xa activity levels is required due to the narrow range of therapeutic doses for such patients.

In patients with transmural myocardial infarction developing against a background of unstable angina and non-Q-wave myocardial infarction undergoing thrombolytic therapy, discontinuation of dalteparin sodium is not mandatory. However, in this situation, the risk of bleeding increases.

Since NSAIDs in therapeutic doses reduce the production of vasodilating prostaglandins and thus decrease renal blood flow and renal excretion, Dalteparin sodium must be used with particular caution concurrently with this group of drugs in patients with renal insufficiency.

In patients with severe liver impairment, a dose reduction of Dalteparin sodium is necessary, as well as regular monitoring of anti-Xa activity.

In patients on hemodialysis, minor adjustment of dalteparin sodium is usually required, along with monitoring of anti-Xa activity.

In elderly patients (especially those over 80 years of age), there is an increased risk of bleeding when using Dalteparin sodium at therapeutic doses. Therefore, careful monitoring is recommended.

Drug Interactions

Concomitant use with antihistamines, cardiac glycosides, tetracycline, ascorbic acid reduces the effectiveness of dalteparin sodium.

Concomitant use with drugs affecting hemostasis, such as thrombolytic agents (alteplase, streptokinase, urokinase), indirect anticoagulants, vitamin K antagonists, NSAIDs (acetylsalicylic acid, indomethacin, etc.), platelet function inhibitors, or dextran, may enhance the anticoagulant effect of dalteparin sodium (increasing the risk of bleeding).

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.