Nadroparin

Nadroparin is an anticoagulant agent belonging to low molecular weight Heparin.

Nadroparin is a low molecular weight heparin used for the prophylaxis of thrombotic events and deep vein thrombosis and prevents unstable angina and non-Q-wave myocardial infarction.

Absorption is linear. The bioavailability of nadroparin after subcutaneous administration is about 89%. The volume of distribution of Nadroparin is 3.59L. Nadroparin is metabolized in the liver. Nadroparin is eliminated via the kidneys through non-saturable mechanisms. In healthy patients, the half-life is between 3.5hrs to 11.2hrs following subcutaneous administration.

Nadroparin shows common side effects like easy bruising, Injection site pain and swelling, Mild irritation, Weakness, Numbness, Dizziness, Headache, Confusion, Fever, Burning, or tingling sensation of the skin.

Nadroparin is available in an Injectable solution.

Nadroparin is available in India, the UK, Canada, China, Malaysia, and Australia.

Nadroparin belonging to the low molecular weight Heparin acts as an anticoagulant agent.

The mechanism of action for nadroparin is similar to all other LMWHs. Like all LMWHs, nadroparin has a Penta saccharide sequence that binds to ATIII, which potentiates the action of ATIII. This complex greatly accelerates the inactivation of factor Xa and factor IIa. As a result, the coagulation cascade is inhibited.

The Data on the onset of action of Nadroparin is not available.

The duration of the Action of Nadroparin is approximately≥18 hours.

The Tmax was found to be approximately 2-6 hours following the administration of Nadroparin.

Nadroparin is available in the form Injectable solution.

Nadroparin injectable solution is given IV (one-time bolus) and subcutaneously (every 12 hours).

Nadroparin is an anticoagulant used to prevent the formation and growth of blood clots in patients with certain specific medical conditions. It is also used to prevent blood clots that may potentially form during certain medical procedures. It is used in combination with aspirin to prevent serious complications associated with angina and heart attacks.

Nadroparin is an anticoagulant agent belonging to low molecular weight Heparin.

Nadroparin has a pentasaccharide sequence that binds to ATIII, which potentiates the action of ATIII. This complex greatly accelerates the inactivation of factor Xa and factor IIa. As a result, the coagulation cascade is inhibited.

Nadroparin is approved for use in the following clinical indications

• Acute coronary syndromes (unstable angina and non–ST-elevation myocardial infarction [non–Q-wave myocardial infarction])

Nadroparin is used to prevent the blockage of coronary arteries (major blood vessels carrying blood and oxygen to the heart) and associated complications. A blockage of the coronary artery may result in a heart attack, anginal pain, and heart rhythm abnormalities. Nadroparin is administered along with aspirin to prevent complications.

• Thromboprophylaxis

Nadroparin is used to prevent the formation of blood clots during major surgical procedures.

● Deep vein thrombosis treatment

Nadroparin is used to treat and prevent the formation of blood clots in veins that could potentially break loose and migrate to larger veins in the legs or lungs, causing further complications.

● Hemodialysis, intermittent, anticoagulation of the circuit

Nadroparin is used for the prevention of clot formation in the extracorporeal circulation during hemodialysis sessions that last more than 1 hour.

• Acute coronary syndromes (unstable angina and non–ST-elevation myocardial infarction [non–Q-wave myocardial infarction])

Initial:

Weight-based dosing

IV: 86 anti-Xa units/kg one-time bolus (maximum dose: 9,500 anti-Xa units).

Fixed dosing: IV:

<50 kg: 3,800 anti-Xa units one-time bolus.

50 to 59 kg: 4,750 anti-Xa units one-time bolus.

60to 69 kg: 5,700 anti-Xa units one-time bolus.

70 to 79 kg: 6,650 anti-Xa units one-time bolus.

80 to 89 kg: 7,600 anti-Xa units one-time bolus.

90 to 99 kg: 8,550 anti-Xa units one-time bolus.

≥100 kg: 9,500 anti-Xa units one-time bolus.

Maintenance:

Weight-based dosing

Subcutaneously: 86 anti-Xa units/kg every 12 hours (maximum total daily dose: 19,000 anti-Xa units/day).

Fixed dosing: Subcutaneously:

<50 kg: 3,800 anti-Xa units every 12 hours.

50 to 59 kg: 4,750 anti-Xa units every 12 hours.

60 to 69 kg: 5,700 anti-Xa units every 12 hours.

70 to 79 kg: 6,650 anti-Xa units every 12 hours.

80 to 89 kg: 7,600 anti-Xa units every 12 hours.

90 to 99 kg: 8,550 anti-Xa units every 12 hours.

≥100 kg: 9,500 anti-Xa units every 12 hours.

• Thromboprophylaxis
  

General surgery:

Subcutaneously: Initial: 2,850 anti-Xa units administered 2 to 4 hours preoperatively; Maintenance: 2,850 anti-Xa units once daily. Continue therapy for at least 7 days and until ambulant or no longer at deep vein thrombosis (DVT) risk.

High-risk medical patients (respiratory failure and/or respiratory infection and/or cardiac failure):

≤70 kg: Subcutaneously: 3,800 anti-Xa units once daily during the risk period of thromboembolism.

>70 kg: Subcutaneously: 5,700 anti-Xa units once daily during the risk period of thromboembolism.

Hip replacement surgery:

Weight-based dosing:

Subcutaneously: Initial: 38 anti-Xa units/kg (maximum dose: 3,800 anti-Xa units) 12 hours before surgery (if the benefit outweighs risks) and again 12 hours after surgery, followed by 38 anti-Xa units/kg once daily (maximum dose: 3,800 anti-Xa units/day) up to and including postoperative day 3; on a postoperative day 4, begin 57 anti-Xa units/kg once daily (maximum dose: 5,700 anti-Xa units/day).

Fixed dosing:

Subcutaneously:

<50 kg: 1,900 anti-Xa units 12 hours before surgery (if the benefit outweighs risks) and again 12 hours after surgery, followed by 1,900 anti-Xa units once daily up to and including postoperative day 3; on a postoperative day 4, begin 2,850 anti-Xa units once daily.

50 to 69 kg: 2,850 anti-Xa units 12 hours before surgery (if the benefit outweighs risks) and again 12 hours after surgery, followed by 2,850 anti-Xa units once daily up to and including postoperative day 3; on a postoperative day 4, begin 3,800 anti-Xa units once daily.

≥70 kg: 3,800 anti-Xa units 12 hours before surgery (if the benefit outweighs risks) and again 12 hours after surgery, followed by 3,800 anti-Xa units once daily up to and including postoperative day 3; on a postoperative day 4, begin 5,700 anti-Xa units once daily.

● Deep vein thrombosis treatment

Patients with standard bleeding risk:

Weight-based dosing:

Subcutaneously: 171 anti-Xa units/kg once daily.

Fixed dosing:

Subcutaneously:

40 to 49 kg: 7,600 anti-Xa units once daily.

50 to 59 kg: 9,500 anti-Xa units once daily.

60 to 69 kg: 11,400 anti-Xa units once daily.

70 to 79 kg: 13,300 anti-Xa units once daily.

80 to 89 kg: 15,200 anti-Xa units once daily.

≥90 kg: 17,100 anti-Xa units once daily.

Patients with increased risk for bleeding:

Weight-based dosing:

Subcutaneously: 86 anti-Xa units/kg every 12 hours.

Fixed dosing:

Subcutaneously:

40 to 49 kg: 3,800 anti-Xa units every 12 hours.

50 to 59 kg: 4,750 anti-Xa units every 12 hours.

60 to 69 kg: 5,700 anti-Xa units every 12 hours.

70 to 79 kg: 6,650 anti-Xa units every 12 hours.

80 to 89 kg: 7,600 anti-Xa units every 12 hours.

≥90 kg: 8,550 anti-Xa units every 12 hours.

● Hemodialysis, intermittent, anticoagulation of the circuit

Weight-based dosing:

Subcutaneously: Initial: ~65 anti-Xa units/kg single dose (initial maximum dose: 5,700 anti-Xa units).

Fixed dosing:

Subcutaneously: Initial:

<50 kg: 2,850 anti-Xa units single dose.

50 to 69 kg: 3,800 anti-Xa units single dose.

≥70 kg: 5,700 anti-Xa units single dose.

• Patients at risk of hemorrhage:

Weight-based dosing:

Subcutaneously: Initial: ~32.5 anti-Xa units/kg single dose (initial maximum dose: 2,850 anti-Xa units).

Fixed dosing:

Subcutaneously: Initial:

<50 kg: 1,425 anti-Xa units single dose.

50 to 69 kg: 1,900 anti-Xa units single dose.

≥70 kg: 2,850 anti-Xa units single dose.

Nadroparin is available in various strengths as 19000 IU/mL solution 1 mL prefilled syringe; 19000 IU/mL solution 0.8 mL prefilled syringe; 9500 IU/mL solution 1 mL prefilled syringe; 9500 IU/mL solution 0.6 mL prefilled syringe; 9500 IU/mL solution 0.4 mL prefilled syringe; 9500 IU/mL solution 0.2 mL prefilled syringe; 19000 IU/ML solution; 9500 IU/ML solution.

Nadroparin is available in the form of an Injectable solution.

Avoid vitamin K-rich foods such as coriander, cabbage, spinach, broccoli, collard greens, kale (leaf cabbage), black licorice, turnip greens, avocados, and Brussels sprouts as they may decrease the effectiveness of Nadroparin. Also, avoid fatty foods and control your cholesterol and triglyceride levels.

Nadroparin is contraindicated in patients with

● Allergy

This medicine is not recommended for use in patients with a known allergy to nadroparin or any other inactive ingredient present along with it. Use of this medicine is also not recommended in patients having a known allergy to heparin or pork products.

● Active major bleeding

This medicine is not recommended for use in patients with known heavy active bleeding due to the increased risk of worsening the patient's condition.

● Thrombocytopenia

This medicine is not recommended for use in patients with an abnormally low platelet count due to the increased risk of excessive bleeding.

● Hemorrhagic cardiovascular events

This medicine is not recommended for use in patients who are at an increased risk of internal bleeding or hemorrhages due to the risk of worsening the patient's condition.

● Regional/local anesthesia

This medicine is not recommended for use in patients with unstable angina, non-Q-wave myocardial infarction, or cancer who are undergoing regional anesthesia due to the increased risk of excessive bleeding.

● Severe kidney damage

This medicine is not recommended for use in patients having severe impairment of kidney function due to the increased risk of worsening the patient's condition.

• Hemorrhage and risk factors

Use of this medicine should be initiated only after internal bleeding or hemorrhage and associated risk factors are ruled out. All the underlying causes of bleeding such as peptic ulcer disease, hemophilia, impaired hemostasis, etc. should also be ruled out before the administration of this medicine

• Thrombocytopenia

The use of this medicine may cause low levels of platelets (thrombocytopenia). It is advised to monitor the blood platelet levels at regular intervals while this medicine is administered. Appropriate dose adjustments or replacement with a suitable alternative may be necessary based on the clinical condition of the patient.

• Benzyl alcohol as a preservative

Dosage forms containing benzyl alcohol as a preservative should not be administered to neonates, infants, or pregnant or breastfeeding women. Benzyl alcohol may cause a fatal adverse event known as the Gasping syndrome in neonates and infants.

• Liver/kidney disease

This medicine should be used with caution in patients having an impairment of normal liver/kidney function. Appropriate dose adjustments and frequent clinical monitoring are recommended for such patients. Replacement with a suitable alternative may be necessary based on the clinical condition.

• Epidural/spinal/regional anesthesia

This medicine should not be used in patients receiving regional, epidural, or spinal anesthesia due to the increased risk of excessive bleeding and the formation of a hematoma.

• Interchangeability with other heparins

This medicine should not be used interchangeably with other low molecular-weight heparins.

Limit alcohol intake since it may cause a rise in blood pressure leading to heart disease.

Nadroparin is not recommended for use in breastfeeding women since its safety and efficacy are not clinically established.

Nadroparin is recommended for use in pregnant women only when absolutely necessary and the potential benefits outweigh the risks involved.

Avoid vitamin K-rich foods such as coriander, cabbage, spinach, broccoli, collard greens, kale (leaf cabbage), black licorice, turnip greens, avocados, and Brussels sprouts as they may decrease the effectiveness of Nadroparin. Also, avoid fatty foods and control your cholesterol and triglyceride levels.

• Common Adverse effects

Arterial thrombosis, thromboembolism, venous thrombosis, skin necrosis, calcinosis, hypoaldosteronism (causing hyperkalemia and/or hyponatremia), Priapism, Eosinophilia, hemorrhage, thrombocythemia, thrombocytopenia, Increased serum alanine aminotransferase, increased serum aspartate aminotransferase, Angioedema, hypersensitivity reaction, nonimmune anaphylaxis, Hematoma at injection site, injection site reaction, Osteopenia.

• Rare Adverse effects

Erythema of skin, headache, migraine, pruritus, skin rash, urticaria.

Nadroparin may interact with the following drugs

● Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): May enhance the anticoagulant effect of Anticoagulants.

● Aliskiren: Heparins (Low Molecular Weight) may enhance the hyperkalemic effect of Aliskiren.

● Angiotensin II Receptor Blockers: Heparins (Low Molecular Weight) may enhance the hyperkalemic effect of Angiotensin II Receptor Blockers.

● Angiotensin-Converting Enzyme Inhibitors: Heparins (Low Molecular Weight) may enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors.

● Antithrombin: May enhance the anticoagulant effect of Heparins (Low Molecular Weight).

● Apixaban: May enhance the anticoagulant effect of Anticoagulants. Refer to separate drug interaction content and to full drug monograph content regarding use of apixaban with vitamin K antagonists (eg, warfarin, acenocoumarol) during anticoagulant transition and bridging periods.

● Collagenase (Systemic): Anticoagulants may enhance the adverse/toxic effect of Collagenase (Systemic). Specifically, the risk of injection site bruising and/or bleeding may be increased.

● Dabigatran Etexilate: May enhance the anticoagulant effect of Anticoagulants. Refer to separate drug interaction content and to full drug monograph content regarding the use of dabigatran etexilate with vitamin K antagonists (eg, warfarin, acenocoumarol) during anticoagulant transition and bridging periods.

● Deferasirox: Anticoagulants may enhance the adverse/toxic effect of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may be increased.

● Deoxycholic Acid: Anticoagulants may enhance the adverse/toxic effect of Deoxycholic Acid. Specifically, the risk for bleeding or bruising in the treatment area may be increased.

● Desirudin: Anticoagulants may enhance the anticoagulant effect of Desirudin. Management: Discontinue treatment with other anticoagulants prior to desirudin initiation. If concomitant use cannot be avoided, monitor patients receiving these combinations closely for clinical and laboratory evidence of excessive anticoagulation.

● Edoxaban: May enhance the anticoagulant effect of Anticoagulants. Refer to separate drug interaction content and to full drug monograph content regarding the use of edoxaban with vitamin K antagonists (eg, warfarin, acenocoumarol) during anticoagulant transition and bridging periods. Management: Some limited combined use may be indicated during periods of transition from one anticoagulant to another. See the full edoxaban drug monograph for specific recommendations on switching anticoagulant treatment.

● Ibritumomab Tiuxetan: Anticoagulants may enhance the adverse/toxic effect of Ibritumomab Tiuxetan. Both agents may contribute to an increased risk of bleeding.

● Mifepristone: May enhance the adverse/toxic effect of Anticoagulants. Specifically, the risk of bleeding may be increased.

● Nintedanib: Anticoagulants may enhance the adverse/toxic effect of Nintedanib. Specifically, the risk of bleeding may be increased.

● Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective): May enhance the anticoagulant effect of Anticoagulants.

● Nonsteroidal Anti-Inflammatory Agents (Topical): May enhance the anticoagulant effect of Anticoagulants.

● Obinutuzumab: Anticoagulants may enhance the adverse/toxic effect of Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased.

● Omacetaxine: Anticoagulants may enhance the adverse/toxic effect of Omacetaxine. Specifically, the risk for bleeding-related events may be increased. Management: Avoid concurrent use of anticoagulants with omacetaxine in patients with a platelet count of less than 50,000/uL.

● Potassium-Sparing Diuretics: Heparins (Low Molecular Weight) may enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Management: Monitor serum potassium concentrations closely. The spironolactone Canadian product monograph lists its combination with heparin or low molecular weight heparins as contraindicated.

● Prostacyclin Analogues: May enhance the adverse/toxic effect of Anticoagulants. Specifically, the antiplatelet effects of these agents may lead to an increased risk of bleeding with the combination.

● Rivaroxaban: Anticoagulants may enhance the anticoagulant effect of Rivaroxaban. Refer to separate drug interaction content and to full drug monograph content regarding the use of rivaroxaban with vitamin K antagonists (eg, warfarin, acenocoumarol) during anticoagulant transition and bridging periods.

● Salicylates: May enhance the anticoagulant effect of Anticoagulants.

● Thrombolytic Agents: May enhance the anticoagulant effect of Anticoagulants. Management: Monitor for signs and symptoms of bleeding if these agents are combined. For the treatment of acute ischemic stroke, avoidance of anticoagulants is often recommended. 

● Vitamin K Antagonists (eg, warfarin): Anticoagulants may enhance the anticoagulant effect of Vitamin K Antagonists.

The common side effect of Nadroparin include the following

Common

• Easy bruising, Injection site pain and swelling, Mild irritation, Weakness, Numbness, Dizziness, Headache, Confusion, Fever, Burning or tingling sensation of the skin.

Rare

• Swelling of eyelids, face, lips, tongue, Difficulty in breathing, Difficulty in swallowing, Back pain, Muscle weakness, Bloody or coffee-colored vomit.

• Pregnancy

Pregnancy category

An increased risk of fetal bleeding or teratogenic effects has not been reported. Due to pregnancy-induced physiologic changes, some pharmacokinetic properties of LMWH may be altered; dosing adjustment may be required. Prophylactic doses of LMWH may also need to be modified in pregnant patients at extremes of body weight. Prosthetic valve thrombosis has been reported in patients receiving thromboprophylaxis therapy with LMWHs; pregnant patients may be at increased risk. The risk of venous thromboembolism (VTE) is increased in pregnant patients, especially during the third trimester and first week postpartum. LMWH is recommended over unfractionated heparin for the treatment of acute VTE in pregnant patients. LMWH is also recommended over unfractionated heparin for VTE prophylaxis in pregnant patients with certain risk factors (eg, homozygous factor V Leiden, antiphospholipid antibody syndrome with ≥3 previous pregnancy losses). Consult current recommendations for appropriate use in pregnancy.

• Nursing Mothers

Nadroparin is not recommended for use in breastfeeding women since its safety and efficacy are not clinically established.

Pharmacodynamic

Nadroparin is a low molecular-weight heparin that is composed of a heterogeneous mixture of sulfated polysaccharide glycosaminoglycan chains. The mean molecular weight is approximately 4300 daltons. The ratio of anti-Xa activity to anti-IIa is 3.5:1 whereas it is about 1:1 for heparin. Its use should be avoided in patients with a creatinine clearance of less than 40mL/min. In these patients, unfractionated heparin should only be used. As for monitoring, active partial thromboplastin time (aPTT) will only increase at high doses of low molecular weight heparins (LMWH). Therefore, monitoring aPTT is not recommended. However, anti-Xa activity can be measured to monitor the efficacy of the LMWH.

Pharmacokinetics

Absorption

Absorption is linear. The bioavailability of nadroparin after subcutaneous administration is about 89%.

• Distribution

The volume of distribution of Nadroparin is 3.59L.

• Metabolism and Excretion

Nadroparin is metabolized in the liver. Nadroparin is eliminated via the kidneys through non-saturable mechanisms. In healthy patients, the half-life is between 3.5hrs to 11.2hrs following subcutaneous administration.

• https://go.drugbank.com/drugs/DB08813
• https://www.uptodate.com/contents/nadroparin-united-states-not-available-drug-information#F198993
• https://www.apollopharmacy.in/salt/NADROPARIN
• https://www.practo.com/medicine-info/nadroparin-775-api
• https://www.medbroadcast.com/drug/getdrug/fraxiparine