Drug Detail:Fragmin (Dalteparin [ dal-te-par-in ])
Generic Name: DALTEPARIN SODIUM 2500[iU] in 0.2mL
Dosage Form: injection
Drug Class: Heparins
Recommended Dosage for 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 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 1 lists the volume of FRAGMIN in mL (based on the 3.8 mL multiple-dose vial 25,000 IU/mL) and quantity of FRAGMIN in IU, to be administered for a range of patient weights.
| Patient weight (lb) | <110 | 110 to 131 | 132 to 153 | 154 to 175 | 176 to 197 | ≥198 |
| Patient weight (kg) | <50 | 50 to 59 | 60 to 69 | 70 to 79 | 80 to 89 | ≥90 |
| Quantity of FRAGMIN (IU) | 5,500 IU | 6,500 IU | 7,500 IU | 9,000 IU | 10,000 IU | 10,000 IU |
| Volume of FRAGMIN (mL) 95,000 IU / 3.8 mL |
0.22 | 0.26 | 0.30 | 0.36 | 0.40 | 0.40 |
Prophylaxis of Deep Vein Thrombosis
Prophylaxis of VTE Following Hip Replacement Surgery: Table 2 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.
| Timing of First Dose of FRAGMIN | Dose of FRAGMIN to be Given Subcutaneously | |||
|---|---|---|---|---|
| 10 to 14 Hours Before Surgery | Within 2 Hours Before Surgery | 4 to 8 Hours After Surgery* | Postoperative Period† | |
|
||||
| Postoperative Start | --- | --- | 2,500 IU‡ | 5,000 IU once daily |
| Preoperative Start - Day of Surgery | --- | 2,500 IU | 2,500 IU‡ | 5,000 IU once daily |
| Preoperative Start - Evening Before Surgery§ | 5,000 IU | --- | 5,000 IU | 5,000 IU once daily |
Abdominal Surgery: In patients undergoing abdominal surgery with a risk of thromboembolic complications, the recommended dose of FRAGMIN is 2,500 IU administered by subcutaneous 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 5,000 IU subcutaneously the evening before surgery, then once daily postoperatively. The usual duration of administration is 5 to 10 days. Alternatively, in patients with malignancy, 2,500 IU of FRAGMIN can be administered subcutaneously 1 to 2 hours before surgery followed by 2,500 IU subcutaneously 12 hours later, and then 5,000 IU once daily postoperatively. The usual duration of administration is 5 to 10 days.
Extended Treatment of Symptomatic Venous Thromboembolism (VTE) in Adult Patients with Cancer
In adult patients with cancer and symptomatic VTE, the recommended dosing of FRAGMIN is as follows: for the first 30 days of treatment administer FRAGMIN 200 IU/kg total body weight subcutaneously once daily. The total daily dose should not exceed 18,000 IU. Table 3 lists the dose of FRAGMIN to be administered once daily during the first month for a range of patient weights.
Month 1
| Body Weight (lbs) | Body Weight (kg) | FRAGMIN Dose (IU) (prefilled syringe) once daily |
|---|---|---|
| ≤124 | ≤56 | 10,000 |
| 125 to 150 | 57 to 68 | 12,500 |
| 151 to 181 | 69 to 82 | 15,000 |
| 182 to 216 | 83 to 98 | 18,000 |
| ≥217 | ≥99 | 18,000 |
Months 2 to 6
Administer FRAGMIN at a dose of approximately 150 IU/kg, subcutaneously once daily during Months 2 through 6. The total daily dose should not exceed 18,000 IU. Table 4 lists the dose of FRAGMIN to be administered once daily for a range of patient weights during months 2–6.
| Body Weight (lbs) | Body Weight (kg) | FRAGMIN Dose (IU) (prefilled syringe) once daily |
|---|---|---|
| ≤124 | ≤56 | 7,500 |
| 125 to 150 | 57 to 68 | 10,000 |
| 151 to 181 | 69 to 82 | 12,500 |
| 182 to 216 | 83 to 98 | 15,000 |
| ≥217 | ≥99 | 18,000 |
Safety and efficacy beyond six months have not been evaluated in patients with cancer and acute symptomatic VTE [see Warnings and Precaution (5) and Adverse Reactions (6.1)].
Treatment of Symptomatic Venous Thromboembolism (VTE) in Pediatric Patients
The recommended starting dose according to pediatric age is provided in Table 5.
| Age Group | Starting Dose |
|---|---|
| 4 Weeks to less than 2 Years | 150 IU/kg twice daily |
| 2 Years to less than 8 Years | 125 IU/kg twice daily |
| 8 Years to less than 17 Years | 100 IU/kg twice daily |
After initiation of FRAGMIN, measure anti-Xa level prior to the 4th dose. Samples for anti-Xa level should be drawn 4 hours after administration of FRAGMIN. Adjust doses in increments of 25 IU/kg to achieve target anti-Xa level between 0.5 and 1 IU/mL. Individualize the maintenance dose of FRAGMIN based on the dose that achieves target anti-Xa level collected 4 hours after administration of FRAGMIN. Monitor anti-Xa level periodically in pediatric patients to maintain anti-Xa level between 0.5 and 1 IU/mL [see Clinical Pharmacology (12.3) and Clinical Studies (14.5)].
Whenever possible, administer benzyl alcohol-free formulations (prefilled syringes) in pediatric patients [see Warnings and Precautions (5.3) and Use in Specific Populations (8.4)].
Dose Reductions for Thrombocytopenia in Adult Patients with Cancer and in Pediatric Patients with Symptomatic VTE
Dose reductions recommended in patients receiving FRAGMIN who experience thrombocytopenia are presented below in Table 6.
| Platelet Count less than or equal to 50,000/mm3 | Platelet Count equal to 50,000 to 100,000/mm3 | |
|---|---|---|
| Adults | Discontinue FRAGMIN until platelet count recovers to above 50,000/mm3. | Reduce the daily dose of FRAGMIN by 2,500 IU until the platelet count recovers to greater or equal to 100,000/mm3. |
| Children 4 Weeks to less than 17 Years | Discontinue FRAGMIN until platelet count recovers to above 50,000/mm3. | Reduce the daily dose of FRAGMIN by 50% until the platelet count recovers to greater or equal to 100,000/mm3. |
Dose Reductions for Renal Insufficiency in Extended Treatment of Acute Symptomatic VTE in Adult Patients with Cancer
In patients with severely impaired renal function (CrCl <30 mL/min), monitor anti-Xa levels to determine the appropriate FRAGMIN dose. Target anti-Xa range is 0.5–1.5 IU/mL. When monitoring anti-Xa in these patients, perform sampling 4–6 hours after FRAGMIN dosing and only after the patient has received 3–4 doses.
Administration
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.
FRAGMIN is administered by subcutaneous injection. It must not be administered by intramuscular injection.
FRAGMIN Injection should not be mixed with other injections or infusions unless specific compatibility data are available that support such mixing.
Subcutaneous injection technique: Patients should be sitting or lying down and FRAGMIN administered by deep subcutaneous 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.
Inspect FRAGMIN prefilled syringes and vials visually for particulate matter and discoloration prior to administration
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.
