Dalteparin Sodium

Pronunciation: (DAL-te-PAR-in SOE-dee-um)
Class: Low molecular weight heparin (LMWH)

Trade Names

Fragmin
- Injection, solution 2,500 units (dalteparin sodium 16 mg per 0.2 mL) in prefilled syringes
- Injection, solution 5,000 units (dalteparin sodium 32 mg per 0.2 mL) in prefilled syringes
- Injection, solution 7,500 units (dalteparin sodium 48 mg per 0.3 mL) in prefilled syringes
- Injection, solution 10,000 units (dalteparin sodium 64 mg per mL) in prefilled syringes
- Injection, solution 12,500 units (dalteparin sodium 80 mg per 0.5 mL) in prefilled syringes
- Injection, solution 15,000 units (dalteparin sodium 96 mg per 0.6 mL) in prefilled syringes
- Injection, solution 18,000 units (dalteparin sodium 115.2 mg per 0.72 mL) in prefilled syringes
- Injection, solution 10,000 units (dalteparin sodium 64 mg/mL) in graduated prefilled syringes
- Injection, solution 95,000 units per 3.8 mL (dalteparin sodium 160 mg/mL) in multiple-dose vials
- Injection, solution 95,000 units per 9.5 mL (dalteparin sodium 64 mg/mL) in multiple-dose vials

Pharmacology

Inhibits reactions that lead to clotting.

Pharmacokinetics

Absorption

Bioavailability is approximately 87%.

T _max is approximately 4 h.

Distribution

Vd is 40 to 60 mL/kg.

Elimination

Subcutaneous

The half-life is 3 to 5 h.

Special Populations

Renal Function Impairment

Mean terminal half-life was prolonged to 5.7 h following IV administration to patients with chronic renal insufficiency requiring hemodialysis; greater accumulation can be expected in these patients.

Indications and Usage

Prophylaxis of ischemic complications in unstable angina and non–Q-wave MI in patients on aspirin therapy; prophylaxis of deep vein thrombosis (DVT), which may lead to pulmonary embolism, in patients undergoing hip replacement surgery, in patients undergoing abdominal surgery who are at risk for thromboembolic complications, or in patients who are at risk of thromboembolic complications due to severely restricted mobility during acute illness; extended treatment of symptomatic venous thromboembolism (VTE) (proximal DVT and/or pulmonary embolism) to reduce recurrence of VTE in patients with cancer.

Unlabeled Uses

Primary VTE prophylaxis in cancer patients; VTE prophylaxis in cancer patients with central venous catheters; VTE prophylaxis in general or gynecologic surgery.

Contraindications

Active major bleeding; history of heparin-induced thrombocytopenia or heparin-induced thrombocytopenia with thrombosis; as treatment for unstable angina of non–Q-wave MI or prolonged VTE prophylaxis in patients undergoing epidural/neuraxial anesthesia; hypersensitivity to heparin or pork products or to any component of the product.

Dosage and Administration

Unstable Angina/Non–Q-Wave MI
Adults

Subcutaneous 120 units/kg of body weight (max, 10,000 units) every 12 h with aspirin (75 to 165 mg/day, unless contraindicated) therapy. Continue treatment until patient is clinically stabilized, usually 5 to 8 days.

DVT Prophylaxis (Hip Replacement Surgery)
Adults

Subcutaneous If started postoperatively, 2,500 units within 4 to 8 h after surgery, followed by 5,000 units/day for 5 to 10 days; if started preoperatively on day of surgery, 2,500 units within 2 h before surgery, followed by 2,500 units 4 to 8 h after surgery and continued at 5,000 units/day for 5 to 10 days; if started preoperatively on the evening before surgery, 5,000 units 10 to 14 h before surgery, followed by 5,000 units 4 to 8 h after surgery and continued at 5,000 units/day for 5 to 10 days.

DVT Prophylaxis (Abdominal Surgery)
Adults

Subcutaneous 2,500 units starting 1 to 2 h before surgery and continuing every day for 5 to 10 days. In patients undergoing abdominal surgery with a high risk of complications (eg, malignant disorder), recommended dose is 5,000 units the evening before surgery, then once daily for 5 to 10 days. Alternatively, in patients with malignancy, 2,500 units of dalteparin can be administered 1 to 2 h before surgery followed by 2,500 units 12 h later, and then 5,000 units once daily for 5 to 10 days.

Medical Patients With Severely Restricted Mobility During Acute Illness
Adults

Subcutaneous 5,000 units/day for 12 to 14 days.

Extended Treatment of Symptomatic Venous Thromboembolism in Cancer Patients
Adults

Subcutaneous For the first 30 days of treatment, give 200 units/kg once daily (max, 18,000 units/day). Months 2 to 6: Administer 150 units/kg once daily (max, 18,000 units/day).

Dose reductions for thrombocytopenia

In patients with platelet counts between 50,000 and 100,000/mm ³ , reduce the daily dose by 2,500 units until platelet count recovers to at least 100,000 units/mm ³ . In patients who experience platelet counts below 50,000 units/mm ³ , discontinue dalteparin until platelet count recovers to 50,000 units/mm ³ .

Dose reductions for renal impairment

In patients with severe renal impairment (CrCl less than 30 mL/min), monitor for anti-Xa levels to determine dalteparin dose. Target anti-Xa range is 0.5 to 1.5 units/mL. Sampling should be performed 4 to 6 h after dosing and only after 3 to 4 doses have been given.

General Advice

Do not administer by IM injection.
Vary injection site daily. Dalteparin 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.
Do not mix with other injections or infusions until compatibility is determined.
Inspect all preparations for particulate matter prior to administration.

Storage/Stability

Store at 68° to 77°F. After first penetration of the rubber stopper, store the multidose vial at room temperature for up to 2 weeks.

Drug Interactions

Anticoagulants (eg, warfarin), platelet inhibitors (eg, clopidogrel, dipyridamole, NSAIDs, salicylates, ticlopidine), thrombolytic agents (eg, tenecteplase)

Increased risk of bleeding.

Antithrombin

The risk of severe bleeding may be increased. Close clinical and laboratory monitoring (aPTT and/or anti-Xa) is indicated during coadministration of dalteparin and antithrombin. Adjust the dose of dalteparin accordingly. Reduced doses of dalteparin are recommended when coadministered with antithrombin III.

SSRIs (eg, fluoxetine)

The risk of severe bleeding may be increased. Carefully monitor the coagulation status of the patient and observe the patient for bleeding. Adjust therapy as needed.

Laboratory Test Interactions

Aminotransferase (AST and ALT)

Dalteparin caused increased concentrations.

Adverse Reactions

Dermatologic

Alopecia, skin necrosis (postmarketing).

Genitourinary

Hematuria (3%).

Hematologic-Lymphatic

Any bleeding event (14%); major bleeding events (6%); epidural or spinal hematoma (postmarketing).

Hypersensitivity

Allergic reactions, including pruritus, rash, fever, injection-site reaction, or bullous eruption; anaphylactoid reactions.

Lab Tests

ALT elevation (14%); AST elevation (12%).

Local

Injection-site hematoma (7%); wound hematoma (3%); injection-site pain (at least 2%).

Precautions

Warnings

Spinal/Epidural hematomas

Risk of spinal/epidural hematoma, which can result in long-term or permanent paralysis, is increased in patients receiving neuraxial anesthesia or spinal puncture who are anticoagulated with LMWHs or heparinoids. Other risk factors include indwelling epidural catheters, repeated/traumatic epidural/spinal puncture, history of spinal deformity or spinal injury, or use of other drugs affecting hemostasis (eg, NSAIDs, platelet inhibitors, anticoagulants). Frequently monitor for signs or symptoms of neurological impairment.

Monitor

Periodic routine CBC, including platelet count, blood chemistry, and stool occult blood tests, is recommended; anticoagulant effect can be monitored by using anti-factor Xa in patients with severe renal impairment or if abnormal coagulation parameters or bleeding occur.

Pregnancy

Category B .

Lactation

Excreted.

Children

Safety and efficacy not established.

Renal Function

Use with caution in patients with severe renal impairment.

Benzyl alcohol

The multiple-dose vial of dalteparin contains benzyl alcohol as a preservative, which has been associated with fatal “gasping syndrome” in premature infants.

Bleeding risk

Avoid use in patients at risk for bleeding (eg, severe hypertension, severe liver or kidney disease, platelet defects, recent GI bleeding) or shortly after brain, spinal, or ophthalmological surgery.

Interchangeability with heparin

Cannot be exchanged on a unit-per-unit basis with other types of heparin.

Thrombocytopenia

Use cautiously in patients with history of heparin-induced thrombocytopenia. Closely monitor thrombocytopenia of any degree.

Overdosage

Symptoms

Hemorrhagic complications.

Patient Information

Inform patients who have had neuraxial anesthesia or spinal puncture, especially if they are taking concomitant NSAIDs, platelet inhibitors, or other anticoagulants, that they should watch for signs and symptoms of spinal or epidural hematoma such as tingling, numbness (especially in the lower limbs), and muscular weakness, and to contact their health care provider immediately if they occur.
Advise patients that the use of aspirin and other NSAIDs may enhance the risk of hemorrhage.
Instruct patient to report any signs of bleeding or bruising, signs of thrombocytopenia (eg, a rash of dark spots under the skin), or black, bloody, or tarry stools immediately.
If patient has home therapy, teach patient or family member proper subcutaneous injection technique.
Caution patient to take safety precautions to prevent cuts and bruising (eg, use electric razor, soft toothbrush, and handrails).
Advise patients to inform their health care providers and dentists that they are taking dalteparin or any other product known to affect bleeding before any surgery is scheduled or before any new drug is taken.