Dalteparin

Uses

Prophylaxis of clotting in extracorporeal circulation in haemodialysis or haemofiltration, Prophylaxis of clotting in extracorporeal circulation in haemodialysis or haemofiltration, Unstable angina, Prophylaxis of venous thromboembolism during surgical procedures, Venous thromboembolism

Dalteparin is also used to associated treatment for these conditions: Cardiovascular Events, Clotting, Deep Vein Thrombosis, Symptomatic Venous Thromboembolism, Venous Thromboembolism

How Dalteparin works

Dalteparin potentiates the activity of ATIII, inhibiting the formation of both factor Xa and thrombin. The main difference between dalteparin and unfractionated heparin (UH) is that dalteparin preferentially inactivates factor Xa. As a result, only a slight increase in clotting time [(i.e. activated partial thomboplastin time (APTT)] is observed relative to UH. For this same reason, APTT is not used to monitor the effects of dalteparin except as an indicator for overdosage.

Dosage

Dalteparin dosage

Intravenous-

Prophylaxis of clotting in extracorporeal circulation in haemodialysis or haemofiltration: 30-40 U/kg IV inj, then 10-15 U/kg/hr as IV infusion.

Subcutaneous-

Venous thromboembolism: 200 U/kg/day as a single or in 2 divided doses in pregnant and high-risk patients. Max: 18,000 U/day.

Prophylaxis of venous thromboembolism during surgical procedures Moderate risk: 2,500 U given 1-2 hr pre-op then 2,500 U once daily for 5-7 days or until the patient is fully ambulant. High risk: 2,500 U given 1-2 hr before and 8-12 hr after the procedure then 5,000 U daily.

Unstable angina: 120 U/kg 12 hrly continued for 5-8 days w/ low-dose aspirin. Max: 10,000 U 12 hrly.

Side Effects

Elevated serum transaminase levels (AST and ALT), allergic reactions (e.g. pruritus, rash, fever, inj site reaction, bullous eruption), pain on inj site. Epidural or spinal haematomas that may result in permanent paralysis, severe haemorrhage, thrombocytopenia.

Toxicity

Overdosage: hemorrhagic complications. Adverse Drug Reaction: (common) osteopenia with extended use; mild, reversible non-immunological thrombocytopenia; transient elevation of liver transaminases; alopecia. (uncommon): severe immunologically-mediated heparin-induced thrombocytopenia; anaphylactic reactions; skin rash, skin necrosis; retroperitoneal hemorrhage; angioedema

Precaution

Patient with increased risk of bleeding complications (e.g. following surgery or trauma, haemorrhagic stroke, thrombocytopenia or defective platelet function, uncontrolled HTN, hypertensive or diabetic retinopathy). Increased risk of spinal or epidural haematomas in patient undergoing neuraxial anaesth or spinal puncture esp with post-op use of indwelling epidural catheters. Hepatic and renal impairment. Pregnancy and lactation.

Interaction

Increased risk of haemorrhage with other anticoagulant/ antiplatelet agents (e.g. aspirin/ dipyridamole, glycoprotein IIb/ IIIa receptor antagonists, vit K antagonists, NSAIDs, cytostatics, dextran, thrombolytics, sulfinpyrazone, probenecid, etacrynic acid). Reduced anticoagulant effect with antihistamines, cardiac glycosides, tetracycline and ascorbic acid.

Food Interaction

• Avoid herbs and supplements with anticoagulant/antiplatelet activity. Examples include garlic, ginger, bilberry, danshen, piracetam, and ginkgo biloba.

Dalteparin Hypertension interaction

[Major] Heparin should be used with extreme caution in patients with uncontrolled or severe hypertension as these conditions may predispose the patient to hemorrhage during heparin administration.

Blood coagulation tests (e.g., whole blood clotting time, activated partial thromboplastin time) should be performed at appropriate intervals during full-dose heparin administration.

In addition, periodic platelet counts, hematocrits, and tests for occult blood in stool are recommended during the entire course of heparin therapy.

Clinical monitoring of blood pressure is recommended.

[Moderate] Anticoagulants should be used with extreme caution in patients at increased risk for hemorrhage, including those patients with severe hypertension.

Dalteparin Drug Interaction

Major: aspirin, aspirin, clopidogrel, clopidogrelUnknown: ipratropium, ipratropium, glucose, glucose, fentanyl, fentanyl, metronidazole, metronidazole, furosemide, furosemide, acetaminophen, acetaminophen, albuterol, albuterol, cholecalciferol, cholecalciferol

Dalteparin Disease Interaction

Major: hemophilia, liver disease, peptic ulcer disease, retinopathy, subacute bacterial endocarditis, active bleeding, hypertension, renal dysfunction, thrombocytopenia, prematurity, prematurityModerate: hypertension, kidney disease

Volume of Distribution

3 litres

Elimination Route

Almost completely absorbed after subcutaneous (sc) doses, with a bioavialability of about 87%.

Half Life

Terminal Half life: Intravenous - 2 hours. Subcutaneous - 3-5hours

Clearance

Excreted via kidneys. The plasma clearance rate is 33 mL/min.

Elimination Route

After 4 hours, about 20% is seen in urine. Most of the remainder is found in the liver, gastrointestinal tract and kidney. The kidneys are the major site of dalteparin excretion (approximately 70% based on animal studies).

Pregnancy & Breastfeeding use

Pregnancy Category B. Either animal-reproduction studies have not demonstrated a foetal risk but there are no controlled studies in pregnant women or animal-reproduction studies have shown an adverse effect (other than a decrease in fertility) that was not confirmed in controlled studies in women in the 1st trimester (and there is no evidence of a risk in later trimesters).

Contraindication

Hypersensitivity. Active major bleeding, severe coagulation disorders; lumbar puncture; sympathetic block; brain, spinal cord, eye or ear surgery; severe hypertension

Acute Overdose

Symptoms: Haemorrhagic complications.

Management: Administer protamine sulfate by slow IV inj at a dose of 1 mg for every 100 anti-Xa U of dalteparin Na given.

Storage Condition

Store between 20-25°C.

Innovators Monograph

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