Version July 2025
Acute coronary syndrome (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.
60 to 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: Note: Begin 12 hours after initial bolus. Usual treatment duration: 6 days; plasma anti-Xa levels should be <1.2 anti-Xa units/mL 3 to 4 hours postinjection.
Weight-based dosing: SUBQ: 86 anti-Xa units/kg every 12 hours (maximum total daily dose: 19,000 anti-Xa units/day).
Fixed dosing: SUBQ:
<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.
Deep vein thrombosis, treatment:
Note: For timing of initiating oral anticoagulant, see "Transitioning Between Anticoagulants."
Inpatient treatment:
Patients with standard bleeding risk:
Weight-based dosing: SUBQ: 171 anti-Xa units/kg once daily.
Fixed dosing: SUBQ:
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: Note: For patients with higher-than-average bleeding risk, may administer the same total daily dose in 2 equally divided doses:
Weight-based dosing: SUBQ: 86 anti-Xa units/kg every 12 hours.
Fixed dosing: SUBQ:
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.
Duration of therapeutic anticoagulation (first episode, general recommendations): Optimal duration of therapy is unknown and depends on many factors, such as whether provoking events were present, patient risk factors for recurrence and bleeding, and individual preference.
Provoked deep vein thrombosis: 3 months (provided the provoking risk factor is no longer present) (Ref).
Unprovoked deep vein thrombosis or provoked venous thromboembolism with a persistent risk factor: ≥3 months depending on risk of venous thromboembolism (VTE) recurrence and bleeding (Ref).
Note: All patients receiving indefinite therapeutic anticoagulation with no specified stop date should be reassessed at periodic intervals.
Hemodialysis, intermittent, anticoagulation of circuit: Note: Administer into arterial line at start of each dialysis session; may give additional dose if session lasts longer than 4 hours; adjust dose during subsequent dialysis sessions to plasma anti-Xa levels of 0.5 to 1 anti-Xa units/mL.
Weight-based dosing: Injection into arterial line of hemodialysis circuit: Initial: ~65 anti-Xa units/kg single dose (initial maximum dose: 5,700 anti-Xa units).
Fixed dosing: Injection into arterial line of hemodialysis circuit: 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: Note: Doses may be halved. Administer into arterial line at start of each dialysis session; may give additional smaller dose if session lasts longer than 4 hours; adjust dose during subsequent dialysis sessions to plasma anti-Xa levels of 0.2 to 0.4 anti-Xa units/mL.
Weight-based dosing: Injection into arterial line of hemodialysis circuit: Initial: ~32.5 anti-Xa units/kg single dose (initial maximum dose: 2,850 anti-Xa units).
Fixed dosing: Injection into arterial line of hemodialysis circuit: 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.
Venous thromboembolism, prophylaxis:
General surgery: SUBQ: 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.
Medical patients with acute illness at high risk for venous thromboembolism: Note: Continue for length of hospital stay or until patient is fully ambulatory and risk of VTE has diminished (Ref). Extended prophylaxis beyond acute hospital stay is not routinely recommended (Ref). However, in high-risk COVID-19 patients who are discharged from the hospital, some experts would consider extended prophylaxis with a direct oral anticoagulant (eg, rivaroxaban) (Ref).
≤70 kg: SUBQ: 3,800 anti-Xa units once daily during the risk period of thromboembolism.
>70 kg: SUBQ: 5,700 anti-Xa units once daily during the risk period of thromboembolism.
Hip replacement surgery:
Weight-based dosing: SUBQ: Initial: 38 anti-Xa units/kg (maximum dose: 3,800 anti-Xa units) 12 hours before surgery (if 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 postoperative day 4, begin 57 anti-Xa units/kg once daily (maximum dose: 5,700 anti-Xa units/day).
Fixed dosing: SUBQ:
<50 kg: 1,900 anti-Xa units 12 hours before surgery (if 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 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 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 postoperative day 4, begin 3,800 anti-Xa units once daily.
≥70 kg: 3,800 anti-Xa units 12 hours before surgery (if 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 postoperative day 4, begin 5,700 anti-Xa units once daily.
Duration: Optimal duration of prophylaxis is unknown, but it is usually given for a minimum of 10 to 14 days and can be extended for up to 35 days (Ref); some experts suggest a duration at the higher end of range (eg, 30 days) (Ref).
Transitioning between anticoagulants : Note: This provides general guidance on transitioning between anticoagulants; also refer to local protocol for additional detail:
Transitioning from another anticoagulant to nadroparin:
Transitioning from therapeutic IV unfractionated heparin infusion to therapeutic-dose nadroparin: Discontinue unfractionated heparin (UFH) and begin nadroparin within 1 hour. Note: If aPTT is not in therapeutic range at the time UFH is discontinued, consult local protocol (Ref).
Transitioning from nadroparin to another anticoagulant:
Transitioning from therapeutic-dose nadroparin to therapeutic IV unfractionated heparin infusion: Start IV UFH (rate based on indication) 1 to 2 hours before the next dose of nadroparin would have been due. Note: Omit IV UFH loading dose (Ref).
Transitioning from prophylactic nadroparin to therapeutic IV unfractionated heparin: UFH should be started without delay. A UFH bolus/loading dose may be used if indicated.
Transitioning from therapeutic-dose nadroparin to warfarin: Start warfarin and continue nadroparin until INR is within therapeutic range (Ref). Note: Overlap nadroparin with warfarin until INR is ≥2 for at least 2 measurements taken ~24 hours apart (duration of overlap is ~5 days) (Ref).
Transitioning from therapeutic-dose nadroparin to a direct oral anticoagulant: Start direct oral anticoagulant within 2 hours prior to the next scheduled dose of nadroparin.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
CrCl ≥50 mL/minute: No dosage adjustment necessary.
CrCl ≥30 to <50 mL/minute: Decrease dose by 25% to 33%. Some have suggested that no dose adjustment is needed when used for prophylaxis; one small clinical trial found no change in peak anti-Xa activity after 5 days of nadroparin at prophylactic doses (Ref).
CrCl <30 mL/minute:
Thromboprophylaxis: Reduce dose by 25% to 33%.
Treatment of acute coronary syndromes or deep vein thrombosis: Use is contraindicated.
Hemodialysis: Not dialyzable (Ref).
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Deep vein thrombosis treatment: Some experts do not recommend a fixed upper dose limit (Ref). Consider anti-factor Xa monitoring to ensure a therapeutic dose (Ref).
Thromboprophylaxis: In patients with BMI ≥40 kg/m2, increasing dose by 30% may be appropriate for some indications (Ref).
Refer to adult dosing; use with caution (increased risk of bleeding in older patients). Close monitoring necessary, especially in patients with low body weight (ie, <45 kg) or predisposed to renal impairment.
Thromboprophylaxis in high-risk medical patients (respiratory failure and/or respiratory infection and/or cardiac failure), immobilized due to acute illness or in ICU: Consider dose reduction to 2,850 anti-Xa units once daily during the risk period of thromboembolism.
The following adverse drug reactions are derived from product labeling unless otherwise specified.
Frequency not defined:
Endocrine & metabolic: Calcinosis (injection site), hypoaldosteronism
Genitourinary: Priapism
Hematological & oncologic: Eosinophilia, hemorrhage (including intracranial hemorrhage, major hemorrhage, retroperitoneal hemorrhage), thrombocytopenia
Hepatic: Increased serum alanine aminotransferase, increased serum aspartate aminotransferase
Local: Injection-site reaction (including hematoma at injection site)
Postmarketing:
Dermatologic: Allergic skin reaction (Schultinge 2013), cutaneous calcification (Nuno-Gonzalez 2011, Seront 2016), erythema of skin, pruritus, skin necrosis (Pérez 2016, Malinauskiene 2022), skin rash, urticaria (Chen 2022)
Hematologic & oncologic: Hematoma (Balbay 2004), heparin-induced thrombocytopenia (Malinauskiene 2022, Mumoli 2010)
Hepatic: Hepatic injury (Leo 2019)
Nervous system: Headache, migraine
Hypersensitivity to nadroparin, any component of the formulation, or to other low molecular weight heparins and/or heparin; acute infective endocarditis; active bleeding or increased risk of hemorrhage (hemostasis disorder); history of confirmed or suspected immunologically mediated heparin-induced thrombocytopenia (HIT) (delayed-onset severe thrombocytopenia) or positive in vitro test for antiplatelet antibodies in the presence of nadroparin; major blood clotting disorders; hemorrhagic tendency or other conditions involving increase risk of bleeding; organic lesions likely to bleed (active peptic ulceration); hemorrhagic cerebrovascular event; severe uncontrolled hypertension; diabetic or hemorrhagic retinopathy; injuries to or operations on the CNS, eyes, or ears; severe renal insufficiency (creatinine clearance <30 mL/minute when used for treatment); concomitant use of spinal/epidural anesthesia with repeated high-dose nadroparin (eg, 171 anti-Xa units/kg/day).
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Note: Use of nadroparin in patients with current HIT or HIT with thrombosis is not recommended and considered contraindicated due to high cross-reactivity to heparin-platelet factor-4 antibody (ACCP [Guyatt 2012]; Warkentin 1999).
Concerns related to adverse effects:
• Bleeding: Bleeding may occur at any site during therapy. Monitor patient closely for signs or symptoms of bleeding. Certain patients are at increased risk of bleeding. Risk factors include bacterial endocarditis; congenital or acquired bleeding disorders; active ulcerative or angiodysplastic GI diseases; severe uncontrolled hypertension; hemorrhagic stroke; use shortly after brain, spinal, or ophthalmology surgery; in patients treated concomitantly with other drugs known to cause bleeding (eg, platelet inhibitors); recent GI bleeding or ulceration; vascular disorder of the chorio-retina; thrombocytopenia or platelet defects; severe liver disease; hypertensive or diabetic retinopathy; in patients undergoing invasive procedures; and in older patients. Discontinue if bleeding occurs. Protamine infusion may be necessary for serious bleeding (consult Protamine monograph for dosing recommendations).
• Cutaneous necrosis: Cutaneous necrosis preceded by purpura or infiltrated or painful erythematous blotches has been reported rarely; discontinue treatment immediately if suspected.
• Hyperkalemia: Monitor for hyperkalemia; can cause hyperkalemia possibly by suppressing aldosterone production. Most commonly occurs in patients with risk factors for the development of hyperkalemia (eg, renal dysfunction, concomitant use of potassium-sparing diuretics or potassium supplements, hematoma in body tissues).
• Thrombocytopenia: Cases of thrombocytopenia including thrombocytopenia with thrombosis have occurred. Use with caution in patients with history of thrombocytopenia (drug-induced or congenital) or platelet defects; monitor platelet count closely. Use is contraindicated in patients with a history of confirmed or suspected heparin-induced thrombocytopenia (HIT) or positive in vitro test for antiplatelet antibodies in the presence of nadroparin. Discontinue therapy and consider alternative treatment if platelets are <100,000/mm3 and/or thrombosis develops.
Disease-related concerns:
• Cardiovascular disease: Use with caution in patients with severe arterial hypertension.
• GI disease: Use with caution in patients with history of GI ulceration; contraindicated in patients with active peptic ulceration.
• Hepatic impairment: Use with caution in patients with hepatic impairment (has not been studied); patients with hepatic failure are at an increased risk of bleeding.
• Prosthetic heart valves: Prosthetic valve thrombosis has been reported in patients receiving thromboprophylaxis therapy with low-molecular-weight heparins (LMWHs).
• Renal impairment: Use with caution in patients with renal impairment; primarily renally excreted. Dose reductions may be required. Use is contraindicated in severe renal impairment when treating thromboembolic disorders, unstable angina, and non-ST-elevation myocardial infarction.
Special populations:
• Obesity: There is no consensus for adjusting/correcting the weight-based dosage of LMWH for patients who are morbidly obese (BMI ≥40 kg/m2). The American College of Chest Physicians Practice Guidelines suggest consulting with a pharmacist regarding dosing in bariatric surgery patients and other obese patients who may require higher doses of LMWH (Gould 2012).
• Older patients: Use with caution in older patients; dosage reduction may be needed.
• Elective surgery/procedure: In patients receiving bridging anticoagulation with therapeutic dose nadroparin, the last dose should be administered ~24 hours prior to the surgery/procedure; reinitiate therapy ≥24 hours after the surgery/procedure when bleeding risk is acceptable (ACCP [Douketis 2022]).
Dosage form specific issues:
• Latex: Packaging (needle cover of prefilled syringe) may contain natural latex rubber.
Other warnings/precautions:
• Appropriate use: Do not administer IM.
• Conversion to other products: Not to be used interchangeably (unit for unit) with heparin or any other LMWHs.
• Knee surgery: Risk of bleeding may be increased in patients undergoing knee surgery and receiving LMWHs. Consider risk versus benefit in this population.
• Neuraxial anesthesia: Epidural or spinal hematomas, including subsequent long-term or permanent paralysis, may occur in patients anticoagulated with LMWH or heparinoids who are receiving neuraxial anesthesia (epidural or spinal anesthesia) or undergoing spinal puncture. Consider risk versus benefit prior to spinal procedures; risk is increased by concomitant agents which may alter hemostasis, the use of indwelling epidural catheters, a history of spinal deformity or spinal surgery, or a history of traumatic or repeated epidural or spinal punctures. Avoid lumbar puncture or spinal or epidural anesthesia for 12 hours following the last nadroparin prophylactic dose or 24 hours following the last nadroparin treatment dose. The timing of subsequent nadroparin doses following catheter removal should be based on careful risk assessment for thrombosis and bleeding. Longer intervals should be considered for patients with renal impairment (doubling the timing of catheter removal). Observe patient closely for bleeding and signs and symptoms of neurological impairment if therapy is administered. If spinal hematoma is suspected, diagnose and treat immediately; spinal cord decompression may be considered although it may not prevent or reverse neurological sequelae.
Not available in the US
Yes
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Prefilled Syringe, Injection:
Fraxiparine: 2850 units/0.3 mL (0.3 mL); 3800 units/0.4 mL (0.4 mL); 5700 units/0.6 mL (0.6 mL); 9500 units/mL (1 mL)
Fraxiparine Forte: 11,400 units/0.6 mL (0.6 mL); 15,200 units/0.8 mL (0.8 mL); 19,000 units/mL (1 mL)
SubQ: Administer by SubQ injection into anterolateral abdominal wall with subsequent doses to be administered alternately on right and left side of abdominal wall. The thigh may also be used as an alternative site. Do not administer intramuscularly.
IV: May be administered IV only as initial bolus dose for acute coronary syndromes (unstable angina and NSTEMI [ie, non-Q-wave myocardial infarction]).
Hemodialysis: Inject into arterial line at start of dialysis session.
Note: Not approved in the United States.
Fraxiparine:
Acute coronary syndromes: Treatment of unstable angina and non-ST-elevation myocardial infarction myocardial infarction (MI) (ie, non-Q wave MI).
Deep vein thrombosis: Treatment of deep vein thrombosis (DVT).
Hemodialysis, intermittent, anticoagulation of circuit: Prevention of clotting during hemodialysis.
Venous thromboembolism, prophylaxis: Prophylaxis of thromboembolic disorders (particularly DVT and pulmonary embolism) in general and orthopedic surgery, high-risk medical patients (respiratory failure and/or respiratory infection and/or cardiac failure) immobilized due to acute illness or hospitalized in ICU.
Fraxiparine Forte: Treatment of DVT.
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (anticoagulants, parenteral and oral) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care, Community/Ambulatory Care, and Long-Term Care Settings).
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Acalabrutinib: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor
Aducanumab: May increase anticoagulant effects of Anticoagulants. Management: Avoid use of anticoagulants in patients being treated with aducanumab when possible. If concurrent use is necessary, monitor closely for evidence of intracerebral hemorrhage or other bleeding. Risk D: Consider Therapy Modification
Alemtuzumab: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor
Aliskiren: Heparins (Low Molecular Weight) may increase hyperkalemic effects of Aliskiren. Risk C: Monitor
Alteplase: May increase anticoagulant effects of Anticoagulants. Risk X: Avoid
Anacaulase: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor
Anagrelide: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor
Angiotensin II Receptor Blockers: Heparins (Low Molecular Weight) may increase hyperkalemic effects of Angiotensin II Receptor Blockers. Risk C: Monitor
Angiotensin-Converting Enzyme Inhibitors: Heparins (Low Molecular Weight) may increase hyperkalemic effects of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor
Antidepressants with Antiplatelet Effects: May increase anticoagulant effects of Heparins (Low Molecular Weight). Risk C: Monitor
Antiplatelet Agents (P2Y12 Inhibitors): May increase anticoagulant effects of Heparins (Low Molecular Weight). Risk C: Monitor
Antithrombin: May increase anticoagulant effects of Heparins (Low Molecular Weight). Risk C: Monitor
Apixaban: May increase anticoagulant effects 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. Risk X: Avoid
Aspirin: May increase anticoagulant effects of Heparins (Low Molecular Weight). Risk C: Monitor
Bromperidol: May increase adverse/toxic effects of Anticoagulants. Risk C: Monitor
Caplacizumab: May increase anticoagulant effects of Anticoagulants. Management: Avoid coadministration of caplacizumab with antiplatelets if possible. If coadministration is required, monitor closely for signs and symptoms of bleeding. Interrupt use of caplacizumab if clinically significant bleeding occurs. Risk D: Consider Therapy Modification
Chloroprocaine (Systemic): Anticoagulants may increase adverse/toxic effects of Chloroprocaine (Systemic). Risk C: Monitor
Cilostazol: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor
Collagenase (Systemic): Anticoagulants may increase adverse/toxic effects of Collagenase (Systemic). Specifically, the risk of injection site bruising and/or bleeding may be increased. Risk C: Monitor
Dabigatran Etexilate: May increase anticoagulant effects of Anticoagulants. Refer to separate drug interaction content and to full drug monograph content regarding use of dabigatran etexilate with vitamin K antagonists (eg, warfarin, acenocoumarol) during anticoagulant transition and bridging periods. Risk X: Avoid
Dasatinib: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor
Deferasirox: Anticoagulants may increase adverse/toxic effects of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may be increased. Risk C: Monitor
Defibrotide: May increase anticoagulant effects of Anticoagulants. Risk X: Avoid
Deoxycholic Acid: Anticoagulants may increase adverse/toxic effects of Deoxycholic Acid. Specifically, the risk for bleeding or bruising in the treatment area may be increased. Risk C: Monitor
Desirudin: Anticoagulants may increase anticoagulant effects 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. Risk D: Consider Therapy Modification
Donanemab: May increase anticoagulant effects of Anticoagulants. Management: Avoid use of anticoagulants in patients being treated with donanemab when possible. If concurrent use is necessary, monitor closely for evidence of intracerebral hemorrhage or other bleeding. Risk D: Consider Therapy Modification
Edoxaban: May increase anticoagulant effects of Anticoagulants. Refer to separate drug interaction content and to full drug monograph content regarding 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. Risk X: Avoid
Factor X (Human): Anticoagulants (Inhibitors of Factor Xa) may decrease therapeutic effects of Factor X (Human). Risk C: Monitor
Glycoprotein IIb/IIIa Inhibitors: May increase anticoagulant effects of Heparins (Low Molecular Weight). Risk C: Monitor
Hemin: May increase anticoagulant effects of Anticoagulants. Risk X: Avoid
Herbal Products with Anticoagulant/Antiplatelet Effects: May increase adverse/toxic effects of Anticoagulants. Bleeding may occur. Risk C: Monitor
Ibritumomab Tiuxetan: Anticoagulants may increase adverse/toxic effects of Ibritumomab Tiuxetan. Both agents may contribute to an increased risk of bleeding. Risk C: Monitor
Ibrutinib: Anticoagulants may increase adverse/toxic effects of Ibrutinib. Specifically, the risks of bleeding and hemorrhage may be increased. Risk C: Monitor
Icosapent Ethyl: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor
Inotersen: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor
Kanamycin: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor
Lecanemab: May increase adverse/toxic effects of Anticoagulants. Specifically, the risk of hemorrhage may be increased. Management: Avoid use of lecanemab in patients who are being treated with an anticoagulant when possible. If concurrent use is necessary, monitor closely for evidence of intracerebral hemorrhage or other bleeding. Risk D: Consider Therapy Modification
Limaprost: May increase adverse/toxic effects of Anticoagulants. The risk for bleeding may be increased. Risk C: Monitor
Lipid Emulsion (Fish Oil Based): May increase anticoagulant effects of Anticoagulants. Lipid Emulsion (Fish Oil Based) may decrease anticoagulant effects of Anticoagulants. Risk C: Monitor
Mesoglycan: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor
MiFEPRIStone: May increase adverse/toxic effects of Anticoagulants. Specifically, the risk of bleeding may be increased. Risk X: Avoid
Miscellaneous Antiplatelets: May increase anticoagulant effects of Heparins (Low Molecular Weight). Management: Consider avoiding this combination due to an increased risk of hemorrhage, if possible. If coadministration is required, monitor patients closely for clinical and laboratory evidence of bleeding. Risk D: Consider Therapy Modification
Nintedanib: Anticoagulants may increase adverse/toxic effects of Nintedanib. Specifically, the risk for bleeding may be increased. Risk C: Monitor
Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective): May increase anticoagulant effects of Anticoagulants. Risk C: Monitor
Nonsteroidal Anti-Inflammatory Agents (Nonselective): May increase anticoagulant effects of Nadroparin. Management: Coadministration of NSAIDs and nadroparin is not recommended due to an increased risk of bleeding. If coadministration is required, monitor patients closely for clinical and laboratory signs of bleeding. Risk D: Consider Therapy Modification
Nonsteroidal Anti-Inflammatory Agents (Ophthalmic): May increase anticoagulant effects of Anticoagulants. Risk C: Monitor
Nonsteroidal Anti-Inflammatory Agents (Topical): May increase anticoagulant effects of Anticoagulants. Risk C: Monitor
Obinutuzumab: Anticoagulants may increase adverse/toxic effects of Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased. Management: Consider avoiding coadministration of obinutuzumab and anticoagulants, especially during the first cycle of obinutuzumab therapy. Risk D: Consider Therapy Modification
Omacetaxine: Anticoagulants may increase adverse/toxic effects 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. Risk X: Avoid
Omega-3 Fatty Acids: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor
Ozagrel: May increase anticoagulant effects of Anticoagulants. Management: Avoid coadministration of ozagrel and anticoagulants if possible. If coadministration is required, use caution, monitor patients closely for signs and symptoms of bleeding, and consider ozagrel or anticoagulant dose reductions. Risk D: Consider Therapy Modification
Palifermin: Heparins (Low Molecular Weight) may increase serum concentration of Palifermin. Risk C: Monitor
Pentosan Polysulfate Sodium: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor
Pentoxifylline: May increase anticoagulant effects of Heparins (Low Molecular Weight). Risk C: Monitor
Pirtobrutinib: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor
Potassium Salts: Heparins (Low Molecular Weight) may increase hyperkalemic effects of Potassium Salts. Risk C: Monitor
Potassium-Sparing Diuretics: Heparins (Low Molecular Weight) may increase hyperkalemic effects of Potassium-Sparing Diuretics. Risk C: Monitor
Protein C Concentrate (Human): May increase anticoagulant effects of Anticoagulants. Risk C: Monitor
Reteplase: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor
Rivaroxaban: Anticoagulants may increase anticoagulant effects of Rivaroxaban. Refer to separate drug interaction content and to full drug monograph content regarding use of rivaroxaban with vitamin K antagonists (eg, warfarin, acenocoumarol) during anticoagulant transition and bridging periods. Risk X: Avoid
Salicylates: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor
Streptokinase: May increase anticoagulant effects of Anticoagulants. Risk X: Avoid
Sugammadex: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor
Sulodexide: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor
Tenecteplase: May increase anticoagulant effects of Anticoagulants. Risk X: Avoid
Tibolone: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor
Tipranavir: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor
Urokinase: May increase anticoagulant effects of Anticoagulants. Management: Consider avoiding this combination due to an increased risk of hemorrhage. If anticoagulants are coadministered with urokinase, monitor patients closely for signs and symptoms of bleeding. Risk D: Consider Therapy Modification
Vitamin E (Systemic): May increase anticoagulant effects of Anticoagulants. Risk C: Monitor
Vitamin K Antagonists: Anticoagulants may increase anticoagulant effects of Vitamin K Antagonists. Risk C: Monitor
Volanesorsen: May increase anticoagulant effects of Anticoagulants. Risk C: Monitor
Vorapaxar: May increase adverse/toxic effects of Anticoagulants. More specifically, this combination is expected to increase the risk of bleeding. Risk X: Avoid
Zanubrutinib: May increase adverse/toxic effects of Anticoagulants. Risk C: Monitor
Patients undergoing assisted reproduction therapy (ART) may be at increased risk for thrombosis. Venous thromboembolism prophylaxis is not routinely recommended for patients undergoing ART; however, prophylactic doses of low-molecular-weight heparin (LMWH) are recommended for patients who develop severe ovarian hyperstimulation syndrome (ACCP [Bates 2012]; ASH [Bates 2018]; SOGC [Shmorgun 2017]). In addition, prophylactic doses of LMWH are recommended in patients undergoing ART who have a positive antiphospholipid antibody test but are not diagnosed with antiphospholipid syndrome (APS), as well as patients diagnosed with obstetric APS. Therapeutic doses of LMWH are recommended in patients undergoing ART diagnosed with thrombotic APS (ACR [Sammaritano 2020]).
Low-molecular-weight heparin (LMWH) does not cross the placenta (ACOG 2018).
An increased risk of fetal bleeding or teratogenic effects have not been reported (ACCP [Bates 2012]).
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 (ACOG 2018).
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) (ACCP [Bates 2012]; ACOG 2018; ASH [Bates 2018]; ESC [Regitz-Zagrosek 2018]). LMWH may also be considered for VTE prophylaxis in pregnant patients with COVID-19 (NIH 2023). Consult current recommendations for appropriate use in pregnancy.
LMWH may be used prior to cesarean delivery in patients with additional risk factors for developing VTE. Risk factors may include a personal history of deep vein thrombosis or pulmonary embolism, inherited thrombophilia, or patients with class III obesity (SMFM [Pacheco 2020]).
It is not known if nadroparin is present in breast milk.
Small amounts of another low-molecular-weight heparin (LMWH) have been detected in breast milk; however, because they have a low oral bioavailability, LMWHs are unlikely to cause adverse events in a breastfeeding infant. Breastfeeding is not recommended by the manufacturer; however, LMWH is considered compatible with breastfeeding (ACCP [Bates 2012]; ACOG 2018; ASH [Bates 2018]).
Platelet counts (at baseline and then twice weekly during therapy), bleeding complications including stool occult blood tests, hemoglobin, antifactor Xa levels (recommended to obtain levels 4 hours postdose); renal and hepatic function; potassium in patients at risk for hyperkalemia; signs/symptoms of neurological impairment.
When used for anticoagulation during hemodialysis, carefully monitor patients for signs of bleeding or clotting in the dialysis session.
Anti-Xa level target (measured 4 hours after administration): Treatment of venous thromboembolism (Garcia 2012):
Once-daily dosing: 1.3 Anti-Xa units/mL.
Twice-daily dosing: 0.6 to 1 Anti-Xa units/mL.
Nadroparin is a low molecular weight heparin (LMWH) (average molecular weight is ~4,300 daltons, distributed as 2,000 to 8,000 daltons [75% to 85%]) that binds antithrombin III, enhancing the inhibition of several clotting factors, particularly factor Xa. Nadroparin anti-Xa activity (85 to 110 units/mg) is greater than anti-IIa activity (~27 units/mg) and it has a higher ratio of antifactor Xa to antifactor IIa activity compared to unfractionated heparin. LMWHs have a small effect on the activated partial thromboplastin time.
Note: Values reflective of anti-Xa activity.
Duration: Anti-Xa activity: ≥18 hours
Distribution: Vd: 3.59 L
Metabolism: Hepatic
Bioavailability: SubQ: ~98%
Half-life elimination: ~3.5 hours (prolonged in renal impairment)
Time to peak, serum: SubQ: 3 to 6 hours
Excretion: Urine (primarily)
Altered kidney function: Clearance is decreased. In patients with moderate impairment (CrCl 36 to 43 mL/minute), mean AUC and half-life increased 52% and 39% respectively; in severe impairment (CrCl 10 to 20 mL/minute), mean AUC and half-life increased 95% and 112% respectively. Patients with CrCl <10 mL/minute receiving hemodialysis had mean increases in AUC and half-life of 62% and 65% respectively.
Older adult: Mean anti-Xa peak and total exposure increased 22% and 45% respectively when compared to younger subjects.
