Protamine sulfate

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Protamine sulfate
Clinical data
Trade names Prosulf, others
AHFS/Drugs.com Monograph
Pregnancy
category
  • US: C (Risk not ruled out)
Pharmacokinetic data
Onset of action 5 minutes[1]
Identifiers
CAS Number
DrugBank
ECHA InfoCard 100.113.361

Protamine sulfate is a medication that is used to reverse the effects of heparin.[2] It is specifically used in heparin overdose, in low molecular weight heparin overdose, and to reverse the effects of heparin during delivery.[2] It is given by injection into a vein.[2] The onset of effects is typically within five minutes.[1]

Common side effects include low blood pressure, slow heart rate, allergic reactions, and vomiting.[2] Allergic reactions may be severe and include anaphylaxis.[2] The risk is greater in males who have had a vasectomy.[3] While there is no evidence of harm from using during pregnancy it has not been well studied in this group.[4] Protamine works by binding with heparin.[2]

Protamine sulfate was approved for medical use in the United States in 1969.[2] It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system.[5] The wholesale cost in the developing world is about 2.82 to 12.20 USD per vial.[6] It was originally made from salmon sperm.[2]

Medical uses[edit]

Protamine sulfate is usually administered to reverse the large dose of heparin administered during certain surgeries, especially heart surgery. A dose of protamine is given when the patient is off - pump, when extracorporeal circulation and anticoagulation are no longer needed.

It is also used in gene transfer, protein purification and in tissue cultures as a crosslinker for viral transduction.

In gene therapy, protamine sulfate has been studied as a means to increase transduction rates by both viral[7] and nonviral (e.g. utilizing cationic lipids)[8] mediated delivery mechanisms.

Dosage[edit]

Dosage for heparin reversal is 1.0 -to- 1.5 mg protamine sulfate IV for every 100 IU of active heparin, not to exceed 50 mg. PTT should be monitored at 5–15 minutes after dose then in 2–8 hours afterward.

Adverse effects[edit]

Protamine has been reported to cause allergic reactions in patients who are allergic to fish, diabetics using insulin preparations containing protamine, and vasectomized or infertile men.[9][10] These occur at rates ranging from 0.28% to 6%.[10][11][12]

Avoiding rapid infusion of protamine sulfate and pre-treating at-risk patients with histamine receptor antagonists (H1 and H2) and steroids may minimize these reactions. A 5–10 mg test dose is recommended following pretreatment before administering the full dose.[10]

Mechanism[edit]

It is a highly cationic peptide that binds to either heparin or low molecular weight heparin (LMWH) to form a stable ion pair, which does not have anticoagulant activity. The ionic complex is then removed and broken down by the reticuloendothelial system. In large doses, protamine sulfate may also have an independent—however weak—anticoagulant effect.

History[edit]

Protamine was originally isolated from the sperm of salmon and other species of fish but is now produced primarily through recombinant biotechnology.

References[edit]

  1. ^ a b "Prosulf 10mg/ml Solution for Injection - Summary of Product Characteristics (SPC) - (eMC)". www.medicines.org.uk. Archived from the original on 20 December 2016. Retrieved 14 December 2016. 
  2. ^ a b c d e f g h "Protamine Sulfate". The American Society of Health-System Pharmacists. Archived from the original on 6 November 2016. Retrieved 8 December 2016. 
  3. ^ WHO Model Formulary 2008 (PDF). World Health Organization. 2009. p. 255. ISBN 9789241547659. Archived (PDF) from the original on 13 December 2016. Retrieved 8 December 2016. 
  4. ^ "Protamine Use During Pregnancy | Drugs.com". www.drugs.com. Archived from the original on 21 December 2016. Retrieved 14 December 2016. 
  5. ^ "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. 
  6. ^ "Protamine Sulfate". International Drug Price Indicator Guide. Retrieved 8 December 2016. 
  7. ^ Kenneth Cornetta; W.French Anderson (1989). "Protamine sulfate as an effective alternative to polybrene in retroviral-mediated gene-transfer: implications for human gene therapy". Journal of Virological Methods. 23 (2): 187–194. doi:10.1016/0166-0934(89)90132-8. PMID 2786000. 
  8. ^ Sorgi, FL; Bhattacharya, S; Huang, L (Sep 1997). "Protamine sulfate enhances lipid-mediated gene transfer" (PDF). Gene therapy. 4 (9): 961–8. doi:10.1038/sj.gt.3300484. PMID 9349433. Archived (PDF) from the original on 2014-02-21. 
  9. ^ Walker, WS; Reid, KG; Hider, CF; Davidson, IA; Boulton, FE. (1984). "Successful cardiopulmonary bypass in diabetics with anaphylactoid reactions to protamine". Br Heart J. 52: 112–114. doi:10.1136/hrt.52.1.112. PMC 481594Freely accessible. PMID 6743419. 
  10. ^ a b c Campbell, FW; Goldstein, MF; Atkins, PC. (1984). "Management of the patient with protamine hypersensitivity for cardiac surgery". Anesthesiology. 61: 761–764. doi:10.1097/00000542-198412000-00021. PMID 6334459. 
  11. ^ Welsby, IJ; Newman, MF; Phillips-Bute, B; Messier, RH; Kakkis, ED. (2005). "Hemodynamic changes after protamine administration: association with mortality after coronary artery bypass surgery". Anesthesiology. 102: 308–314. doi:10.1097/00000542-200502000-00011. PMID 15681944. 
  12. ^ Sokolowska, E; Kalaska, B; Miklosz, J; Mogielnicki, A. (2016). "The toxicology of heparin reversal with protamine: past, present and future". Expert Opinion on Drug Metabolism & Toxicology. 6: 1–13. doi:10.1080/17425255.2016.1194395. 

External links[edit]