Nadroparin

Usage

Nadroparin is prescribed for the prophylaxis and treatment of venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE). It is also used for the prevention of clotting during hemodialysis and in combination with aspirin for the management of unstable angina and non-Q wave myocardial infarction. It is classified as an anticoagulant, specifically a low molecular weight heparin (LMWH). Nadroparin works by binding to antithrombin III, which in turn inhibits factor Xa and thrombin, key components in the coagulation cascade. This prevents the formation and extension of blood clots.

Alternate Names

Nadroparin Calcium is the chemical name. Fraxiparine and Fraxodi are common brand names.

How It Works

Pharmacodynamics: Nadroparin primarily exerts its anticoagulant effect by accelerating the inhibition of factor Xa by antithrombin III. It has a weaker effect on thrombin inhibition compared to unfractionated heparin. This preferential inhibition of factor Xa contributes to its predictable anticoagulant response.

Pharmacokinetics:

• Absorption: Nadroparin is administered subcutaneously (SC) or intravenously (IV). SC administration results in approximately 89% bioavailability. Absorption is linear.
• Distribution: Nadroparin has a lower protein binding affinity compared to unfractionated heparin.
• Metabolism: It is metabolized in the liver.
• Elimination: Primarily eliminated through renal excretion by non-saturable mechanisms. The half-life after SC administration ranges from 3.5 to 11.2 hours in healthy individuals.

Mode of Action: Nadroparin binds to antithrombin III, a natural anticoagulant. This binding enhances antithrombin III’s ability to neutralize factor Xa, a crucial enzyme in the coagulation cascade. By inhibiting factor Xa, nadroparin disrupts the formation of thrombin, another key enzyme responsible for converting fibrinogen to fibrin, the building blocks of blood clots. This ultimately prevents clot formation and extension.

Dosage

Standard Dosage

Adults:

• VTE Prophylaxis (General Surgery): 2850 anti-Xa IU SC once daily, starting 2-4 hours before surgery, for at least 7 days or until ambulatory.
• VTE Prophylaxis (Orthopedic Surgery): Initial doses of 38 anti-Xa IU/kg SC 12 hours before and 12 hours after surgery, followed by once daily dosing. Increase the dose by 50% or up to 57 anti-Xa IU/kg starting on day 4 post-op, continuing for at least 10 days or until ambulatory.
• VTE Treatment: 86 anti-Xa IU/kg SC every 12 hours or 171 anti-Xa IU/kg SC once daily for about 10 days.
• Unstable Angina/Non-Q Wave MI: 86 anti-Xa IU/kg IV bolus followed by SC injection every 12 hours, in conjunction with aspirin (75-325 mg daily after a loading dose). Treatment typically lasts for 6 days.
• Hemodialysis: For sessions <4 hours: <50 kg: 2850 anti-Xa IU; 50-69 kg: 3800 anti-Xa IU; ≥70 kg: 5700 anti-Xa IU into the arterial line at the start of dialysis. An additional dose may be given for sessions >4 hours.

Children:

Nadroparin is not recommended for children and adolescents due to insufficient safety and efficacy data.

Special Cases:

• Elderly Patients: Dose reduction may be considered for high-risk medical patients (e.g., respiratory or cardiac failure) who are immobilized or in the ICU. Renal function should be assessed before initiating therapy.
• Patients with Renal Impairment: Dose reduction (25-33%) is recommended for creatinine clearance (CrCl) 30-50 mL/min. Contraindicated for CrCl <30 mL/min when used for the treatment of thromboembolic disorders, unstable angina, or non-Q wave MI. Dose reduction may be needed for prophylaxis with CrCl <50 mL/min.
• Patients with Hepatic Dysfunction: Exercise caution, as there is an increased risk of bleeding.
• Patients with Comorbid Conditions: Consider dose adjustments and close monitoring for patients with conditions such as hypertension, history of peptic ulcer disease, or other bleeding risks.

Clinical Use Cases

• Intubation: Prophylactic dosing based on the surgical/medical indication.
• Surgical Procedures: Dosing as per guidelines for VTE prophylaxis in general or orthopedic surgery.
• Mechanical Ventilation: Prophylactic dosing as per the medical indication, considering the increased risk of VTE.
• Intensive Care Unit (ICU) Use: Prophylactic dosing for high-risk medical patients. Dose reduction may be appropriate for certain patients.
• Emergency Situations: Nadroparin is not typically used in emergency situations like cardiac arrest. For acute VTE in emergency settings, consider other LMWHs or unfractionated heparin.

Dosage Adjustments

Dose adjustments are necessary based on renal function, body weight, and bleeding risk. Therapeutic drug monitoring using anti-Xa levels is not routinely recommended but may be considered in certain situations.

Side Effects

Common Side Effects:

• Bleeding (e.g., bruising, nosebleeds, gum bleeding)
• Injection site reactions (pain, redness, swelling)
• Mild irritation

Rare but Serious Side Effects:

• Heparin-induced thrombocytopenia (HIT)
• Severe bleeding (e.g., gastrointestinal, intracranial)
• Allergic reactions (rash, urticaria, anaphylaxis)
• Spinal or epidural hematoma (with neuraxial anesthesia)

Long-Term Effects:

• Osteoporosis (with prolonged use)

Adverse Drug Reactions (ADR):

• HIT, severe bleeding, allergic reactions

Contraindications

• Hypersensitivity to nadroparin, heparin, or LMWHs
• History of HIT with nadroparin
• Active bleeding or increased risk of hemorrhage (except DIC not induced by heparin)
• Severe renal impairment (CrCl < 30 mL/min) for treatment indications
• Acute infectious endocarditis
• Lesions likely to bleed

Drug Interactions

Nadroparin’s effects may be potentiated by other anticoagulants (e.g., warfarin, aspirin, clopidogrel), corticosteroids, and dextrans. Caution is advised when using nadroparin with these medications. Concomitant use with ACE inhibitors or potassium-sparing diuretics may increase the risk of hyperkalemia.

Pregnancy and Breastfeeding

Nadroparin is categorized as Pregnancy Category C. Animal studies have not shown teratogenic effects, but human data is limited. Use only if the benefits outweigh the risks. Nadroparin is excreted in breast milk in small amounts; however, due to its high molecular weight and poor oral absorption, significant adverse effects on the infant are unlikely. Use with caution during breastfeeding.

Drug Profile Summary

• Mechanism of Action: Accelerates factor Xa inhibition by antithrombin III.
• Side Effects: Bleeding, injection site reactions, HIT (rare), allergic reactions (rare).
• Contraindications: Hypersensitivity, HIT history, active bleeding, severe renal impairment (for treatment).
• Drug Interactions: Other anticoagulants, corticosteroids, dextrans.
• Pregnancy & Breastfeeding: Category C; use with caution.
• Dosage: Variable based on indication and patient factors.
• Monitoring Parameters: Platelet count, signs of bleeding, hemoglobin.

Popular Combinations

Nadroparin is often used in combination with aspirin for unstable angina and non-Q wave myocardial infarction.

Precautions

Standard precautions apply regarding pre-existing medical conditions and concomitant medications. Renal function should be assessed, especially in the elderly. Close monitoring for signs of bleeding is crucial. Platelet counts should be monitored regularly due to the risk of HIT. For pregnant or breastfeeding women, careful risk-benefit assessment is necessary.

FAQs

Q1: What is the recommended dosage for Nadroparin?

A: Dosage varies depending on the indication (prophylaxis or treatment), patient weight, and renal function. See the detailed dosage section above.

Q2: How is Nadroparin administered?

A: Nadroparin is administered subcutaneously (SC) for most indications. In cases of unstable angina or NSTEMI, an initial intravenous (IV) bolus is followed by SC injections. For hemodialysis, it’s administered into the arterial line. It’s important not to administer it intramuscularly (IM).

Q3: What are the major side effects of Nadroparin?

A: The most significant side effect is bleeding. Patients should be monitored closely for any signs of bleeding or bruising. Heparin-induced thrombocytopenia (HIT), though rare, is another serious adverse reaction.

Q4: Can Nadroparin be used during pregnancy?

A: Nadroparin is a Pregnancy Category C drug. It should only be used if the potential benefits outweigh the potential risks to the fetus. Consult with specialists and consider the individual patient’s risk factors for VTE.

Q5: What are the contraindications to using Nadroparin?

A: Contraindications include hypersensitivity to nadroparin or other heparins, history of HIT with nadroparin, active major bleeding, severe renal impairment (for therapeutic indications), and acute infectious endocarditis.

Q6: How does Nadroparin interact with other medications?

A: Nadroparin can interact with other anticoagulants (e.g., warfarin, aspirin), increasing the risk of bleeding. It can also interact with certain medications like ACE inhibitors, potentially leading to hyperkalemia. A thorough medication review is essential before starting nadroparin.

Q7: How should I monitor a patient receiving Nadroparin?

A: Regular monitoring of complete blood count (CBC), especially platelet count, is crucial to detect thrombocytopenia. Observe for any signs of bleeding (e.g., bruising, bleeding gums, blood in urine or stool). Monitor renal function, especially in elderly patients and those with pre-existing renal impairment.

Q8: What should I do in case of a Nadroparin overdose?

A: The primary sign of overdose is hemorrhage. If bleeding is minor, withholding subsequent doses and observation might suffice. In cases of significant bleeding, administration of protamine sulfate can partially reverse the anticoagulant effect of nadroparin.

Q9: Is Nadroparin safe for use in patients with hepatic impairment?

A: Use with caution in patients with hepatic impairment, as they may have an increased risk of bleeding. Close monitoring is essential. Dose adjustments may be needed based on the severity of liver dysfunction.