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1. Antilysin
2. Basic Pancreatic Trypsin Inhibitor
3. Bovine Kunitz Pancreatic Trypsin Inhibitor
4. Bovine Pancreatic Trypsin Inhibitor
5. Bpti, Basic Pancreatic Trypsin Inhibitor
6. Contrical
7. Contrykal
8. Dilmintal
9. Inactivator, Kallikrein-trypsin
10. Iniprol
11. Kallikrein Trypsin Inactivator
12. Kallikrein-trypsin Inactivator
13. Kontrikal
14. Kontrykal
15. Kunitz Pancreatic Trypsin Inhibitor
16. Pulmin
17. Traskolan
18. Trasylol
19. Trypsin Inhibitor, Basic, Pancreatic
20. Trypsin Inhibitor, Kunitz, Pancreatic
21. Zymofren
1. Iniprol
2. Trazinin
3. Zymofren
4. Trasylol
5. Bpti
6. Riker 52g
7. Bayer A 128
8. Pancreatic Trypsin Inhibitor
9. Rp-9921
10. 9087-70-1
11. Antilysine
12. Aprotinina
13. Aprotinine
14. Aprotininum
15. Antagosan
16. Antikrein
17. Contrykal
18. Inhibin
19. Onquinin
20. Pantinol
21. Protimbin
22. Repulson
23. Trascolan
24. Fosten
25. Gordox
26. Tzalol
27. Kir Richter
28. Trypsin Inhibitor
29. Aprotinin Solution
30. Aprotinin Bovine
31. Basic Protease Inhibitor
32. Aprotinine [inn-french]
33. Aprotininum [inn-latin]
34. Aprotinina [inn-spanish]
35. Unii-04xpw8c0fl
36. 04xpw8c0fl
37. Kallikrein-trypsin Inactivator
38. Kunitz And Northrop Inhibitor
39. Basic Protease Inhibitor (bpi)
40. Baya0128
41. Gtpl6570
42. Hsdb 7502
43. Aprotinin [usan:usp:inn:ban]
44. Basic Pancreatic Trypsin Inhibitor
45. Pancreatic Basic Trypsin Inhibitor
46. Trypsin Inhibitor, Pancreatic Basic
47. Einecs 232-994-9
48. Pancreatic Trypsin Inhibitor (kunitz)
49. Trypsin-kallikrein Inhibitor (kunitz)
50. Rp 9921
51. Rpdfcleppytgpckariiryfynakaglcqtfvyggcrakrnnfksaedcmrtcgga
| Molecular Weight | 6511 g/mol |
|---|---|
| Molecular Formula | C284H432N84O79S7 |
| XLogP3 | -25.4 |
| Hydrogen Bond Donor Count | 93 |
| Hydrogen Bond Acceptor Count | 97 |
| Rotatable Bond Count | 111 |
| Exact Mass | 6510.0514478 g/mol |
| Monoisotopic Mass | 6507.0413833 g/mol |
| Topological Polar Surface Area | 2820 Ų |
| Heavy Atom Count | 454 |
| Formal Charge | 0 |
| Complexity | 16700 |
| Isotope Atom Count | 0 |
| Defined Atom Stereocenter Count | 57 |
| Undefined Atom Stereocenter Count | 0 |
| Defined Bond Stereocenter Count | 0 |
| Undefined Bond Stereocenter Count | 0 |
| Covalently Bonded Unit Count | 1 |
Aprotinin is indicated to reduce perioperative blood loss and the need for blood transfusion in patients undergoing cardiopulmonary bypass in the course of coronary artery bypass graft (CABG) surgery who are at an increased risk for blood loss and blood transfusion. /Included in US product label/
Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2007.
Aprotinin has also been studied for use in the reduction of bleeding and transfusion requirements in other types of surgery including orthotopic liver transplantation, total hip replacement, colorectal surgery, peripheral vascular surgery, and heart and heart-lung transplantation . Study results evaluating the use of aprotinin for these indications are preliminary. Further studies are required to assess aprotinin's efficacy in these indications. /Not included in US product label/
Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2007.
Aprotinin was originally introduced for the treatment of acute pancreatitis because of its proteinase inhibiting property. However, most studies have failed to show any benefit from this use. /Not included in US product label/
Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2007.
The use of aprotinin to control bleeding in emergency cardiac surgery after thrombolysis with alteplase, streptokinase, or urokinase has been reported. Although aprotinin may be effective in preventing severe hemorrhage in this setting, controlled studies to verify its efficacy and safety have not been done. /Not included US product label/
Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2007.
Use of aprotinin for the treatment of subcutaneous insulin resistance syndrome has been described in a limited number of case reports from the early 1980s. /Not included in US product label/
Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2007.
/SIGNS AND SYMPTOMS/ ... Bayer HealthCare Pharmaceuticals Inc. has notified the FDA that the company will begin removing the remaining Trasylol stock from the U.S. market, most of which is in warehouses and hospital or physician's stock. The FDA will work with Bayer to ensure a smooth and complete process. Under a limited use agreement, access to Trasylol is limited to investigational use of the drug according to the procedures described in a special treatment protocol. The protocol allows treatment for certain patients who are at increased risk of blood loss and transfusions during coronary artery bypass graft surgery and who have no acceptable alternative therapy. Physicians using Trasylol in this situation must also verify that the benefits of the drug clearly outweigh the risks for their patients. ... Results from a randomized Canadian study ... suggest that Trasylol appears to increase the risk for death compared to two other antifibrinolytic drugs used in the study.... The FDA has not yet received full study data from the study's researchers at the Ottawa Health Research Institute but supports Bayer's decision to completely remove Trasylol from regular use in the U.S. market. FDA is also reviewing the available Canadian study data to reassess the currently active special treatment protocol that provides access to Trasylol. ...
FDA; FDA News - Manufacturer Removes Remaining Stocks of Trasylol: Access Limited to Investigational Use (May 2008). Available from, as of May 19, 2008: https://www.fda.gov/bbs/topics/NEWS/2008/NEW01834.html
/SIGNS AND SYMPTOMS/ The U.S. Food and Drug Administration (FDA) today /November 5, 2007/ announced that, at the agency's request, Bayer Pharmaceuticals Corp. has agreed to a marketing suspension of Trasylol, a drug used to control bleeding during heart surgery, pending detailed review of preliminary results from a Canadian study that suggested an increased risk for death. FDA requested the suspension in the interest of patient safety based on the serious nature of the outcomes suggested in the preliminary data. FDA has not yet received full study data but expects to act quickly with Bayer, the study's researchers at the Ottawa Health Research Institute, and other regulatory agencies to undertake a thorough analysis of data to better understand the risks and benefits of Trasylol. There are not many treatment options for patients at risk for excessive bleeding during cardiac surgery. Thus, FDA is working with Bayer to phase Trasylol out of the marketplace in a way that does not cause shortages of other drugs used for this purpose. Until FDA can review the data from the terminated study it is not possible to determine and identify a population of patients undergoing cardiac surgery for which the benefits of Trasylol outweigh the risks. Understanding that individual doctors may identify specific cases where benefit outweighs risk, FDA is committed to exploring ways for those doctors to have continued, limited access to Trasylol. ...
FDA; FDA News - FDA Requests Marketing Suspension of Trasylol (November 2007). Available from, as of May 19, 2008: https://www.fda.gov/bbs/topics/NEWS/2007/NEW01738.html
/SIGNS AND SYMPTOMS/ In this multicenter, blinded trial, /the investigators/ randomly assigned 2331 high-risk cardiac surgical patients to one of three groups: 781 received aprotinin, 770 received tranexamic acid, and 780 received aminocaproic acid. The primary outcome was massive postoperative bleeding. Secondary outcomes included death from any cause at 30 days. The trial was terminated early because of a higher rate of death in patients receiving aprotinin. A total of 74 patients (9.5%) in the aprotinin group had massive bleeding, as compared with 93 (12.1%) in the tranexamic acid group and 94 (12.1%) in the aminocaproic acid group (relative risk in the aprotinin group for both comparisons, 0.79; 95% confidence interval [CI], 0.59 to 1.05). At 30 days, the rate of death from any cause was 6.0% in the aprotinin group, as compared with 3.9% in the tranexamic acid group (relative risk, 1.55; 95% CI, 0.99 to 2.42) and 4.0% in the aminocaproic acid group (relative risk, 1.52; 95% CI, 0.98 to 2.36). The relative risk of death in the aprotinin group, as compared with that in both groups receiving lysine analogues, was 1.53 (95% CI, 1.06 to 2.22). Despite the possibility of a modest reduction in the risk of massive bleeding, the strong and consistent negative mortality trend associated with aprotinin, as compared with the lysine analogues, precludes its use in high-risk cardiac surgery.
PMID:18480196 Fergusson DA et al; N Engl J Med.; 358 (22): 2319-31 (2008)
The U.S. Food and Drug Administration (FDA) has approved revised labeling for Trasylol (aprotinin injection) to strengthen its safety warnings and to limit its approved usage to specific situations. Trasylol is given to patients before heart surgery to reduce bleeding and the need for blood transfusions. ... FDA announced on September 29, 2006, that Bayer informed the agency of a safety study on September 27, 2006. The preliminary results from that study suggest that in addition to serious kidney damage, Trasylol may increase the chance for death, congestive heart failure (a weakening of the heart), and strokes. The FDA review of this additional Trasylol safety information is continuing and it may result in other actions, including additional changes to the labeling.
US FDA; FDA News (12/15/2006). Available from, as of March 28, 2007: https://www.fda.gov/bbs/topics/NEWS/2006/NEW01529.html
For more Drug Warnings (Complete) data for APROTININ (29 total), please visit the HSDB record page.
For prophylactic use to reduce perioperative blood loss and the need for blood transfusion in patients undergoing cardiopulmonary bypass in the course of coronary artery bypass graft surgery who are at an increased risk for blood loss and blood transfusion.
FDA Label
Aprotinin is a broad spectrum protease inhibitor which modulates the systemic inflammatory response (SIR) associated with cardiopulmonary bypass (CPB) surgery. SIR results in the interrelated activation of the hemostatic, fibrinolytic, cellular and humoral inflammatory systems. Aprotinin, through its inhibition of multiple mediators [e.g., kallikrein, plasmin] results in the attenuation of inflammatory responses, fibrinolysis, and thrombin generation. Aprotinin inhibits pro-inflammatory cytokine release and maintains glycoprotein homeostasis. In platelets, aprotinin reduces glycoprotein loss (e.g., GpIb, GpIIb/IIIa), while in granulocytes it prevents the expression of pro-inflammatory adhesive glycoproteins (e.g., CD11b). The effects of aprotinin use in CPB involves a reduction in inflammatory response which translates into a decreased need for allogeneic blood transfusions, reduced bleeding, and decreased mediastinal re-exploration for bleeding.
Hemostatics
Agents acting to arrest the flow of blood. Absorbable hemostatics arrest bleeding either by the formation of an artificial clot or by providing a mechanical matrix that facilitates clotting when applied directly to the bleeding surface. These agents function more at the capillary level and are not effective at stemming arterial or venous bleeding under any significant intravascular pressure. (See all compounds classified as Hemostatics.)
Serine Proteinase Inhibitors
Exogenous or endogenous compounds which inhibit SERINE ENDOPEPTIDASES. (See all compounds classified as Serine Proteinase Inhibitors.)
Trypsin Inhibitors
Serine proteinase inhibitors which inhibit trypsin. They may be endogenous or exogenous compounds. (See all compounds classified as Trypsin Inhibitors.)
B - Blood and blood forming organs
B02 - Antihemorrhagics
B02A - Antifibrinolytics
B02AB - Proteinase inhibitors
B02AB01 - Aprotinin
Absorption
100% (IV)
Route of Elimination
Following a single IV dose of radiolabelled aprotinin, approximately 25-40% of the radioactivity is excreted in the urine over 48 hours. After a 30 minute infusion of 1 million KIU, about 2% is excreted as unchanged drug. After a larger dose of 2 million KIU infused over 30 minutes, urinary excretion of unchanged aprotinin accounts for approximately 9% of the dose.
After intravenous (iv) injection, rapid distribution of aprotinin occurs into the total extracellular space, leading to a rapid initial decrease in plasma aprotinin concentration.
Physicians Desk Reference 61st ed, Thomson PDR, Montvale, NJ 2007., p. 754
Following a single iv dose of radiolabelled aprotinin, approximately 25-40% of the radioactivity is excreted in the urine over 48 hours. After a 30 minute infusion of 1 million KIU, about 2% is excreted as unchanged drug. After a larger dose of 2 million KIU infused over 30 minutes, urinary excretion of unchanged aprotinin accounts for approximately 9% of the dose.
Physicians Desk Reference 61st ed, Thomson PDR, Montvale, NJ 2007., p. 754
Animal studies have shown that aprotinin is accumulated primarily in the kidney. Aprotinin, after being filtered by the glomeruli, is actively reabsorbed by the proximal tubules in which it is stored in phagolysosomes.
Physicians Desk Reference 61st ed, Thomson PDR, Montvale, NJ 2007., p. 754
There are no available studies on the distribution of aprotinin into breast milk.
Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2007.
For more Absorption, Distribution and Excretion (Complete) data for APROTININ (9 total), please visit the HSDB record page.
Aprotinin is slowly degraded by lysosomal enzymes.
Aprotinin is slowly degraded by lysosomal enzymes. The physiological renal handling of aprotinin is similar to that of other small proteins, e.g., insulin.
Physicians Desk Reference 61st ed, Thomson PDR, Montvale, NJ 2007., p. 754
Following this distribution phase, a plasma half-life of about 150 minutes is observed. At later time points, (i.e., beyond 5 hours after dosing) there is a terminal elimination phase with a half-life of about 10 hours.
Following this distribution phase, a plasma half-life of about 150 minutes is observed. At later time points, (i.e., beyond 5 hours after dosing) there is a terminal elimination phase with a half-life of about 10 hours.
Physicians Desk Reference 61st ed, Thomson PDR, Montvale, NJ 2007., p. 754
Aprotinin inhibits serine proteases including trypsin, chymotrypsin and plasmin at a concentration of about 125,000 IU/mL, and kallikrein at 300,000 IU/mL. The inhibition of kallikrein inhibits formation of factor XIIa. This inhibits the intrinsic pathway of coagulation and fibrinolysis. Inhibition of plasmin also slows fibrinolysis.
Aprotinin is a broad spectrum protease inhibitor which modulates the systemic inflammatory response (SIR) associated with cardiopulmonary bypass (CPB) surgery. SIR results in the interrelated activation of the hemostatic, fibrinolytic, cellular and humoral inflammatory systems. Aprotinin, through its inhibition of multiple mediators (e.g., kallikrein, plasmin) results in the attenuation of inflammatory responses, fibrinolysis, and thrombin generation.
Physicians Desk Reference 61st ed, Thomson PDR, Montvale, NJ 2007., p. 754
Aprotinin inhibits pro-inflammatory cytokine release and maintains glycoprotein homeostasis. In platelets, aprotinin reduces glycoprotein loss (e.g., GpIb, GpIIb/IIIa), while in granulocytes it prevents the expression of pro-inflammatory adhesive glycoproteins (e.g., CD11b).
Physicians Desk Reference 61st ed, Thomson PDR, Montvale, NJ 2007., p. 754
The effects of aprotinin use in ... /cardiopulmonary bypass/ involves a reduction in inflammatory response which translates into a decreased need for allogeneic blood transfusions, reduced bleeding, and decreased mediastinal re-exploration for bleeding.
Physicians Desk Reference 61st ed, Thomson PDR, Montvale, NJ 2007., p. 754
Aprotinin is thought to improve hemostasis during and after cardiopulmonary bypass by preserving platelet membrane receptors that maintain the adhesive and aggregative capacity of platelets. In addition, aprotinin inhibits fibrinolysis through inhibition of plasmin and plasma and tissue kallikreins. Because of its effects on kallikrein, aprotinin also inhibits activation of the intrinsic clotting system (i.e., contact phase of coagulation), a process that both initiates coagulation and promotes fibrinolysis. The relative contribution of these effects of aprotinin to the drug's therapeutic action remains to be fully elucidated.
McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2007., p. 1574
For more Mechanism of Action (Complete) data for APROTININ (6 total), please visit the HSDB record page.
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