Fragmin

/ Pfizer

General: DO NOT ADMINISTER DALTEPARIN BY THE INTRAMUSCULAR ROUTE
Compatibility with IV Solutions – Dalteparin is compatible with isotonic sodium chloride (9 mg/mL) or isotonic glucose (50 mg/mL) infusion solution in glass bottles and plastic containers.
Treatment of Acute Deep Venous Thrombosis and Pulmonary Embolism: Fragmin can be administered subcutaneously either as a single daily injection or as two daily injections. Once daily administration:200 IU/kg body weight is administered SC once daily. Monitoring of the anticoagulant effect is not necessary. The single daily dose should not exceed 18000 IU. Twice daily administration: Alternatively, a dose of 100 IU/kg total body weight administered SC twice daily may be given. Monitoring of the anticoagulant effect is generally not necessary but should be considered for specific patient populations. Maximum plasma levels are obtained 3-4 hours after s.c. injection when samples should be taken. Recommended plasma levels are between 0.5-1.0 IU anti-Xa/ml. Simultaneous anticoagulation with oral vitamin K antagonists can be started immediately. Treatment with Fragmin is continued until the prothrombin complex levels (factor II, VII, IX and X) have decreased to a therapeutic level. At least five days of combined treatment is
normally required. Outpatient treatment is feasible using the same doses recommended for treatment in a medical institution.
For full details see prescribing information.

Treatment of acute deep venous thrombosis and/or pulmonary embolism.
Prevention of clotting during haemodialysis and haemofiltration in connection with acute renal failure or chronic renal insufficiency.
Thromboprophylaxis in conjunction with surgery.
Unstable coronary artery disease.
Prophylaxis in patients with substantially increased risk for venous thromboembolism and that are temporarily immobilized due to acute illness such as cardiac insufficiency, respiratory insufficiency and severe infections.
Cancer patients: Treatment and secondary prevention of deep-vein thrombosis and/or pulmonary embolism.

Hypersensitivity to dalteparin, or other low molecular weight heparins or heparins, or pork products.
Confirmed or suspected history of immunologically mediated heparin induced thrombocytopenia.
Active, clinically-significant bleeding (such as gastrointestinal ulceration or bleeding, or cerebral haemorrhage).
Severe coagulation disorders.
Septic endocarditis.
Recent Injury to, or surgical procedures of, the central nervous system, eyes and/or ears.
Because of an increased risk of bleeding, high doses of dalteparin (such as those needed to treat acute deep-vein thrombosis, pulmonary embolism, and unstable coronary artery disease) should not be used in patients who will receive spinal or epidural anesthesia or other procedures requiring spinal puncture.

Epidural or Spinal Anesthesia: When neuraxial anesthesia (epidural/spinal anesthesia) or spinal puncture is employed, patients anticoagulated or scheduled to be anticoagulated with low molecular weight heparins or heparinoids for prevention of thromboembolic complications are at risk of developing an epidural or spinal hematoma, which can result in long-term or permanent paralysis. The risk of these events is increased by use of indwelling epidural catheters for administration of analgesia or by the concomitant use of drugs affecting homeostasis such as non-steroidal anti-inflammatory drugs (NSAID’s), platelet inhibitors, or other anticoagulants. The risk also appears to be increased by traumatic or repeated epidural or spinal puncture. Patients should be frequently monitored for signs and symptoms of neurological impairment. If neurologic compromise is noted, urgent treatment (spinal cord decompression) is necessary.
Risk of Hemorrhage: Dalteparin should be used with caution in patients who have a potentially higher risk of hemorrhage, such as patients with thrombocytopenia, platelet disorders, severe liver or kidney insufficiency, uncontrolled hypertension, or hypertensive or diabetic retinopathy. High doses of dalteparin, such as those needed to treat deep-vein thrombosis, pulmonary embolism, or unstable coronary artery disease, should be used with caution in patients who had a recent surgical procedure.
Thrombocytopenia: It is recommended that the platelets be counted before the initiation of dalteparin treatment and be followed regularly during treatment. Special caution is necessary if thrombocytopenia develops rapidly or to a significant degree (less than 100,000/µL or mm3 ) during treatment with dalteparin. In either case, an in vitro test for antiplatelet antibodies in the presence of heparins or low molecular weight heparins is recommended. If the result of the in vitro test is positive or inconclusive, or no test is performed, treatment with dalteparin should be stopped.
Monitoring Anti-Xa Levels: Monitoring of the anticoagulant effect of dalteparin is generally not necessary but should be considered for specific patient populations such as pediatrics; those with renal failure; or those who are very thin or morbidly obese, pregnant, or at increased risk for bleeding or rethrombosis. Laboratory assays using a chromogenic substrate are considered the method of choice for measuring anti-Xa levels. Activated Partial Thromboplastin Time (APTT) or thrombin time should not be used because these tests are relatively insensitive to the activity of dalteparin. Increasing the dose of dalteparin in an attempt to prolong APTT may result in bleeding.
Hyperkalemia: Heparin and low molecular weight Heparin can suppress adrenal secretion of aldosterone leading to hyperkalaemia, particularly in patients such as those 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.
Interchangeability With Other Anticoagulants: Dalteparin cannot be used interchangeably (unit for unit) with unfractionated heparin, other low molecular weight heparins, or synthetic polysaccharides. Each of these medicines differ in their starting raw materials, manufacturing process, physico-chemical, biological, and clinical properties, leading to differences in biochemical identity, dosing, and possibly clinical efficacy and safety. Each of these medicines is unique and has its own instructions for use.
Osteoporosis: Long term treatment with heparin has been associated with a risk of osteoporosis. Although this has not been observed with dalteparin the risk of osteoporosis cannot be excluded.
Pediatric Patients: There is limited safety and efficacy information on the use of dalteparin in pediatric patients. If dalteparin is used in these patients, anti-Xa levels should be monitored.The administration of medications containing benzyl alcohol as a preservative to premature neonates has been associated with a fatal “Gasping Syndrome”. Because benzyl alcohol may cross the placenta, [dalteparin] multiple-dose vials, preserved with benzyl alcohol, should be used with caution in pregnant women and only if clearly needed.
Geriatric Patients: Elderly patients (especially patients aged eighty years and above) may be at an increased risk for bleeding complications within the therapeutic dosage ranges. Careful clinical monitoring is advised.
For full details see prescribing information.

Bleeding at high doses, transient raised liver enzymes, type I and II thrombocytopenia, allergic reactions. Hypoaldosteronism leading to hyperkalemia, monitor serum potassium particularly in patients treated for more than 7 days or those with diabetes, chronic renal failure, pre-existing acidosis, or if taking K⁺-sparing drugs.
For full details see prescribing information.

Concomitant use of drugs affecting hemostasis, such as thrombolytic agents, other anticoagulants, nonsteroidal anti-inflammatory drugs, or platelet inhibitors, or dextran may enhance the anticoagulant effect of dalteparin Unstable Coronary Artery Disease (Unstable Angina and Non-ST-elevation Myocardial Infarction)). Because NSAIDs and ASA analgesic/anti-inflammatory doses reduce production of vasodilatatory prostaglandins, and thereby renal blood flow and the renal excretion, particular care should be taken when administering dalteparin concomitantly with NSAIDs or high dose ASA in patients with renal failure.
For full details see prescribing information.

Pregnancy: If dalteparin is used during pregnancy; the possibility of fetal harm appears remote. However, because the possibility of harm cannot be completely ruled out, dalteparin should be used during pregnancy only if clearly needed.
Lactation: Limited data are available for excretion of dalteparin in human milk. One study in 15 lactating women receiving prophylactic doses of dalteparin detected small amounts of antiXa activity in breast milk, equivalent to a milk/plasma ratio of <0.025-0.224. As oral absorption of low molecular weight heparin is extremely low the clinical implications, if any, of this small amount of anticoagulant activity on the nursing infant are unknown.

The anticoagulant effect induced by dalteparin sodium is inhibited by protamine. However, protamine has an inhibiting effect on primary hemostasis and should be used only in an emergency. A dose of 1 mg of protamine partially neutralizes the effect of 100 IU (anti-Xa) of dalteparin (although the induced prolongation of the clotting time is fully neutralized, 25 to 50% of the anti-Xa activity of dalteparin remains).