Nadroparine

Generic name
Nadroparine
Brand name
ATC Code
B01AB06
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Nadroparine

Dosages
Side effects in children
Warnings & precautions in children
Contra-indications in children

Interactions
PK
Renal impairment
References

Pharmacokinetics in children

Age mean (±SD) Weight (kg) mean (± SD) Cl (L/h/kg)b Vd (L/kg)c T1/2 (h) Reference
Adults       3,5 SmPC Fraxiparine
Child(n=154a) 30 (27) mnd  10 (5,5) 0,037 0,355 6,5 Laporte 1999*
Infants and neonates (n=40) 58,4 (60,4) days; GA 35,2 (4,3) weeks 3,7 (2) 0,068     Chen 2024*

a = All children had underlying congenital heart disease or coronary disease
b = Cl/F
c= Vd/F
* = Data derived from popPK model.
GA= gestational age

dose recommendation of formulary compared to licensed use (on-label versus off-label)

No information is present at this moment.

Available formulations

No information is present at this moment.

Dosages

Prophylaxis for thromboembolic complications
  • Subcutaneous
    • 1 month up to 2 months
      [2] [5] [6] [7]
      • 150 IU/kg/day in 1 dose
        • Titrate the dose based on the concentrations.See warning and precautions section.
    • 2 months up to 2 years
      [2] [5] [7]
      • 120 IU/kg/day in 1 dose
        • Titrate the dose based on the concentrations. See warnings and precautions.
    • 2 years up to 12 years
      [2] [3] [5] [7]
      • 100 IU/kg/day in 1 dose. Max: 2.850 IU/dose. in normal risk. In high risk patients max 5700/IE/dose.
        • Titrate the dose based on the concentrations. See warnings and precautions section.
    • 12 years up to 18 years
      [2] [5] [7]
      • 85.5 IU/kg/day in 1 dose. Max: 2.850 IU/dose. in patients with normal risk. In high-risk patients (including COVID-19 patients) max 5700/dose..
        • Titrate the dose based on the concentrations. See warnings and precautions section.
    • Preterm Term neonate
      [2] [5] [7]
      • 150 IU/kg/day in 1 dose
        • Titrate the dose based on the concentrations.See warning and precautions section.
Treatment thromboembolism
  • Subcutaneous
    • Preterm and Term neonate
      [10] [12] [13]
      • 300 - 360 IU/kg/day in 2 doses.
        • Titrate the dose based on the concentrations. See warnings and precautions section.
    • 1 month up to 2 months
      [1] [3] [4] [5] [6] [7] [9] [11] [12] [13] [14]
      • 300 - 360 IU/kg/day in 2 doses.
        • Titrate the dose based on the concentrations. See warnings and precautions section.
    • 2 months up to 2 years
      [1] [3] [4] [5] [7]
      • 240 IU/kg/day in 2 doses.
        • Titrate the dose based on the concentrations. See warnings and precautions section.
    • 2 years up to 12 years
      [1] [3] [4] [5] [7]
      • 200 IU/kg/day in 2 doses.
        • Titrate the dose based on the concentrations. See warnings and precautions section.
    • 12 years up to 18 years
      [1] [5] [7]
      • 171 IU/kg/day in 2 doses.

      • This corresponds to:

        <40 kg:    85.5 IE/kg BID
        40-49 kg: 7600  IEonce daily or 3800 IE BID
        50-59 kg: 9500 IE once daily or 4750 IE BID
        60-69 kg: 11400 IE once daily or 5700 BID
        70-79 kg: 13300 IE once daily or 6650 IE BID
        80-89 kg: 15200 IE once daily or 7600 BID
        >90 kg:    17100 IE once daily or 8550 IE BID

        • Titrate the dose based on the concentrations. See warnings and precautions section.

Renal impaiment in children > 3 months

Deep venous thrombosis:

  • GFR ≥50: dose adjustment is not necessary.
  • GFR 30-50: 1st dose 100% of normal single dose, then 75% of normal single dose, interval between two doses: 12 hours; if used longer than 3 days, dose according to anti-Xa levels.
  • GFR 10-30: 1st dose 100% of normal single dose, then 50% of normal single dose, interval between doses: 12 hours; if used for more than 3 days, dose according to anti-Xa levels.
  • GFR <10: general advice is not given.

Prophylaxis thromboembolic complications:

  • GFR ≥10: dose adjustment is not required.
  • GFR <10: general advice is not given.
Clinical consequences

With impaired renal function, clearance of low molecular weight heparins may be delayed. This cannot be fully predicted from creatinine clearance.

Clinical effects:
Bleeding.

The complete list of all undesirable drug reactions can be found in the national Summary of Product Characteristics (SmPC) – click here

Side effects

No information is present at this moment.

The complete list of all contra-indications can be found in the national Summary of Product Characteristics (SmPC) – click here

Contra-indications

No information available on specific contra indications in children.

The complete list of all warnings and precautions can be found in the national Summary of Product Characteristics (SmPC) – click here

Warnings & precautions in children

In principle, children under 12 years of age do not receive thrombosis prophylaxis unless they have had a thromboembolism in the past and/or if multiple risk factors for thrombosis are present.

6 mg protaminesulfaat neutralises approximately 950 IE anti-FXa nadroparine.

Anti-FXa levels and monitoring:
Anti-FXa level, measured 4 hours after dose, measure first anti-FXa after 3 doses.
Target anti-FXa level
therapeutic:
in BID dosing LMWH: 0.5 - 1.0 U / mL;
in once daily dosing LMWH: 1.0-2.0 U / mL;
prophylactic: 0.1-0.4 U / mL,
For COVID-19 patients admitted to the ICU: < 0,7 U / mL

> 40 kg: in general no anti-FXa monitoring necessary, except for sick children, co-medication and / or poor kidney function

After possible dose adjustment, it is not necessary to wait for 3 doses. This can be agreed in consultation with the local laboratory. When therapeutic level is reached, further monitoring is only necessary in neonates, severely ill patients, and patients during asparaginase use (due to decreasing antithrombin).

Interactions

The complete list of all interactions can be found in the national Summary of Product Characteristics (SmPC) – click here

ANTITHROMBOTIC AGENTS

This pages provides a list of drugs from the same ATC class for comparison. This does not necessarily mean that these drugs are interchangeable.

Heparin group
B01AB04
B01AB05
B01AB01
Platelet aggregation inhibitors excl. heparin
B01AC06

References

  1. Ommen van CH, et al, Nadroparin Therapy in Pediatric Patients With Venous Thromboembolic Disease, J Pediatr Hematol Oncol, 2008, 30, 230–234
  2. M. Cnossen, Expertopinie sectie Benigne Hematologie profylaxe dosering , 14 jan 2014
  3. CBO, Diagnostiek, preventie en behandeling van veneuze trombo-embolie en secundaire preventie van arteriële trombose, http://www.cbo.nl/thema/Richtlijnen/Overzicht-richtlijnen/, 2009, Geraadpleegd 09jun2010
  4. NVK, Werkboek kinderhematologie, http://www.hematologienederland.nl/werkboek-kinderhematologie, 2014, Geraadpleegd 20-01-14
  5. Klaassen ILM. et al, Are low-molecular-weight heparins safe and effective in children? A systematic review., Blood Rev, 2018, DOI: 10.1016/j.blre.2018.06.003
  6. van Ommen, CH, Expert opinion Behandeling zuigelingen VTE Sectie Kinderhematologie - 29-04-2019
  7. Nederlandse Vereniging voor Kindergeneeskunde, sectie kinderhematologie, Richtlijn Diagnostiek en behandeling van veneuze trombo-embolische complicaties bij neonaten en kinderen tot 18 jaar, https://hematologienederland.nl/kwaliteit/werkboek-kinderhematologie , 2020, jan , 1e revisie
  8. NKFK Workinggroup Acute Kidney Impairment, Extrapolation of KNMP risk analysis "Impaired renal function" for adults to children, 20 Dec 2021
  9. Dutch Pediatric Society, Guideline Neonatal central venous catheter trombosis, https://www.nvk.nl/themas/kwaliteit/richtlijnen/richtlijn?componentid=9207808, 2012
  10. Laporte S, et al , Population pharmacokinetic of nadroparin calcium (Fraxiparine) in children hospitalised for open heart surgery.., Eur J Pharm Sci, 1999, 8(2):, 119-25
  11. Mylan Healthcare B.V, SmPC Fraxiparine (RVG 11878) 15-01-2024, www.geneesmiddelinformatiebank.nl
  12. Chen Y., Is the current therapeutic dosage of nadroparin adequate for neonates and infants under 8 months with thromboembolic disease? a population pharmacokinetic study from a national children's medical center. , Front Pharmacol, 2024, 15, 1331673
  13. Sol J, et al., Effectiveness and Safety of Nadroparin Therapy in Preterm and Term Neonates with Venous Thromboembolism. , J Clin Med, 2021, 10(7)., 1483
  14. Dutch Pediatric Society, Richtlijn Perinatal stroke, https://www.nvk.nl/themas/kwaliteit/richtlijnen/richtlijn?componentid=6881311, 2011

Changes

Therapeutic Drug Monitoring


Overdose