dalteparin sodium
Fragmin

Available forms
Available by prescription only
Injection: 2,500 anti-factor Xa IU/0.2 ml (16 mg/ 0.2 ml), 5,000 anti-factor Xa IU/0.2 ml (32 mg/ 0.2 ml); 10,000 IU (64 mg/ml)/9.5 ml multidose vial

Indications and dosages
 Prophylaxis against deep vein thrombosis (DVT) in patients undergoing abdominal surgery who are at risk for thromboembolic complications (including those who are older than age 40, obese, undergoing general anesthesia lasting longer than 30 minutes, and with history of DVT or pulmonary embolism). Adults: 2,500 IU S.C. daily, starting 1 to 2 hours before surgery and repeated once daily for 5 to 10 days postoperatively. In abdominal surgery patients at high risk for thromboembolic complications (such as those with malignant disease), 5,000 IU S.C. daily starting on the evening before surgery and repeated once daily for 5 to 10 days postoperatively. Or, 2500 IU S.C. within 1 to 2 hours before surgery, followed 12 hours later by a second dose of 2,500 IU S.C. and then 5,000 IU S.C. once daily for 5 to 10 days postoperatively.
 Prophylaxis of DVT in patients undergoing hip replacement surgery. Adults: 2,500 IU S.C. within 2 hours before surgery and second dose 2,500 IU S.C. in the evening of surgery (at least 6 hours after first dose). If surgery is performed in the evening, omit second dose on day of surgery. Starting on first postoperative day, administer 5,000 IU S.C. once daily for 5 to 10 days. Or, 5,000 IU S.C. on the evening before surgery, followed by 5,000 IU S.C. once daily starting in the evening of surgery for 5 to 10 days postoperatively.
 To prevent ischemic complications in patients with unstable angina or non-Q-wave MI who are receiving concomitant aspirin therapy. Adults: 120 IU/kg S.C. q 12 hours with concurrent oral aspirin of 75 to 165 mg/day. Continue until patient is stable, usually 5 to 8 days. Don’t exceed 10,000 IU/dose.

Pharmacodynamics
Anticoagulant action: Acts by enhancing the inhibition of factor Xa and thrombin by antithrombin.

Pharmacokinetics
Absorption: Absolute bioavailability measured in anti-factor Xa activity is about 87%.
Distribution: Volume of distribution for dalteparin anti-factor Xa activity is 40 to 60 ml/kg.
Metabolism: Unknown.
Excretion: Unknown.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug, heparin, or pork products and in those with active major bleeding or thrombocytopenia with positive in vitro tests for antiplatelet antibody in the presence of drug.
  Use with extreme caution in patients with a history of heparin-induced thrombocytopenia and in those with increased risk of hemorrhage, such as those with severe uncontrolled hypertension, bacterial endocarditis, congenital or acquired bleeding disorders, active ulceration, angiodysplastic GI disease, or hemorrhagic CVA. Also use cautiously if patient has had recent brain, spinal, or ophthalmic surgery or if patient has bleeding diathesis, thrombocytopenia, platelet defects, severe liver or kidney insufficiency, hypertensive or diabetic retinopathy, or recent GI bleeding.
 Multidose vial contains benzyl alcohol, which has been associated with fatal "gasping syndrome" in premature infants. Benzyl alcohol may cross the placental barrier; therefore, avoid in pregnancy.

Interactions
Drug-drug. Oral anticoagulants, platelet inhibitors: May increase risk of bleeding. Use together cautiously.

Adverse reactions
CNS: fever.
CV: hemorrhage.
Hematologic: thrombocytopenia, bleeding complications.
Skin: pruritus, rash, hematoma, injection site reaction, ecchymoses.

Effects on lab test results
• May increase ALT and AST levels.
• May decrease platelet count.

Overdose and treatment
Overdose may cause hemorrhagic complications.
 Usually, they may be stopped by slow I.V. injection of protamine sulfate (1% solution), at a dose of 1 mg protamine for every 100 anti-factor Xa IU of dalteparin given. A second infusion of 0.5 mg protamine sulfate per 100 anti-factor Xa IU of dalteparin may be administered if the activated partial thromboplastin time (aPTT) measured 2 to 4 hours after the first infusion remains prolonged. Even with these additional doses of protamine sulfate, the aPTT may remain more prolonged than would usually be found following administration of conventional heparin. Protamine may cause hypotension and anaphylactoid reactions. Monitor patient closely.

Special considerations
 ALERT Don’t give drug I.M.
 ALERT Drug isn’t interchangeable (unit for unit) with unfractionated heparin or other low-molecular-weight heparins.
 ALERT Prescribing, dispensing, and dosing errors have been reported using the abbreviation IU. Take care to write clearly or spell out if possible.
• Patients receiving dalteparin who need neuraxial anesthesia or spinal puncture may be at increased risk for an epidural or spinal hematoma, which can result in long-term or permanent paralysis.
• Don’t mix drug with other injections or infusions unless specific compatibility data are available that support such mixing.
• Patient should assume a sitting or lying position when drug is administered. Inject dalteparin S.C. deeply. Injection sites include a U-shaped area around the navel, the upper outer side of the thigh, or the upper outer quadrangle of the buttock. Rotate sites daily. When the area around the navel or the thigh is used, use the thumb and forefinger to lift up a fold of skin while the injection is being given. Insert entire length of needle at a 45- to 90-degree angle.
• Periodic CBC (including platelet count) and stool occult blood tests are recommended in patients receiving dalteparin. Patients don’t need regular monitoring of PT, INR, or aPTT.
• Monitor patient closely for thrombocytopenia.
• Stop drug if a thromboembolic event occurs despite dalteparin prophylaxis.
Breast-feeding patients
• It isn’t known whether drug appears in breast milk; use cautiously in breast-feeding women.
Pediatric patients
• Safety and effectiveness in children haven’t been established.

Patient education
• Tell patient that injection sites include navel, upper thigh, and buttocks and that injection site needs to be changed daily.
• Instruct patient and his family to watch for evidence of bleeding and to report them immediately.
• Tell patient to avoid OTC drugs containing aspirin or other salicylates unless he has medical approval.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use