Aprotinin_Dosage, benefits & legal status
Also known as Trasylol, BPTI, bovine pancreatic trypsin inhibitor, Kunitz inhibitor
The clearest case on this site of a regulator reversing itself: suspended on one trial, restored when that trial was re-examined.
Common vial size is what vendors typically sell, not a recommendation. Enter your own vial in the calculator.
What is Aprotinin?
Plain language first. The technical label stays, but it never stands alone.Overview
It stops clots from dissolving, so surgeons used it to reduce blood loss and transfusions in heart surgery. Bayer suspended it worldwide in November 2007 after a trial suggested more deaths, and pulled the remaining stock from hospitals in May 2008. In 2012 European regulators concluded that trial was unreliable and allowed it back for one narrow group of patients, on condition that every center using it joins a registry. The US application is still listed as discontinued, but a synthetic version of the same protein is in a fibrin sealant approved in the United States since 1998.
Aprotinin is a 58-amino-acid protein from bovine lung tissue, a Kunitz-type serine protease inhibitor also called bovine pancreatic trypsin inhibitor. It competitively inhibits trypsin, chymotrypsin, plasmin and kallikrein; inhibiting plasmin slows the breakdown of clots directly, and inhibiting kallikrein blocks formation of factor XIIa.
What it's used for
Reducing blood loss and transfusion in adults at high risk of major bleeding during isolated heart bypass surgery, in Europe. In the United States the injection is discontinued, while synthetic aprotinin is a component of a surgical fibrin sealant.
How does Aprotinin work?
What it does in the body, and where.Clotting and clot-dissolving run against each other all the time. Heart bypass surgery tips the balance toward dissolving, because running blood through a pump activates the enzymes that break clots down. Aprotinin blocks those enzymes.
- 01It blocks plasminPlasmin is the enzyme that chews up fibrin, the mesh a clot is made of. Inhibiting it is the direct route to less bleeding, and it is the same goal as tranexamic acid, the drug that replaced aprotinin in most operating rooms.
- 02It blocks kallikrein as wellKallikrein starts the contact activation pathway, and a pump circuit sets that off. Blocking it reduces that inflammatory and clotting cascade. This broader action is why aprotinin was considered more effective than tranexamic acid, and also why its effects are harder to predict.
- 03Why heparin dosing became a warningAprotinin interferes with the test used to check how thin the blood is during bypass. A reading can look adequate when it is not, so a patient can end up with too little heparin. The US label put minimum targets of 750 seconds on one clotting test and 480 on another while aprotinin was running, and said plainly that it should not be treated as a heparin-sparing agent. Regulators made warning prescribers about this a condition of bringing the drug back, and it is one of the problems they identified in the trial that got it suspended.
A schematic of the compound's mechanism, not a diagnostic image.
What else is it used for?
Each group carries its own evidence level.Approved means regulators have cleared it for that purpose. Investigational means it is in trials. Early research means it is being studied and is not established.
The suspension, and the reversal
Clinical use- Human trialThe BART trial in high-risk heart surgery was stopped early by its own safety monitoring board after preliminary results suggested higher 30-day mortality than with aminocaproic acid or tranexamic acid.
- RegulatoryBayer withdrew the drug worldwide in November 2007 and sales were suspended in May 2008.
- RegulatoryIn February 2012 European regulators concluded those results were unreliable, naming imbalances in heparin use, inappropriate monitoring and the way some patients' data had been excluded, and noted that other studies did not reproduce them.
- RegulatoryThe drug came back in Europe for one narrow group, on condition that centers using it report into a registry. In the United States the application remains listed as discontinued.
Still in use in the US, under another name
FDA-approved- RegulatoryTISSEEL fibrin sealant, approved in the United States since 1998, contains aprotinin at 2250 to 3750 kallikrein inhibitor units per mL as its fibrinolysis inhibitor.
- RegulatoryThat aprotinin is synthetic, made by solid phase synthesis from materials of entirely non-human and non-animal origin. Synthetic manufacture removes the animal-sourcing question, not the allergy risk: the label states that TISSEEL contains aprotinin, a protein known to be associated with anaphylactic reactions, contraindicates it in anyone with known aprotinin hypersensitivity, and warns that people who previously received systemic aprotinin are at higher risk.
- No dataIt is applied to tissue during an operation rather than given into a vein, so the dose that reaches the bloodstream is a different question from the infusion's.
Aprotinin is often described as banned or withdrawn for safety. The accurate version is more interesting: it was suspended in 2008 on one trial's mortality signal, and European regulators then concluded in February 2012 that the trial itself was unreliable and allowed the drug back for one narrow surgical group with a registry attached. Canada had already reinstated it in September 2011. It is also described as unavailable in the United States. That is true of the Trasylol injection and false of the protein: synthetic aprotinin is a labeled component of fibrin sealants approved there, TISSEEL since 1998 and ARTISS since 2008. Synthetic does not mean hypoallergenic, and those labels carry their own anaphylaxis warnings. BPTI, bovine pancreatic trypsin inhibitor and aprotinin are the same protein, and the one in current US products is made synthetically rather than from cattle.
The published record
Papers and trials about Aprotinin
374 papers tagged human · 246 not reviews or lab · 54 clinical trial publications
33 registered trials · 6 with posted results
Furthest stage reached: Approved in the US, no longer sold
Counted from Europe PMC indexing, not read by a person; a human tag can land on reviews, commentary or lab papers; clinical trial publications is the narrower count. 498 papers and 33 trials indexed in detail.
At a glance
Four things to know about Aprotinin
Evidence
FDA-approved
Category
Healing and recovery
Common vial
Varies
Half-life
About 150 minutes, then a 10-hour tail
How much, and do you cycle it?
The range, and whether you take breaks.2 million KIU loading dose, 2 million into the pump, then 500,000 KIU per hour (full-dose regimen), during a single operation. Not applicable Clinical use
It is given during one operation and then stopped. There is no course and no repeat schedule, and repeat exposure raises the risk of an allergic reaction.
About 150 minutes, then a 10-hour tailFDA label
The label gives a plasma half-life of about 150 minutes after the initial distribution phase, and a terminal elimination half-life of about 10 hours beyond five hours. In practice it is loaded and then infused continuously through the operation, so the infusion rate matters more than the half-life.
Source: Trasylol US prescribing information, application 020304
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How is it given?
Dosing context and source notes.Given in hospital from a prepared product, so there is nothing to mix.
The US label gave two regimens, measured in kallikrein inhibitor units. The full dose was 2 million KIU into a vein as a loading dose, 2 million KIU into the pump circuit and 500,000 KIU per hour through the operation; the half-dose regimen was exactly half of each. A 1 mL test dose came at least 10 minutes before the loading dose, because of the anaphylaxis risk. The product was supplied at 10,000 KIU per mL, so the loading dose was 200 mL of liquid. Nothing here is a dose anyone administers outside an operating room.
How do you store it?
Before mixing, and after.Given in a hospital or trial clinic, so the pharmacy stores it.
Aprotinin goes into a vein and is prepared by hospital, clinic or trial pharmacy staff, following the product label or the trial protocol. Some products like this are ready-made solutions and others are powders mixed just before use, often with hours rather than weeks of shelf life once prepared. It is not a medicine people store at home.
What are the side effects and cautions?
Known cautions and warnings for this compound.Solubility, computed: 28% charged residues, 45% hydrophobic. Water usually sufficient.
A first-pass rule from peptide manufacturers' guidance. It does not account for disulfide bridges, salt form or how the powder was dried, and it predicts what should be easy rather than what will happen in your vial.
Who should avoid it
- Any use outside an operating room: this is given by anesthesia and surgical staff during heart surgery
- Heart bypass surgery combined with other cardiovascular procedures: the restored European indication covers isolated bypass surgery only
- Previous exposure to aprotinin within six months, when the labeled reaction rate rises more than fivefold; exposure also counts if it came from a fibrin sealant
- Any product sold as a research peptide under this name: the medicine is a sterile hospital infusion
Stop and get help
- Signs of an allergic or anaphylactic reaction during infusion
- Not applicable outside the operating room, where the surgical team manages it
Common effects
- Managed entirely by the surgical and anesthesia team during the operation
- Allergic reactions, with higher risk on repeat exposure
Where this page says nothing is established, that means nobody has studied it, not that a compound is safe.
Is Aprotinin approved?
And where the numbers on this page come from.Approved, but no longer sold in the United States. Aprotinin was approved by the FDA, and the US product has since been discontinued. It is also approved in the European Union and Canada.
- Approval statusFDA-approved
- RouteInto a vein (loading dose, then infusion during surgery)
- Checked23 October 2026
- Approved outside the USEuropean Union, Canada: Suspended across the EU in 2008, then restored after the CHMP's February 17, 2012 opinion and announced as a European Commission reinstatement on October 10, 2013, limited to adults at high risk of major blood loss undergoing isolated heart bypass surgery and available only through centers that join the aprotinin registry. Canada reinstated its authorization in September 2011. Rights outside the United States were bought from Bayer by Nordic Group in July 2012. The US application is listed as discontinued.This does not change the United States position above.
- DoseFrom the drug label. The manufacturer tested this range and a regulator reviewed it.
- Vial sizeFrom what vendors typically list; not a recommendation.
- SourcesFDA GSRS substance record, aprotinin (UNII 04XPW8C0FL)Drugs@FDA overview for application 020304, TrasylolTrasylol US prescribing information, application 020304EMA recommends lifting the suspension of aprotinin, February 17, 2012Nordic Group announces European Commission reinstatement, October 10, 2013TISSEEL fibrin sealant prescribing information, DailyMed
What has happened recently
A rare case of a suspension being lifted. The US application 020304 for Trasylol, aprotinin 10,000 KIU/mL injection, was approved to Bayer on December 29, 1993 and its marketing status is Discontinued; it is the only product on that application. The FDA issued a statement on the BART trial on October 25, 2007, after BART's safety monitoring board recommended stopping enrollment in the aprotinin arm over a mortality signal. Bayer suspended marketing worldwide in November 2007 pending BART's final results. BART was published in May 2008, and Bayer then told the FDA it would remove all remaining supplies from hospital pharmacies and warehouses, leaving access only through an investigational special treatment protocol. Canada reinstated its authorization in September 2011. On February 17, 2012 the EMA's CHMP concluded that "the results of the BART study on which the suspension was based are unreliable", citing imbalances in heparin use, inappropriate monitoring and how some patient data were excluded, and recommended lifting the suspension for patients undergoing isolated heart bypass surgery at high risk of major blood loss, on condition that an EU registry be set up and prescribers warned about heparin under-dosing. Nordic Group bought the rights from Bayer in July 2012 for all territories except the United States, and announced European Commission reinstatement on October 10, 2013 after a further CHMP opinion in May 2013. Separately, synthetic aprotinin is a labeled component of the fibrin sealants TISSEEL, approved in the United States in 1998, and ARTISS, approved in 2008.
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What else is like Aprotinin?
Others in Healing and recovery, side by side.If you're weighing Aprotinin, it's worth reading Bivalirudin (Angiomax), Calcitonin (salmon), and Canvuparatide in the same class.
The clearest case on this site of a regulator reversing itself: suspended on one trial, restored when that trial was re-examined.
- Dose
- 2 million KIU loading dose, 2 million into the pump, then 500,000 KIU per hour (full-dose regimen)
- How often
- During a single operation
A short-acting synthetic anticoagulant that grips thrombin at two sites. FDA-approved since 2000; it wears off within about an hour.
- Dose
- 0.75 mg/kg bolus, then 1.75 mg/kg/h during the procedure (label)
- How often
- Infusion for the procedure, sometimes up to 4 hours after
A bone hormone borrowed from salmon, and the weakest option in its own category.
- Dose
- Set by the label
- How often
- Daily, by spray or injection
Parathyroid hormone fitted with fatty tails and a self-releasing cap so one injection lasts a week. Phase 3 started in August 2026.
- Dose
- 400 to 1,600 mcg once weekly (phase 3 range; 600 mcg for the first 4 weeks)
- How often
- Once weekly
Guides for this compound
- How to Reconstitute a Peptide
Mix peptide powder with bacteriostatic water, step by step.
- How to Read an Insulin Syringe
Read the units, convert to millilitres, and draw the exact dose.
- mcg vs mg: The Peptide Dosing Mistake to Avoid
Your vial says mg and your protocol says mcg. Here is the conversion and how to check it.
Sources
- FDA GSRS substance record, aprotinin (UNII 04XPW8C0FL)(2026)58 residues, sequence RPDFCLEPPYTGPCKARIIRYFYNAKAGLCQTFVYGGCRAKRNNFKSAEDCMRTCGGA, three disulfide bonds joining residues 5 to 55, 14 to 38 and 30 to 51. CAS 9087-70-1, tagged INN and USAN.
- Drugs@FDA overview for application 020304, Trasylol(2026)Aprotinin 10,000 KIU/mL injection, sponsor Bayer HealthCare, original approval December 29, 1993, marketing status Discontinued. It is the only product on the application, and it is listed as a biologic license application rather than a new drug application.
- Trasylol US prescribing information, application 020304(2006)Describes aprotinin as a natural proteinase inhibitor obtained from bovine lung. Plasma half-life about 150 minutes after distribution, terminal elimination about 10 hours. Full regimen 2 million KIU loading dose, 2 million into the pump prime, 500,000 KIU per hour, after a 1 mL test dose. Anaphylactic reactions 5.0% on re-exposure within six months against 0.9% after longer. States that aprotinin makes the activated clotting time overestimate anticoagulation and should not be viewed as a heparin-sparing agent.
- EMA recommends lifting the suspension of aprotinin, February 17, 2012(2012)Concludes the BART results on which the suspension rested are unreliable, citing heparin imbalances, inappropriate monitoring and excluded patient data, and that other studies did not replicate them. Restores it only for isolated heart bypass surgery in patients at high risk of major blood loss, with an EU registry and a heparin warning as conditions.
- Nordic Group announces European Commission reinstatement, October 10, 2013(2013)States the Commission approved reinstatement following a May 2013 CHMP opinion, for prophylactic use in adults at high risk of major blood loss undergoing isolated cardiopulmonary bypass graft surgery, available only to centers that join the aprotinin registry. Nordic acquired the rights from Bayer in July 2012 for every territory except the United States.
- TISSEEL fibrin sealant prescribing information, DailyMed(2026)Contains synthetic aprotinin at 2250 to 3750 KIU/mL in the reconstituted sealer protein solution, described as a polyvalent protease inhibitor that prevents premature degradation of fibrin, made by solid phase synthesis from materials entirely of non-human and non-animal origin. Baxter Healthcare, initial US approval 1998. The label states that TISSEEL contains aprotinin, a protein known to be associated with anaphylactic reactions, contraindicates known aprotinin hypersensitivity, and flags higher risk in anyone who previously received systemic aprotinin.
Beyond these, 531 records are indexed. Browse the records