FRAGMIN INJECTION 2500 IU/ML [SIN05249P]

Product Info

FRAGMIN INJECTION 2500 IU/ML

[SIN05249P]

4.1. Therapeutic indications

1. Treatment of acute deep vein thrombosis (DVT)

2. Prevention of clotting in the extracorporeal system during hemodialysis and hemofiltration in patients with acute renal failure or chronic renal insufficiency

3. Thromboprophylaxis in conjunction with surgery

4. The prophylaxis of proximal DVT in patients bedridden due to a medical condition, including, but not limited to: congestive cardiac failure, acute respiratory failure or acute infection, who also have a predisposing risk factor for venous thromboembolism such as age over 75 years, obesity, cancer or previous history of VTE

5. Unstable coronary artery disease (unstable angina and non-ST-elevation myocardial infarction, also known as non-Q-wave myocardial infarction)

Dalteparin should not be used in patients who have suffered a recent (within 3 months) stroke unless due to systemic emboli.

4.2. Posology and method of administration

See section 4.4. Special warnings and precautions for use – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information.

General

Do not administer dalteparin by the intramuscular route.

Dalteparin is administered by subcutaneous injection for all indications except for the prevention of clotting in the extracorporeal system during hemodialysis and hemofiltration where it is administered either intravenously or into the arterial side of the dialyzer.

Compatibility with Intravenous (IV) Solutions

Dalteparin is compatible with isotonic sodium chloride (9 mg/mL) or isotonic glucose (50 mg/mL) infusion solution in glass bottles and plastic containers.

The solution should be used within 12 hours.

1. Treatment of Acute DVT

   Administer dalteparin subcutaneously (SC) either as a single daily injection or as two daily injections. Simultaneous anticoagulation with oral vitamin K antagonists can be started immediately. Continue combined treatment until the prothrombin complex tests have reached therapeutic levels (usually at least 5 days). Outpatient treatment is feasible using the same doses recommended for treatment in a medical institution.

   • Once-daily administration - 200 international units/kg total body weight SC once daily, up to a maximum of 18,000 international units. Monitoring of the anticoagulant effect is not necessary.

   • Twice-daily administration - Alternatively, a dose of 100 international units/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 (see section 4.4. Special warnings and precautions for use – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). Samples should be taken during maximum plasma levels (3–4 hours after a SC injection). Recommended peak plasma levels are between 0.5 and 1.0 international units anti-Xa/mL.

2. Prevention of Clotting in the Extracorporeal System During Hemodialysis and Hemofiltration

   Administer dalteparin into the arterial side of the dialyzer or intravenously, selecting the appropriate regimen from those described below.

   • Patients with chronic renal insufficiency or patients with no known risk of bleeding - These patients normally require few dose adjustments and, therefore, frequent monitoring of anti-Xa levels is not necessary for most patients.

     • Hemodialysis and hemofiltration up to a maximum of 4 hours - A single bolus injection of 5,000 international units can be administered, either intravenously or into the arterial side of the extracorporeal system, at the start of the procedure.
       Alternatively, administer 30 to 40 international units/kg total body weight IV bolus injection, followed by 10 to 15 international units/kg/h IV infusion.

       The 5,000 international units starting dose for the single bolus dosing regimen can be adjusted, session-to-session, based on the outcome of the previous dialysis; the dose may be increased or decreased in steps of 500 or 1,000 anti-Xa international units until a satisfactory outcome is obtained (see section 5.1. Pharmacodynamic properties – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

     • Hemodialysis and hemofiltration longer than 4 hours - Administer 30 to 40 international units/kg total body weight IV bolus injection, followed by 10 to 15 international units/kg/h IV infusion.

   • Patients with acute renal failure, or patients with a high risk of bleeding - Administer 5 to 10 international units/kg total body weight as IV bolus injection, followed by 4 to 5 international units/kg/h IV infusion. Patients undergoing acute hemodialysis have a narrower therapeutic range than patients on chronic hemodialysis, and should undergo comprehensive monitoring of anti-Xa levels. Recommended plasma levels are between 0.2 and 0.4 international units anti-Xa/mL.

3. Thromboprophylaxis in Conjunction with Surgery

   Administer dalteparin SC. Monitoring of the anticoagulant effect is generally not necessary. If done, samples should be taken during maximum plasma levels (3–4 hours after an SC injection). Recommended doses usually produce peak plasma levels between 0.1 and 0.4 international units anti-Xa/mL.

   • General surgery - Select the appropriate regimen from those listed below.

   • Patients at risk for thromboembolic complications - Administer 2,500 international units SC within 2 hours before surgery and 2,500 international units SC each postoperative morning until the patient is mobilized (generally 5–7 days or longer).

   • Patients with additional risk factors for thromboembolism (e.g., malignancy) - Administer dalteparin until the patient is mobilized (generally 5–7 days or longer).

     • Start on day before surgery - 5,000 international units SC on the evening before surgery; following surgery, 5,000 international units SC each evening.

     • Start on day of surgery - 2,500 international units SC within 2 hours before surgery and 2,500 international units SC 8 to 12 hours later, but no sooner than 4 hours after the end of surgery; starting on the day after surgery, 5,000 international units SC each morning.

   • Orthopedic surgery (such as hip replacement surgery) - Administer dalteparin for up to 5 weeks after surgery, selecting one of the regimens listed below.

     • Preoperative start: Evening before surgery - 5,000 international units SC on the evening before surgery; following surgery, 5,000 international units SC each evening.

     • Preoperative start: Day of surgery - 2,500 international units SC within 2 hours before surgery and 2,500 international units SC 8 to 12 hours later, but no sooner than 4 hours after the end of surgery; starting on the day after surgery, 5,000 international units SC each morning.

     • Postoperative start - 2,500 international units SC 4 to 8 hours after surgery, but no sooner than 4 hours after the end of surgery; starting on the day after surgery, 5,000 international units SC each day.

4. Thromboprophylaxis in Patients with Restricted Mobility

   Administer 5,000 international units of dalteparin SC once daily, generally for 12 to 14 days or longer in patients with continued restricted mobility. Monitoring of the anticoagulant effect is generally not necessary.

5. Unstable Coronary Artery Disease (Unstable Angina and Non-ST-elevation Myocardial Infarction)

   Administer dalteparin 120 international units/kg total body weight SC every 12 hours up to a maximum dose of 10,000 international units/12 h. Unless specifically contraindicated, patients should also receive concomitant therapy with acetylsalicylic acid (75–325 mg/day). Continue treatment until the patient is clinically stable (generally at least 6 days), or longer if considered of benefit by the physician.

   Monitoring of the anticoagulant effect is generally not necessary but should be considered for specific patient populations (See section 4.4. Special warnings and precautions for use – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). Samples should be taken during maximum plasma levels (3–4 hours after a SC injection). Recommended peak plasma levels are between 0.5 and 1.0 international units anti-Xa/mL.

4.3. Contraindications

Dalteparin should not be used in patients who have:

• Confirmed or suspected history of immunologically mediated heparin-induced thrombocytopenia

• Active, clinically significant bleeding (such as gastrointestinal ulceration or bleeding, or cerebral hemorrhage)

• Severe coagulation disorders

• Acute or sub-acute septic endocarditis

• Recent injury to, or surgical procedures of, the central nervous system, eyes and/or ears

• Hypersensitivity to dalteparin, other low molecular weight heparins (LMWH), heparins, or pork products.

• Because of an increased risk of bleeding, concomitant treatment with high doses of dalteparin (such as those needed to treat acute DVT and unstable coronary artery disease) should not be used in patients who will receive spinal or epidural anesthesia or other procedures requiring spinal puncture (see section 4.4. Special warnings and precautions for use – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).