Fragmin: Package Insert and Label Information

FRAGMIN- dalteparin sodium injection
Eisai Inc.

WARNING: SPINAL/EPIDURAL HEMATOMAS

Epidural or spinal hematomas may occur in patients who are anticoagulated with low molecular weight heparins (LMWH) or heparinoids and are receiving neuraxial anesthesia or undergoing spinal puncture. These hematomas may result in long-term or permanent paralysis. Consider these risks when scheduling patients for spinal procedures. Factors that can increase the risk of developing epidural or spinal hematomas in these patients include:

  • Use of indwelling epidural catheters
  • Concomitant use of other drugs that affect hemostasis, such as non-steroidal anti-inflammatory drugs (NSAIDs), platelet inhibitors, other anticoagulants.
  • A history of traumatic or repeated epidural or spinal punctures
  • A history of spinal deformity or spinal surgery
  • Optimal timing between the administration of FRAGMIN and neuraxial procedures is not known

Monitor patients frequently for signs and symptoms of neurological impairment. If neurological compromise is noted, urgent treatment is necessary.

Consider the benefits and risks before neuraxial intervention in patients anticoagulated or to be anticoagulated for thromboprophylaxis [see Warnings and Precautions (5.1) and Drug Interactions (7) ].

1 INDICATIONS AND USAGE

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

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 [see Clinical Studies (14.1) ].

1.2 Prophylaxis of Deep Vein Thrombosis

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 [see Clinical Studies (14.2) ];
  • In patients undergoing abdominal surgery who are at risk for thromboembolic complications [see Clinical Studies (14.3) ];
  • In medical patients who are at risk for thromboembolic complications due to severely restricted mobility during acute illness [see Clinical Studies (14.4) ].

1.3 Extended Treatment of Symptomatic Venous Thromboembolism in Patients with Cancer

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. In these patients, the FRAGMIN therapy begins with the initial VTE treatment and continues for six months [see Clinical Studies (14.5) ].

Limitations of Use FRAGMIN is not indicated for the acute treatment of VTE.

2 DOSAGE AND ADMINISTRATION

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.

Routine coagulation tests such as Prothrombin Time (PT) and Activated Partial Thromboplastin Time (APTT) are relatively insensitive measures of FRAGMIN activity and, therefore, unsuitable for monitoring the anticoagulant effect of FRAGMIN. [see Warnings and Precautions ( 5) ].

2.1 Adult Dosage

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

Table 1
Volume of FRAGMIN to be Administered by Patient Weight, Based on 9.5 mL Vial (10,000 IU/mL)
Patientweight (lb) < 110 110 to 131 132 to 153 154 to 175 176 to 197 ≥ 198
Patientweight (kg) < 50 50 to 59 60 to 69 70 to 79 80 to 89 ≥ 90
Volume ofFRAGMIN (mL) 0.55 0.65 0.75 0.90 1.0 1.0

Prophylaxis of Venous Thromboembolism 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.

Table 2
Dosing Options for Patients Undergoing Hip Replacement Surgery
Timing of First Dose of FRAGMIN Dose of FRAGMIN to be Given Subcutaneously
10 to 14 HoursBefore Surgery Within 2 HoursBefore Surgery 4 to 8 HoursAfter Surgery1 PostoperativePeriod2
Postoperative Start 2500 IU3 5000 IU once daily
Preoperative Start — Day of Surgery 2500 IU 2500 IU3 5000 IU once daily
Preoperative Start — Evening Before Surgery4 5000 IU 5000 IU 5000 IU once daily

1 Or later, if hemostasis has not been achieved.
2 Up to 14 days of treatment was well tolerated in controlled clinical trials, where the usual duration of treatment was 5 to 10 days postoperatively.
3 Allow a minimum of 6 hours between this dose and the dose to be given on Postoperative Day 1. Adjust the timing of the dose on Postoperative Day 1 accordingly.4 Allow approximately 24 hours between doses.

Abdominal Surgery: In patients undergoing abdominal surgery with a risk of thromboembolic complications, the recommended dose of FRAGMIN is 2500 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 5000 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, 2500 IU of FRAGMIN can be administered subcutaneously 1 to 2 hours before surgery followed by 2500 IU subcutaneously 12 hours later, and then 5000 IU once daily postoperatively. The usual duration of administration is 5 to 10 days.

Medical Patients During Acute Illness: In medical patients with severely restricted mobility during acute illness, the recommended dose of FRAGMIN is 5000 IU administered by subcutaneous 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 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

Table 3
Dose of FRAGMIN to be Administered Subcutaneously by Patient Weight during the First Month
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.

Table 4
Dose of FRAGMIN to be Administered Subcutaneously by Patient Weight 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) ].

2.2 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 , discontinue FRAGMIN until the platelet count recovers above 50,000/mm3.

2.3 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), 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 hrs after FRAGMIN dosing and only after the patient has received 3-4 doses.

2.4 Administration

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

fragmin-01
(click image for full-size original)

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.

DrugInserts.com provides trustworthy package insert and label information about marketed drugs as submitted by manufacturers to the US Food and Drug Administration. Package information is not reviewed or updated separately by DrugInserts.com. Every individual package label entry contains a unique identifier which can be used to secure further details directly from the US National Institutes of Health and/or the FDA.

As the leading independent provider of trustworthy medication information, we source our database directly from the FDA's central repository of drug labels and package inserts under the Structured Product Labeling standard. Our material is not intended as a substitute for direct consultation with a qualified health professional.

Terms of Use | Copyright © 2020. All Rights Reserved.