Usage
Dalteparin is prescribed for the prevention and treatment of venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE). It is also used in patients with unstable angina and in those undergoing hemodialysis to prevent clotting in the extracorporeal circuit. Its pharmacological classification is an anticoagulant, specifically a low molecular weight heparin (LMWH). Dalteparin works by enhancing the activity of antithrombin III, which inhibits coagulation factors Xa and IIa (thrombin), thus preventing clot formation.
Alternate Names
Dalteparin sodium is the generic name. A popular brand name is Fragmin.
How It Works
Pharmacodynamics: Dalteparin primarily acts by accelerating the activity of antithrombin III. This leads to the inactivation of factor Xa and, to a lesser extent, factor IIa (thrombin), thereby suppressing the coagulation cascade and preventing the formation of fibrin clots.
Pharmacokinetics: Dalteparin is administered subcutaneously and has a bioavailability of approximately 90%. Peak anti-Xa activity is reached 3 to 5 hours post-injection. It has a half-life of about 3 to 5 hours, primarily eliminated by renal clearance. Metabolism occurs through depolymerization and desulfation in the liver.
Mode of Action: Dalteparin binds to antithrombin III, causing a conformational change that increases its affinity for factor Xa. This complex irreversibly inhibits factor Xa, interrupting the coagulation cascade. While dalteparin also inhibits thrombin, its effect on Xa is more pronounced.
Elimination Pathways: Dalteparin is mainly excreted via the kidneys as depolymerized and desulfated fragments. Hepatic metabolism also contributes to its elimination.
Dosage
Standard Dosage
Adults:
- VTE Prophylaxis: 2500-5000 IU SC once daily. Higher doses may be used in specific clinical situations (e.g. post-surgery).
- VTE Treatment: 200 IU/kg SC once daily or 100 IU/kg SC every 12 hours. Maximum dose is usually 18,000 IU/day.
- Unstable Angina/Non-ST-Segment Elevation MI: 120 IU/kg SC every 12 hours (maximum 10,000 IU per dose) with concurrent aspirin.
Children:
- VTE Treatment (Age 4 weeks to <2 years): 150 IU/kg SC twice daily
- VTE Treatment (Age 2 years to <8 years): 125 IU/kg SC twice daily
- VTE Treatment (Age 8 years to <17 years): 100 IU/kg SC twice daily.
Special Cases:
- Elderly Patients: No specific dose adjustments are typically required, but careful monitoring is recommended.
- Patients with Renal Impairment: Dose reduction may be necessary in severe renal impairment based on anti-Xa levels.
- Patients with Hepatic Dysfunction: Caution is recommended, and monitoring of coagulation parameters is advisable.
- Patients with Comorbid Conditions: Dosage adjustments should be considered based on individual patient risk factors for bleeding.
Clinical Use Cases
- Surgical Procedures: Dalteparin is commonly used for VTE prophylaxis following various surgeries, especially abdominal, orthopedic, and pelvic procedures. Dosing regimens vary depending on the specific surgery and patient risk factors.
- Intubation/Mechanical Ventilation/ICU Use: Dalteparin may be used for VTE prophylaxis in critically ill patients, although specific dosage recommendations should be based on individual patient factors.
Dosage Adjustments
Dose adjustments may be needed for patients with renal impairment, thrombocytopenia, or other bleeding risks. Monitoring of anti-Xa levels may be necessary in some cases.
Side Effects
Common Side Effects
- Bleeding or bruising more easily
- Pain, redness, bruising, or hematoma at the injection site
Rare but Serious Side Effects
- Allergic reactions (e.g., hives, difficulty breathing, swelling of the face)
- Spinal or epidural hematomas (symptoms may include back pain, numbness, muscle weakness)
- Heparin-induced thrombocytopenia (HIT)
Long-Term Effects
Osteoporosis has been reported with long-term use of LMWHs.
Adverse Drug Reactions (ADR)
HIT is a serious ADR that can lead to paradoxical thrombosis. Other ADRs include bleeding complications, allergic reactions, and injection site reactions.
Contraindications
- Hypersensitivity to dalteparin or heparin
- Active major bleeding
- History of heparin-induced thrombocytopenia (HIT)
Drug Interactions
Dalteparin interacts with numerous medications, including other anticoagulants (e.g., warfarin, aspirin, clopidogrel), NSAIDs, and some antibiotics. These interactions can increase the risk of bleeding. Consult a comprehensive drug interaction resource for a complete list.
Pregnancy and Breastfeeding
Dalteparin does not cross the placenta and is considered safe to use during pregnancy. It is also considered safe to use during breastfeeding, as it is minimally excreted in breast milk.
Drug Profile Summary
- Mechanism of Action: Enhances the activity of antithrombin III, inhibiting factors Xa and IIa.
- Side Effects: Bleeding, injection site reactions, HIT (rare).
- Contraindications: Hypersensitivity, active bleeding, HIT history.
- Drug Interactions: Numerous drug interactions, particularly with other anticoagulants and antiplatelets.
- Pregnancy & Breastfeeding: Generally considered safe.
- Dosage: Varies depending on indication and patient characteristics.
- Monitoring Parameters: Platelet count, signs of bleeding, anti-Xa levels (in some cases).
Popular Combinations
Dalteparin is often used in combination with aspirin in the setting of acute coronary syndrome.
Precautions
Careful patient selection is essential, considering risk factors for bleeding. Monitor for signs of bleeding and thrombocytopenia. Epidural or spinal hematomas are a rare but serious complication.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Dalteparin?
A: The dosage depends on the indication and patient factors. See the “Dosage” section above for specific recommendations.
Q2: How is Dalteparin administered?
A: Dalteparin is administered subcutaneously.
Q3: What are the signs of a Dalteparin overdose?
A: Overdose can lead to excessive bleeding.
Q4: Can Dalteparin be used in patients with renal insufficiency?
A: Dose adjustment or close monitoring is required.
Q5: What is Heparin-Induced Thrombocytopenia (HIT)?
A: HIT is a rare but serious complication of heparin therapy characterized by a drop in platelet count and a paradoxical increase in thrombotic risk.
Q6: What are the alternatives to Dalteparin?
A: Other anticoagulants like enoxaparin, fondaparinux, or warfarin may be considered depending on the indication.
Q7: What are the key patient counseling points for Dalteparin?
A: Patients should be educated on how to administer the injection, signs of bleeding to watch for, and the importance of medication adherence.
Q8: How should Dalteparin be stored?
A: Store at room temperature.
Q9: Can Dalteparin be used in children?
A: Yes, dalteparin is used in children for VTE treatment, with dosage adjustments based on age and weight.
Q10: How should bleeding complications due to Dalteparin be managed?
A: Discontinue dalteparin and administer protamine sulfate as an antidote if necessary. Supportive measures may also be required.
