FRAGMIN

What it is

FRAGMIN is dalteparin sodium, a low molecular weight heparin. It is presented as a clear colourless or straw-coloured solution for injection. FRAGMIN is available in seven strengths: 2,500 IU, 5,000 IU, 7,500 IU, 10,000 IU, 12,500 IU, 15,000 IU and 18,000 IU (anti-Xa) per syringe.

Approved indications

— Prophylaxis against thrombotic complications during haemodialysis. — Treatment of acute deep vein thrombosis (DVT). — Extended treatment of symptomatic venous thromboembolism (proximal deep vein thrombosis and/or pulmonary embolism) to reduce the recurrence of VTE in patients with solid tumour cancers. — Treatment of unstable coronary artery disease, including unstable angina and non-ST-elevation myocardial infarction. — Prophylaxis against thromboembolic complications in the peri- or post-operative period of surgery.

Dosing overview

Dosing varies by indication. FRAGMIN should not be administered by the intramuscular route. For thromboprophylaxis in conjunction with general surgery, 2,500 IU is administered subcutaneously 1–2 hours before the operation and thereafter 2,500 IU subcutaneously each morning until the patient is mobilised, generally 5–7 days. For high-risk general surgery, 5,000 IU is given subcutaneously the evening before operation and 5,000 IU subcutaneously the following evenings, or alternatively 2,500 IU subcutaneously 1–2 hours before operation and 2,500 IU subcutaneously twelve hours later, with 5,000 IU subcutaneously each morning on following days, continuing until the patient is mobilised, generally 5–7 days. For prolonged thromboprophylaxis in orthopaedic surgery, 5,000 IU is given subcutaneously the evening before operation and 5,000 IU subcutaneously the following evenings, continuing for five post-operative weeks. For treatment of acute deep vein thrombosis, the initial dosage is subcutaneous injections of 100 IU/kg twice daily or 100 IU/kg administered during 12 hours as continuous intravenous infusion. For extended treatment of symptomatic VTE in patients with cancer, month 1 dosing is 200 IU/kg total body weight subcutaneously once daily (not exceeding 18,000 IU daily). Months 2–6 dosing is approximately 150 IU/kg subcutaneously once daily (not exceeding 18,000 IU daily). For treatment of unstable coronary artery disease, 120 IU/kg body weight is administered subcutaneously twice daily (maximum dose 10,000 IU/12 hours) for 6 days.

Key safety warnings

When neuraxial anaesthesia or spinal puncture is employed, patients anticoagulated with low molecular weight heparins are at risk of developing an epidural or spinal haematoma which can result in long-term or permanent paralysis. The risk is increased by indwelling epidural catheters and concurrent use of drugs affecting haemostasis such as NSAIDs, platelet inhibitors or other anticoagulants, as well as by traumatic or repeated epidural or spinal puncture. As with all antithrombotic agents, there is a risk of systemic bleeding with FRAGMIN administration. FRAGMIN should be used with caution in patients at higher risk of haemorrhage, including those with cancer, thrombocytopenia, platelet disorders, severe liver or kidney insufficiency, uncontrolled hypertension or hypertensive or diabetic retinopathy, and those receiving concurrent anticoagulant or antiplatelet agents. Thrombocytopenia of any degree should be monitored closely. Special precautions should be taken with FRAGMIN use in conjunction with thrombocytopenia or disorders of platelet function. It is recommended that platelets be counted before starting treatment and monitored regularly. Special caution is necessary in rapidly developing thrombocytopenia and severe thrombocytopenia (<100,000/μL) during administration of FRAGMIN. Heparin and low molecular weight heparin can suppress adrenal secretion of aldosterone leading to hyperkalaemia, particularly in patients with diabetes mellitus, chronic renal failure, pre-existing metabolic acidosis, raised plasma potassium or taking potassium sparing drugs. Plasma potassium should be measured in patients at risk. Long term treatment with heparin has been associated with a risk of osteoporosis. The risk of osteoporosis with dalteparin cannot be excluded. Caution should be observed in patients with known osteoporosis and spontaneous fractures.

Contraindications

Hypersensitivity to FRAGMIN, other low molecular weight heparins and/or heparins, or pork products, including a history of confirmed or suspected immunologically mediated heparin-induced thrombocytopenia, is contraindicated. Ulcerative conditions showing a tendency to haemorrhage (such as gastrointestinal ulcer or ulcerative colitis) are contraindicated. Cerebral haemorrhage and severe coagulation disorder are contraindicated. Acute or sub-acute septic endocarditis is contraindicated. FRAGMIN should not be used following injuries to or surgery involving brain, spinal cord, eye or ears.

Regulatory history

FRAGMIN dalteparin sodium 2,500 anti-Xa IU/0.2 mL and 5,000 anti-Xa IU/0.2 mL injection syringes were first listed on the ARTG on 21 October 1991. The 12,500 anti-Xa IU/0.5 mL, 15,000 anti-Xa IU/0.6 mL and 18,000 anti-Xa IU/0.72 mL injection syringe strengths were first listed on 11 November 1997. The 7,500 anti-Xa IU/0.75 mL and 10,000 anti-Xa IU/1 mL graduated syringes were first listed on 23 November 1998.