Fragmin

/ Pfizer

General: DO NOT ADMINISTER DALTEPARIN BY THE INTRAMUSCULAR ROUTE
Treatment of Acute Deep Venous Thrombosis and Pulmonary Embolism: Dalteparin sodium 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 Dalteparin sodium 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.

Patients with active major bleeding.
Patients with a history of heparin induced thrombocytopenia or heparin induced thrombocytopenia with thrombosis.
Patients with prior hypersensitivity to dalteparin sodium (e.g., pruritis, rash, anaphylactic reactions).
Patients undergoing Epidural/Neuraxial anesthesia, do not administer FRAGMIN :

• As a treatment for unstable angina and non-Q-wave MI.
• For prolonged VTE prophylaxis.

Patients with prior hypersensitivity to heparin or pork products.

Risk of Hemorrhage including Spinal/Epidural Hematomas
Spinal or epidural hemorrhage and subsequent hematomas can occur with the associated use of low molecular weight heparins or heparinoids and neuraxial (spinal/epidural) anesthesia or spinal puncture. The risk of these events is higher with the use of post-operative indwelling epidural catheters, with the concomitant use of additional drugs affecting hemostasis such as NSAIDs, with traumatic or repeated epidural or spinal puncture, or in patients with a history of spinal surgery or spinal deformity
To reduce the potential risk of bleeding associated with the concurrent use of dalteparin sodium and epidural or spinal anesthesia/analgesia or spinal puncture, consider the pharmacokinetic profile of dalteparin sodium.
Placement or removal of an epidural catheter or lumbar puncture is best performed when the anticoagulant effect of Dalteparin sodium is low; however, the exact timing to reach a sufficiently low anticoagulant effect in each patient is not known. No additional hemostasis-altering medications should be administered due to the additive effects.
Patients on preoperative dalteparin sodium thromboprophylaxis can be assumed to have altered coagulation. The first postoperative dalteparin sodium thromboprophylaxis dose (2,500 IU) should be administered 6 to 8 hours postoperatively. The second postoperative dose (2,500 or 5,000 IU) should occur no sooner than 24 hours after the first dose. Placement or removal of a catheter should be delayed for at least 12 hours after administration of 2,500 IU once daily of dalteparin sodium, at least 15 hours after the administration of 5,000 IU once daily of dalteparin sodium, and at least 24 hours after the administration of higher doses (200 IU/kg once daily, 120 IU/kg twice daily) of dalteparin sodium. Anti-Xa levels are still detectable at these time points, and these delays are not a guarantee that neuraxial hematoma will be avoided.
Although a specific recommendation for timing of a subsequent dalteparin sodium dose after catheter removal cannot be made, consider delaying this next dose for at least 4 hours, based on a benefit-risk assessment considering both the risk for thrombosis and the risk for bleeding in the context of the procedure and patient risk factors. For patients with creatinine clearance <30mL/minute, additional considerations are necessary because elimination of dalteparin sodium may be more prolonged; consider doubling the timing of removal of a catheter, at least 24 hours for the lower prescribed dose of DALTEPARIN SODIUM (2,500 IU or 5,000 IU once daily) and at least 48 hours for the higher dose (200 IU/kg once daily, 120 IU/kg twice daily).
Should the physician decide to administer anticoagulation in the context of epidural or spinal anesthesia/analgesia or lumbar puncture, frequent monitoring must be exercised to detect any signs and symptoms of neurological impairment such as midline back pain, sensory and motor deficits (numbness or weakness in lower limbs), bowel and/or bladder dysfunction. Instruct patients to report immediately if they experience any of the above signs or symptoms. If signs or symptoms of spinal hematoma are suspected, initiate urgent diagnosis and treatment including consideration for spinal cord decompression even though such treatment may not prevent or reverse neurological sequelae.
Use dalteparin sodium with extreme caution in patients who have an increased risk of hemorrhage, such as those with severe uncontrolled hypertension, bacterial endocarditis, congenital or acquired bleeding disorders, active ulceration and angiodysplastic gastrointestinal disease, hemorrhagic stroke, or shortly after brain, spinal or ophthalmological surgery. dalteparin sodium may enhance the risk of bleeding in patients with thrombocytopenia or platelet defects; severe liver or kidney insufficiency, hypertensive or diabetic retinopathy, and recent gastrointestinal bleeding. bleeding can occur at any site during therapy with dalteparin sodium.
Thrombocytopenia
Heparin-induced thrombocytopenia can occur with the administration of dalteparin sodium. The incidence of this complication is unknown at present. In clinical practice, cases of thrombocytopenia with thrombosis, amputation and death have been observed. Closely monitor thrombocytopenia of any degree.
In dalteparin sodium clinical trials supporting non-cancer indications, platelet counts of < 50,000/mm3 occurred in < 1% of patients.
Laboratory Tests
Periodic routine complete blood counts, including platelet count, blood chemistry, and stool occult blood tests are recommended during the course of treatment with dalteparin sodium. When administered at recommended prophylaxis doses, routine coagulation tests such as Prothrombin Time (PT) and Activated Partial Thromboplastin Time (APTT) are relatively insensitive measures of dalteparin sodium activity and, therefore, unsuitable for monitoring the anticoagulant effect of dalteparin sodium. Anti-Xa may be used to monitor the anticoagulant effect of dalteparin sodium, such as in patients with severe renal impairment or if abnormal coagulation parameters or bleeding occurs during dalteparin sodium therapy.
See prescribing information for full details.

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).

Latex Allergy: Persons with latex allergies should not handle the FRAGMIN prefilled syringe because the needle shield may contain natural rubber latex which may cause allergic reactions.
Subcutaneous injection technique: Patients should be sitting or lying down and  administered by deep subcutaneous injection. The drug  may be injected in a U-shape area around the navel, the upper outer side of the thigh or the upper outer quadrangle of the buttock. The injection site should be varied daily. When the area around the navel or the thigh is used, using the thumb and forefinger, you must lift up a fold of skin while giving the injection. The entire length of the needle should be inserted at a 45 to 90-degree angle.
Inspect dalteparin sodium prefilled syringes and vials visually for particulate matter and discoloration prior to administration