FRAGMIN (DALTEPARIN SODIUM) 2500IU SOLUTION FOR INJECTION

Indications

• Prevention of venous thromboembolism in patients undergoing surgery
• Treatment of deep vein thrombosis
• Treatment of pulmonary embolism
• Prevention of thromboembolic complications in high-risk patients

Dosage

Children: Refer to the BNF for Children for dosing recommendations tailored to paediatric patients.

Adults: Refer to the BNF for specific dosing guidelines based on the indication and patient factors.

Mechanism of action

Dalteparin exerts its anticoagulant effects by binding to antithrombin III, which leads to the inactivation of factor Xa and, to a lesser extent, factor IIa (thrombin). This action inhibits the conversion of fibrinogen to fibrin, preventing clot formation. The binding to antithrombin enhances its activity, resulting in an increased rate of inhibition of coagulation factors.

Pharmacodynamics

The anticoagulant effect of dalteparin is dose-dependent, providing a predictable response that allows for a more standardized dosing regimen compared to unfractionated heparin. It has a longer half-life and a more stable anticoagulant response, which can reduce the need for frequent monitoring of coagulation parameters like activated partial thromboplastin time (aPTT).

Pharmacokinetics

Dalteparin is administered via subcutaneous injection, with a bioavailability of approximately 87%. It is primarily eliminated by the kidneys, and its half-life is about 2 to 4 hours in patients with normal renal function. The pharmacokinetics may be altered in patients with renal impairment, necessitating careful monitoring and potential dose adjustment.

Contra-indications

• Active bleeding
• Severe thrombocytopenia
• History of heparin-induced thrombocytopenia
• Hypersensitivity to dalteparin or any component of the formulation
• Severe renal impairment

Adverse effects

• Bleeding complications
• Thrombocytopenia
• Injection site reactions
• Elevated liver enzymes
• Osteoporosis with long-term use
• Allergic reactions

Interactions

• Other anticoagulants (e.g., warfarin, fondaparinux) may increase bleeding risk
• Non-steroidal anti-inflammatory drugs (NSAIDs) can increase the risk of gastrointestinal bleeding
• Antiplatelet agents may increase the risk of bleeding
• Certain herbal supplements (e.g., ginkgo biloba) may enhance anticoagulant effects

Precautions

• Monitor platelet counts regularly during therapy
• Use with caution in patients with renal impairment
• Careful consideration in patients with a history of bleeding disorders
• Use in elderly patients may require careful monitoring due to increased risk of bleeding

Pregnancy

Dalteparin can be used during pregnancy, particularly for the prevention and treatment of venous thromboembolism, as it does not cross the placenta in significant amounts.

Breast-feeding

Dalteparin is generally considered safe during breastfeeding, as it is not expected to be excreted in significant amounts in breast milk.

Storage

Store at 2 to 8 degrees Celsius. Do not freeze. Protect from light.

Formulations

• Injection solution in pre-filled syringes
• Injection solution in vials

Indications

• Treatment of deep vein thrombosis
• Treatment of pulmonary embolism
• Prophylaxis of deep vein thrombosis in surgical patients
• Unstable coronary artery disease
• Prevention of clotting in extracorporeal circuits

Dosage

Adults: For adults, doses vary based on the indication. For treatment of DVT or PE, the recommended dose is 100 units/kg subcutaneously twice daily until adequate oral anticoagulation is established. For prophylaxis in general surgery, the dose is typically 2500

Mechanism of action

Dalteparin sodium exerts its anticoagulant effects primarily through the inhibition of factor Xa and to a lesser extent factor IIa (thrombin). It enhances the activity of antithrombin III, which inactivates these coagulation factors, preventing the formation of fibrin clots. This mechanism is crucial in managing thrombotic conditions by reducing the blood's ability to clot.

Pharmacodynamics

As a low molecular weight heparin, dalteparin has a unique pharmacodynamic profile, including a dose-dependent anticoagulant response. The inhibition of factor Xa is more pronounced compared to unfractionated heparin, which provides a more stable anticoagulation effect. This results in a reduced risk of bleeding complications and allows for once or twice daily dosing in many clinical scenarios.

Pharmacokinetics

Dalteparin sodium is well-absorbed following subcutaneous administration, with peak plasma concentrations occurring approximately 2-4 hours post-injection. It has a bioavailability of approximately 87%. The elimination half-life is around 3-5 hours in healthy individuals, with renal clearance being the primary route of elimination. Patients with renal impairment may require dosage adjustments due to the risk of accumulation.

Contra-indications

• Recent surgery to the ear
• Severe impairment of pancreatic function
• Unstable coronary artery disease (including non-ST-segment-elevation myocardial infarction)
• Hypersensitivity to unfractionated or low molecular-weight heparin

Adverse effects

• Epidural haematoma
• Hyperkalaemia
• Thrombocytopenia
• Bleeding complications

Precautions

• Caution in renal impairment, especially if creatinine clearance is less than 80 mL/minute
• Consider measuring anti-Factor Xa levels if creatinine clearance is less than 30 mL/minute
• Monitor plasma-potassium concentration in patients at risk of hyperkalaemia

Pregnancy

Caution is advised due to limited information available; no toxicity observed in animal studies and it's not known if dalteparin crosses the placenta.

Breast-feeding

Avoid; no information available regarding safety during breastfeeding.

Storage

Store in a refrigerator (2°C to 8°C). Do not freeze. Protect from light.

Formulations

• Dalteparin sodium 2500 units/0.2 ml solution for injection pre-filled syringes
• Dalteparin sodium 10000 units/1 ml solution for injection pre-filled syringes
• Dalteparin sodium 12500 units/1 ml solution for injection pre-filled syringes
• Dalteparin sodium 10000 units/4 ml solution for injection ampoules