FRAGMIN 5.000 IU Solution for injection Ref.[10843] Active ingredients: Dalteparin

Peri- and post-operative surgical thromboprophylaxis

Adults

Surgical thromboprophylaxis in patients at high risk of thrombosis: 2,500 IU is administered subcutaneously 1-2 hours before the surgical procedure and 2,500 IU subcutaneously 8-12 hours later. On the following days, 5,000 IU subcutaneously each morning.

As an alternative, 5,000 IU is administered subcutaneously the evening before the surgical procedure and 5,000 IU subcutaneously the following evenings.

Treatment is continued until the patient is mobilised, in general 5-7 days or longer.

Prolonged thromboprophylaxis in hip replacement surgery: 5,000IU is given subcutaneously the evening before the operation and 5,000IU subcutaneously the following evenings. Treatment is continued for five post-operative weeks.

If pre-operative administration of Fragmin is not considered appropriate because the patient is at high risk of haemorrhage during the procedure, post-operative Fragmin may be administered (see Section 5.1).

Prophylaxis of venous thromboembolism in medical patients: The recommended dose of dalteparin sodium is 5,000 IU once daily. Treatment with dalteparin sodium is prescribed for up to 14 days.

Patients with solid tumours: Extended treatment of symptomatic venous thromboembolism (VTE) and prevention of its recurrence.

Month 1:

Administer Fragmin 200 IU/kg total body weight subcutaneously (SC) once daily for the first 30 days of treatment. The total daily dose should not exceed 18,000 IU daily.

^* Maximum dose of 18,000 IU was used in patient weighing up to 132 kg in the CLOT study.
Abbreviations: IU = International Unit

In the case of chemotherapy-induced thrombocytopenia, Fragmin dose should be adopted as follows:

• In patients receiving Fragmin who experience platelet counts between 50,000 and 100,000/mm³, the daily dose of Fragmin should be reduced by 2,500 IU until the platelet count recovers to ≥100,000/mm³.
• In patients receiving Fragmin who experience platelet counts <50,000/mm³, Fragmin should be discontinued until the platelet count recovers above 50,000/mm³.

Months 2-6:

Fragmin should be administered at a dose of approximately 150 IU/kg, subcutaneously, once daily using fixed dose syringes and the table shown below.

Recommended duration of treatment is 6 months (first month of Fragmin treatment is included). Relevance of continuing treatment beyond this period will be evaluated according to individual risk/benefit ratio, taking into account particularly the progression of cancer. No data is available with dalteparin beyond 6 months of treatment in the CLOT study.

In the case of chemotherapy-induced thrombocytopenia, Fragmin dose should be adopted as follows:

• With platelet counts <50,000/mm³, Fragmin dosing should be interrupted until the platelet count recovers above 50,000/mm³.
• For platelet counts between 50,000 and 100,000/mm³, Fragmin should be reduced as illustrated in the table below depending on the patient’s weight. Once the platelet count has recovered to ≥100,000/mm³, Fragmin should be re-instituted at full dose.

Renal failure

In the case of significant renal failure, defined as a creatinine clearance <30 ml/min, the dose of Fragmin should be adjusted based on anti-Factor Xa activity. If the anti-Factor Xa level is below or above the desired range, the dose of Fragmin should be increased or reduced respectively, and the anti-Factor Xa measurement should be repeated after 3-4 new doses. This dose adjustment should be repeated until the desired anti-Factor Xa level is achieved.

As an indication, on the basis of the data available in CLOT, the observed mean levels (min, max) between 4 and 6 hours after administration in patients without severe renal insufficiency were 1.11 IU anti-Factor Xa/ml (0.6; 1.88) and 1.03 IU anti-Factor Xa/ml (0.54; 1.70), respectively, on week 1 and 4 of dalteparin 200 IU/kg OD. Anti-Factor Xa activity determinations were conducted by the chromogenic method.

For patients with an increased risk of bleeding, it is recommended that Fragmin be administered according to the twice daily regimen detailed for Fragmin 10,000 IU/ml ampoules or Fragmin Multidose Vial.

Paediatric population

The safety and efficacy of dalteparin sodium in children has not been established. Currently available data are described in sections 5.1 and 5.2 but no recommendation on a posology can be made.

Monitoring Anti-Xa levels in children

Measurement of peak anti-Xa levels at about 4 hours post-dose should be considered for certain special populations receiving Fragmin, such as children. For therapeutic treatment with doses administered once daily, peak anti-Xa levels should generally be maintained between 0.5 and 1.0 IU/mL measured at 4 hours post-dose. In the case of low and changing physiologic renal function such as in neonates, close monitoring of anti-Xa levels is warranted. For prophylaxis treatment the anti-Xa levels should generally be maintained between 0.2-0.4 IU/mL.

As with all antithrombotic agents, there is a risk of systemic bleeding with Fragmin administration. Care should be taken with Fragmin use in high dose treatment of newly operated patients. After treatment is initiated patients should be carefully monitored for bleeding complications. This may be done by regular physical examination of the patients, close observation of the surgical drain and periodic measurements of hemoglobin, and anti-Xa determinations.

Elderly

Fragmin has been used safely in elderly patients without the need for dosage adjustment.

Method of administration

By subcutaneous injection, preferably into the abdominal subcutaneous tissue anterolaterally or posterolaterally, or into the lateral part of the thigh. Patients should be supine and the total length of the needle should be introduced vertically, not at an angle, into the thick part of a skin fold, produced by squeezing the skin between the thumb and forefinger; the skin fold should be held throughout the injection.

The anticoagulant effect (i.e. prolongation of the APTT) induced by Fragmin is inhibited by protamine. Since protamine itself has an inhibiting effect on primary haemostasis it should be used only in an emergency. The prolongation of the clotting time induced by Fragmin may be fully neutralised by protamine, but the anti-Factor Xa activity is only neutralised to about 25-50%. 1 mg of protamine inhibits the effect of 100 IU (anti-Factor Xa) of Fragmin.

3 years.

Store below 25°C.

Fragmin 5,000 IU/0.2ml solution for injection is supplied in a single dose pre-filled syringe (Type I glass) with a needle shield (rubber), a plunger stopper (chlorobutyl rubber), a plunger rod (polypropylene) and a needle-trap as a safety feature. The needle shield may contain latex (see section 4.4).

Each pack contains 10 syringes.

The Needle-Trap consists of a plastic needle “catcher” which is firmly attached to the syringe label. Together, these two components comprise the Needle-Trap (safety) feature. The Needle-Trap is designed to specifically help prevent accidental needle sticks following the proper administration of injectable medications.

The Needle-Trap requires specific actions by the user to “activate” the Needle-Trap, which will render the needle harmless after the injection is administered:

• The user grasps the tip of the plastic needle catcher and bends it away from needle shield.
• The needle shield is removed from the syringe.
• The injection is administered normally.
• The needle is removed from the patient. The Needle-Trap is activated by placing the plastic catcher against a hard, stable surface and with one hand, pivoting the syringe barrel upward against the needle forcing the needle into the catcher where it locks in place (an audible “click” is heard when the needle is locked in the catcher). The needle is bent until the syringe exceeds a 45 degree angle with the flat surface to render it permanently unusable.
• The syringe is properly disposed of normally.