Enoxaparin sodium

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Enoxaparin sodium
EnoxaparinSodium.png
Enoxaparin sodium ball-and-stick.png
Clinical data
Trade names Lovenox, Clexane, Xaparin, others
AHFS/Drugs.com Monograph
MedlinePlus a696006
License data
Pregnancy
category
  • B
Routes of
administration
subcutaneous (SC), intravenous (IV)
ATC code
Legal status
Legal status
Pharmacokinetic data
Biological half-life 4.5 hours
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
  • none
UNII
KEGG
ChEMBL
Chemical and physical data
Formula (C26H40N2O36S5)n
Molar mass 4500 g/mol (average)
 NYesY (what is this?)  (verify)

Enoxaparin sodium, sold under the brand name Lovenox among others, is an anticoagulant medication (blood thinner).[1] It is used to treat and prevent deep vein thrombosis (DVT) and pulmonary embolism (PE) including during pregnancy and following certain types of surgery.[1] It is also used in those with acute coronary syndrome (ACS) and heart attacks.[1] It is given by injection just under the skin or into a vein.[1] Other uses include inside kidney dialysis machines.[2]

Common side effects include bleeding, fever, and swelling of the legs.[1] Bleeding may be serious especially in those who are undergoing a spinal tap.[1] Use during pregnancy appears to be safe for the baby.[1] Enoxaparin is in the low molecular weight heparin family of medications.[1]

Enoxaparin was first made in 1981 and approved for medical use in 1993.[3][1] It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system.[4] Enoxaparin is available as a generic medication.[1] The wholesale cost in the developing world is about 1.90 to 10.80 USD per day.[5] In the United States the wholesale cost is about 14.13 USD per day as of 2016.[6] Enoxaparin is made from heparin.[3]

Medical uses[edit]

Monitoring[edit]

Enoxaparin has predictable absorption, bioavailability, and distribution therefore monitoring is not typically done. However, there are instances where monitoring may be beneficial for special populations, for example individuals with kidney insufficiency or those that are obese. In this case, anti-Xa units can be measured and dosing adjusted accordingly.[7]

Reversal agent[edit]

Protamine sulfate is less effective at reversing enoxaparin compared to heparin, with a maximum neutralization of approximately 60% of the anti-factor Xa effect.[7]

Pregnancy[edit]

  • Enoxaparin is a FDA pregnancy category B drug which means enoxaparin is not expected to cause harm to an unborn baby when used during pregnancy. This statement is based on reproductive studies involving pregnant rats and rabbits. No birth defects or toxic effects to an unborn fetus due to enoxaparin were observed during these animals studies. However a human's response to enoxaparin might be different than that of a small animal, therefore enoxaparin should be used during pregnancy only if there is a definite need.[7]
  • Enoxaparin does not cross the placenta therefore it is unlikely an unborn baby would be exposed to it.[7]
  • Some fetal deaths have been reported by women who used enoxaparin during pregnancy, but it is unclear if enoxaparin caused these deaths.[7]
  • Pregnant woman on enoxaparin should be monitored on a regular basis for bleeding and/or "excessive anticoagulation" especially when the delivery date is approaching. The risk of hemorrhage is higher during delivery if the person is still using enoxaparin and this could endanger the life of the baby and/or the mom.[7]
  • The multiple-dose vials of the brand name enoxaparin (Lovenox) contain 15 mg benzyl alcohol per 1 mL as a preservative. Premature infants who have been given large amounts of benzyl alcohol (99–405 mg/kg/day) have experienced "gasping syndrome".[7][8]
  • Although enoxaparin is used to prevent blood clots it is necessary to remember that pregnancy alone can raise a woman's risk of clotting.[7]

Side effects[edit]

Uncommon (<1%)

Common (>1%)

  • Thrombocytopenia, i.e. can be associated with heparin-induced thrombocytopenia (0.5-5.0% of persons treated for at least five days)[9]
  • Elevations in serum aminotransferases: 5.9%-6.1%[7]
  • In people undergoing abdominal or colorectal surgery:
  • In persons undergoing hip or knee replacement:
    • Fever, nausea, anemia, edema, peripheral edema: ≥ 2%[7]
  • In persons with severely restricted mobility during acute illness:
    • Dyspnea, thrombocytopenia, confusion, diarrhea, nausea: ≥ 2%[7]
  • In people being treated for deep vein thrombosis:
    • Injection site hemorrhage, injection site pain, hematuria: ≥ 2%[7]

Frequency under investigation

Boxed warning[edit]

The FDA issued a revision to the boxed warning for enoxaparin in October 2013.[10] The revision recommends exercising caution regarding when spinal catheters are placed and removed in persons taking enoxaparin for spinal puncture or neuroaxial anesthesia.[11] It may be necessary to delay anticoagulant dosing in these persons in order to decrease the risk for spinal or epidural hematomas, which can manifest as permanent or long-term paralysis.[11] Persons at risk for hematomas may present with indwelling epidural catheters, concurrent use of medications that worsen bleeding states such as non-steroidal anti-inflammatory drugs (NSAIDs), or a past medical history of epidural or spinal punctures, spinal injury, or spinal deformations.[10] The FDA recommends that at-risk persons be monitored for bleeding and neurological changes.[10][12]

Pharmacology[edit]

Mechanism of action[edit]

Enoxaparin binds to and potentiates antithrombin (a circulating anticoagulant) to form a complex that irreversibly inactivates clotting factor Xa.[13] It has less activity against factor IIa (thrombin) compared to unfractionated heparin (UFH) due to its low molecular weight.[14]

Pharmacokinetics[edit]

Absorption: Bioavailability (subcutaneous injection) ~ 100%[10]

Distribution: Volume of distribution (anti-Factor Xa activity) = 4.3 liters[10]

Metabolism: Enoxaparin is metabolized in the liver into low molecular weight species by either or both desulfation and depolymerization.[10]

Elimination: A single dose of a subcutaneous injection of enoxaparin has an elimination half-life of 4.5 hours.[10] Approximately 10%-40% of the active and inactive fragments from a single dose are excreted by the kidneys.[10] Dose adjustments based on kidney function are necessary in persons with reduced kidney function.[10]

Drug class[edit]

Enoxaparin belongs to the class of drugs known as low molecular weight heparins. Other drugs in this class include dalteparin, fondaparinux and tinzaparin.[15]

References[edit]

  1. ^ a b c d e f g h i j "Enoxaparin Sodium". The American Society of Health-System Pharmacists. Archived from the original on 21 December 2016. Retrieved 8 December 2016. 
  2. ^ "Clexane Forte Syringes - Summary of Product Characteristics (SPC) - (eMC)". www.medicines.org.uk. 6 August 2015. Archived from the original on 20 December 2016. Retrieved 15 December 2016. 
  3. ^ a b Network, Northern Neonatal (2008). Neonatal Formulary: Drug Use in Pregnancy and the First Year of Life. John Wiley & Sons. p. 96. ISBN 9780470750353. Archived from the original on 2016-12-20. 
  4. ^ "WHO Model List of Essential Medicines (19th List)" (PDF). World Health Organization. April 2015. Archived (PDF) from the original on 13 December 2016. Retrieved 8 December 2016. 
  5. ^ "Enoxaparin". International Drug Price Indicator Guide. Retrieved 8 December 2016. 
  6. ^ "NADAC as of 2016-12-07 | Data.Medicaid.gov". Centers for Medicare and Medicaid Services. Archived from the original on 21 December 2016. Retrieved 15 December 2016. 
  7. ^ a b c d e f g h i j k l m n o p q r s "Lovenox® (enoxaparin sodium injection) for subcutaneous and intravenous use Prescribing Information". products.sanofi.us. Archived from the original on 2015-10-23. Retrieved 2015-11-03. 
  8. ^ Gershanik, Juan; Boecler, Betty; Ensley, Harry; McCloskey, Sharon; George, William (1982-11-25). "The Gasping Syndrome and Benzyl Alcohol Poisoning". New England Journal of Medicine. 307 (22): 1384–1388. ISSN 0028-4793. PMID 7133084. doi:10.1056/NEJM198211253072206. 
  9. ^ "Reducing Thrombotic Complications in the Perioperative Setti... : Anesthesia & Analgesia" (PDF). LWW. Retrieved 2015-11-05. 
  10. ^ a b c d e f g h i j "DailyMed - ENOXAPARIN SODIUM- enoxaparin sodium injection". dailymed.nlm.nih.gov. Archived from the original on 2015-10-19. Retrieved 2015-11-05. 
  11. ^ a b Research, Center for Drug Evaluation and. "Drug Safety and Availability - FDA Drug Safety Communication: Updated recommendations to decrease risk of spinal column bleeding and paralysis in patients on low molecular weight heparins". www.fda.gov. Archived from the original on 2015-10-30. Retrieved 2015-11-05. 
  12. ^ Commissioner, Office of the. "Safety Information - Lovenox (enoxaparin sodium) injection". www.fda.gov. Archived from the original on 2016-03-04. Retrieved 2015-11-05. 
  13. ^ Alldredge, Brian; Corelli, Robin; Ernst, Michael; Guglielmo, B. Joseph; Jacobson, Pamela; Kradjan, Wayne; Williams, Bradley. Koda-Kimble and Young's Applied Therapeutics: The Clinical Use of Drugs (Tenth ed.). pp. 347–348. ISBN 1-60913-713-2. 
  14. ^ Trevor, Anthony J., Bertram G. Katzung, and Susan B. Masters. Basic & clinical pharmacology. McGraw-Hill Medical, 2012.
  15. ^ "LowMolecularWeightHeparins". livertox.nih.gov. Archived from the original on 2015-08-28. Retrieved 2015-11-05. 

External links[edit]