FRAGMIN Injection is indicated for the prophylaxis of ischemic complications in unstable angina and non-Q-wave myocardial infarction, when concurrently administered with aspirin therapy (as described in CLINICAL TRIALS, Prophylaxis of Ischemic Complications in Unstable Angina and Non-Q-Wave Myocardial Infarction).

FRAGMIN is also indicated for the prophylaxis of deep vein thrombosis (DVT), which may lead to pulmonary embolism (PE):

• In patients undergoing hip replacement surgery;
• In patients undergoing abdominal surgery who are at risk for thromboembolic complications;
• In medical patients who are at risk for thromboembolic complications due to severely restricted mobility during acute illness.

FRAGMIN is also indicated for the extended treatment of symptomatic venous thromboembolism (VTE) (proximal DVT and/or PE), to reduce the recurrence of VTE in patients with cancer.

Prophylaxis of Ischemic Complications in Unstable Angina and Non-Q-Wave Myocardial Infarction

In patients with unstable angina or non-Q-wave myocardial infarction, the recommended dose of FRAGMIN Injection is 120 IU/kg of body weight, but not more than 10,000 IU, subcutaneously (s.c.) every 12 hours with concurrent oral aspirin (75 to 165 mg once daily) therapy. Treatment should be continued until the patient is clinically stabilized. The usual duration of administration is 5 to 8 days. Concurrent aspirin therapy is recommended except when contraindicated.

Table 13 lists the volume of FRAGMIN, based on the 9.5 mL multiple-dose vial (10,000 IU/mL), to be administered for a range of patient weights.

Table 13
Volume of FRAGMIN to be Administered by Patient Weight, Based on 9.5 mL Vial (10,000 IU/mL)

Prophylaxis of Venous Thromboembolism Following Hip Replacement Surgery

Table 14 presents the dosing options for patients undergoing hip replacement surgery. The usual duration of administration is 5 to 10 days after surgery; up to 14 days of treatment with FRAGMIN have been well tolerated in clinical trials.

Table 14
Dosing Options for Patients Undergoing Hip Replacement Surgery

Prophylaxis of Venous Thromboembolism Following Abdominal Surgery

In patients undergoing abdominal surgery with a risk of thromboembolic complications, the recommended dose of FRAGMIN is 2500 IU administered by s.c. injection once daily, starting 1 to 2 hours prior to surgery and repeated once daily postoperatively. The usual duration of administration is 5 to 10 days.

In patients undergoing abdominal surgery associated with a high risk of thromboembolic complications, such as malignant disorder, the recommended dose of FRAGMIN is 5000 IU s.c. the evening before surgery, then once daily postoperatively. The usual duration of administration is 5 to 10 days. Alternatively, in patients with malignancy, 2500 IU of FRAGMIN can be administered s.c. 1 to 2 hours before surgery followed by 2500 IU s.c. 12 hours later, and then 5000 IU once daily postoperatively. The usual duration of administration is 5 to 10 days.

Dosage adjustment and routine monitoring of coagulation parameters are not required if the dosage and administration recommendations specified above are followed.

Medical Patients with Severely Restricted Mobility During Acute Illness

In medical patients with severely restricted mobility during acute illness, the recommended dose of FRAGMIN is 5000 IU administered by s.c. injection once daily. In clinical trials, the usual duration of administration was 12 to 14 days.

Extended Treatment of Symptomatic Venous Thromboembolism in Patients with Cancer

In patients with cancer and symptomatic venous thromboembolism, the recommended dosing of FRAGMIN is as follows: for the first 30 days of treatment administer FRAGMIN 200 IU/kg total body weight subcutaneously (s.c.) once daily. The total daily dose should not exceed 18,000 IU. Table 15 lists the dose of FRAGMIN to be administered once daily during the first month for a range of patient weights.

Month 1

Table 15
Dose of FRAGMIN to be Administered Subcutaneously by Patient Weight during the First Month

Months 2 to 6

Administer FRAGMIN at a dose of approximately 150 IU/kg, s.c. once daily during Months 2 through 6. The total daily dose should not exceed 18,000 IU. Table 16 lists the dose of FRAGMIN to be administered once daily for a range of patient weights during months 2-6.

Table 16
Dose of FRAGMIN to be Administered Subcutaneously by Patient Weight duringMonths 2-6

Safety and efficacy beyond six months have not been evaluated in patients with cancer and acute symptomatic VTE (see WARNINGS, Thrombocytopenia and ADVERSE REACTIONS, Patients with Cancer and Acute Symptomatic VTE).

Dose reductions for thrombocytopenia in patients with cancer and acute symptomatic VTE

In patients receiving FRAGMIN who experience platelet counts between 50,000 and 100,000/mm3, reduce the daily dose of FRAGMIN 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/mm^3.

Dose reductions for renal insufficiency in extended treatment of acute symptomatic venous thromboembolism in patients with cancer

In patients with severely impaired renal function (CrCl ≤ 30 mL/min), monitoring for anti-Xa levels is recommended to determine the appropriate FRAGMIN dose. Target anti-Xa range is 0.5-1.5 IU/mL. When monitoring anti-Xa in these patients, sampling should be performed 4-6 hrs after FRAGMIN dosing and only after the patient has received 3-4 doses.

Administration

FRAGMIN is administered by subcutaneous injection. It must not be administered by intramuscular injection.

Subcutaneous injection technique: Patients should be sitting or lying down and FRAGMIN administered by deep s.c. injection. FRAGMIN 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.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

After first penetration of the rubber stopper, store the multiple-dose vials at room temperature for up to 2 weeks. Discard any unused solution after 2 weeks.

Instructions for using the prefilled single-dose syringes preassembled with needle guard devices

Fixed dose syringes: To ensure delivery of the full dose, do not expel the air bubble from the prefilled syringe before injection. Hold the syringe assembly by the open sides of the device. Remove the needle shield. Insert the needle into the injection area as instructed above. Depress the plunger of the syringe while holding the finger flange until the entire dose has been given. The needle guard will not be activated unless the entire dose has been given. Remove needle from the patient. Let go of the plunger and allow syringe to move up inside the device until the entire needle is guarded. Discard the syringe assembly in approved containers.

Graduated syringes: Hold the syringe assembly by the open sides of the device. Remove the needle shield. With the needle pointing up, prepare the syringe by expelling the air bubble and then continuing to push the plunger to the desired dose or volume, discarding the extra solution in an appropriate manner. Insert the needle into the injection area as instructed above. Depress the plunger of the syringe while holding the finger flange until the entire dose remaining in the syringe has been given. The needle guard will not be activated unless the entire dose has been given. Remove needle from the patient. Let go of the plunger and allow syringe to move up inside the device until the entire needle is guarded. Discard the syringe assembly in approved containers.

FRAGMIN Injection is available in the following strengths and package sizes:

Store at controlled room temperature 20° to 25°C (68° to 77°F) [see USP] .

Fragmin is a registered trademark of Pfizer Health AB and is licensed to Eisai Inc.
* UltraSafe Passive™ Needle Guard is a trademark of Safety Syringes, Inc.

Manufactured for: Eisai Inc.Tbr /Teaneck, NJ 07666
Manufactured by: Pfizer Inc., New York, NY 10017
Made in Belgium (multiple-dose vials)
Jointly manufactured by: Pfizer Inc, New York, NY 10017
and Vetter Pharma-Fertigung, GmbH & Co. KG., Ravensburg, Germany
(prefilled syringes)
FDA rev date: 5/1/2007

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