Daltep (Solution) Instructions for Use

Marketing Authorization Holder

Pharmasintez, JSC (Russia)

ATC Code

B01AB04 (Dalteparin)

Active Substance

Dalteparin sodium (Rec.INN registered by WHO)

Dosage Forms

	Daltep	Solution for subcutaneous injection 2500 anti-Xa IU/0.2 ml: syringes 10 pcs.
		Solution for subcutaneous injection 5000 anti-Xa IU/0.2 ml: syringes 10 pcs.

Dosage Form, Packaging, and Composition

Solution for s.c. injection transparent, colorless or with a yellowish tint.

Excipients : sodium chloride – 0.3 mg, hydrochloric acid 0.1M solution or sodium hydroxide 0.1M solution to pH 5.0-7.5, water for injections – up to 0.2 ml.

0.2 ml – syringes (5) – contour blisters (2) – cardboard packs.

Solution for s.c. injection transparent, colorless or with a yellowish tint.

Excipients : hydrochloric acid 0.1M solution or sodium hydroxide 0.1M solution to pH 5.0-7.5, water for injections – up to 0.2 ml.

0.2 ml – syringes (5) – contour blisters (2) – 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 (average molecular weight 4000-6000 daltons) isolated from the porcine intestinal 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 s.c. injection, the bioavailability is about 90%.

T_1/2 after i.v. injection is 2 hours, after s.c. – 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 the recurrence of venous thromboembolic complications in patients with malignant neoplasms.

ICD codes

Dosage Regimen

Determine the dosage individually based on indication, clinical status, body weight, and renal function.

Administer by subcutaneous injection only. Do not administer intramuscularly.

For treatment of acute deep vein thrombosis or pulmonary embolism, administer 200 IU/kg body weight once daily. The maximum single dose is 18,000 IU. Alternatively, administer 100 IU/kg twice daily. Continue treatment for at least 5 days and until adequate oral anticoagulation is achieved.

For unstable angina or non-ST-elevation myocardial infarction, administer 120 IU/kg body weight every 12 hours. The maximum single dose is 10,000 IU. Concurrent low-dose acetylsalicylic acid therapy is recommended. The usual treatment duration is 5-8 days.

For surgical thromboprophylaxis in general surgery, administer 2500 IU once daily, with the initial dose given 1-2 hours preoperatively. Continue for 5-7 days or until the patient is fully mobile. For high-thrombotic-risk patients, administer 5000 IU once daily.

For medical thromboprophylaxis in acutely ill patients with restricted mobility, administer 5000 IU once daily. The usual treatment duration is 12-14 days.

For long-term secondary prevention of venous thromboembolism in patients with active cancer, administer approximately 150 IU/kg once daily for 30 days. Subsequently, administer approximately 150 IU/kg once daily for 5 months.

In patients with severe renal impairment (creatinine clearance less than 30 ml/min), monitor anti-Xa activity due to an increased risk of bleeding. Consider dose adjustment based on monitoring results.

In elderly patients, particularly those over 80 years, use therapeutic doses with caution due to an increased bleeding risk. Monitor these patients closely.

Rotate subcutaneous injection sites between the left and right anterolateral and posterolateral abdominal wall. Do not expel the air bubble from the syringe before injection to avoid loss of the solution.

Adverse Reactions

From the hematopoietic system and blood coagulation system often – mild thrombocytopenia (type I), usually reversible during treatment, bleeding; frequency unknown – heparin-induced immune thrombocytopenia 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 or suspected heparin-induced immune thrombocytopenia (type II); bleeding (clinically significant, e.g., from the gastrointestinal tract due to gastric and/or duodenal ulcer, intracranial hemorrhages); severe blood coagulation disorders; 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 slight 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 failure.

Pediatric Use

It is possible to use in children according to indications in doses recommended for the respective age. 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 hepatic impairment, uncontrolled arterial hypertension, hypertensive or diabetic retinopathy, with 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 increase aPTT may lead to overdose and bleeding. Tests for determining anti-Xa activity should be used for laboratory monitoring of dalteparin sodium treatment.

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 that developed against the background of unstable angina and myocardial infarction without a pathological Q wave in the case of thrombolytic therapy, discontinuation of dalteparin sodium is not mandatory. However, in such a situation, the risk of bleeding increases.

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

In patients with severe hepatic impairment, a reduction in the dose 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, as well as monitoring of anti-Xa activity.

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.

Drug Interactions

With simultaneous use with antihistamines, cardiac glycosides, tetracycline, ascorbic acid, the effectiveness of dalteparin sodium decreases.

With simultaneous 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, the anticoagulant effect of dalteparin sodium may be enhanced (the risk of bleeding increases).

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.