Aprotinin
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ammu Susheela, M.D. [2]
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Black Box Warning
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Boxed Warning
See full prescribing information for complete Boxed Warning.
* Trasylol® administration may cause fatal anaphylactic or anaphylactoid reactions. Fatal reactions have occurred with an initial (test) dose as well as with any of the components of the dose regimen.
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Overview
Aprotinin is a protease inhibitor that is FDA approved for the treatment of 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. There is a Black Box Warning for this drug as shown here. Common adverse reactions include anaphylactoid reactions, sepsis, hemoperitoneum, dyspepsia, gastrointestinal hemorrhage, pulmonary hypertension, pulmonary thrombosis, hyperglycemia, arthralgia.
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
- Trasylol® is indicated 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.
Trasylol® given prophylactically in both Regimen A and Regimen B (half Regimen A) to patients undergoing CABG surgery significantly reduced the donor blood transfusion requirement relative to placebo treatment. In low risk patients there is no difference in efficacy between regimen A and B. Therefore, the dosage used (A vs. B) is at the discretion of the practitioner.
- Trasylol® is supplied as a solution containing 10,000 KIU/mL, which is equal to 1.4 mg/mL. All intravenous doses of Trasylol® should be administered through a central line. DO NOT ADMINISTER ANY OTHER DRUG USING THE SAME LINE. Both regimens include a 1 mL initial (test) dose, a loading dose, a dose to be added while recirculating the priming fluid of the cardiopulmonary bypass circuit (“pump prime” dose), and a constant infusion dose. To avoid physical incompatibility of Trasylol® and heparin when adding to the pump prime solution, each agent must be added during recirculation of the pump prime to assure adequate dilution prior to admixture with the other component. Regimens A and B, both incorporating a 1 mL initial (test) dose, are described in the table below:
This image is provided by the National Library of Medicine.
- The 1 ml initial (test) dose should be administered intravenously at least 10 minutes before the loading dose. With the patient in a supine position, the loading dose is given slowly over 20-30 minutes, after induction of anesthesia but prior to sternotomy. In patients with known previous exposure to Trasylol®, the loading dose should be given just prior to cannulation.
- When the loading dose is complete, it is followed by the constant infusion dose, which is continued until surgery is complete and the patient leaves the operating room. The “pump prime” dose is added to the recirculating priming fluid of the cardiopulmonary bypass circuit, by replacement of an aliquot of the priming fluid, prior to the institution of cardiopulmonary bypass. Total doses of more than 7 million KIU have not been studied in controlled trials.
- Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Discard any unused portion.
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Aprotinin in adult patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Aprotinin in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding Aprotinin FDA-Labeled Indications and Dosage (Pediatric) in the drug label.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Aprotinin in pediatric patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Aprotinin in pediatric patients.
Contraindications
Hypersensitivity to aprotinin
- Administration of Trasylol® to patients with a known or suspected previous aprotinin exposure during the last 12 months is contraindicated. For patients with known or suspected history of exposure to aprotinin greater than 12 months previously, see WARNINGS. Aprotinin may also be a component of some fibrin sealant products and the use of these products should be included in the patient history.
Warnings
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Boxed Warning
See full prescribing information for complete Boxed Warning.
* Trasylol® administration may cause fatal anaphylactic or anaphylactoid reactions. Fatal reactions have occurred with an initial (test) dose as well as with any of the components of the dose regimen.
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- Anaphylactic or anaphylactoid reactions have occurred with Trasylol® administration, including fatal reactions in association with the initial (test) dose.
- The initial (test) dose does not fully predict a patient’s risk for a hypersensitivity reaction, including a fatal reaction. Fatal hypersensitivity reactions have occurred among patients who tolerated an initial (test) dose.
- Hypersensitivity reactions often manifest as anaphylactic/anaphylactoid reactions with hypotension the most frequently reported sign of the hypersensitivity reaction. The hypersensitivity reaction can progress to anaphylactic shock with circulatory failure. If a hypersensitivity reaction occurs during injection or infusion of Trasylol®, administration should be stopped immediately and emergency treatment should be initiated.
- Even when a second exposure to aprotinin has been tolerated without symptoms, a subsequent administration may result in severe hypersensitivity/anaphylactic reactions.
- Trasylol® should be administered only in operative settings where cardiopulmonary bypass can be rapidly initiated. Before initiating treatment with Trasylol®, the recommendations below should be followed to manage a potential hypersensitivity or anaphylactic reaction: 1) Have standard emergency treatments for hypersensitivity or anaphylactic reactions readily available in the operating room (e.g., epinephrine, corticosteroids). 2) Administration of the initial (test) dose and loading dose should be done only when the patient is intubated and when conditions for rapid cannulation and initiation of cardiopulmonary bypass are present. 3) Delay the addition of Trasylol® into the pump prime solution until after the loading dose has been safely administered.
- Re-exposure to aprotinin: Administration of aprotinin, especially to patients who have received aprotinin in the past, requires a careful risk/benefit assessment because an allergic reaction may occur. Although the majority of cases of anaphylaxis occur upon re-exposure within the first 12 months, there are also case reports of anaphylaxis occurring upon re-exposure after more than 12 months.
- In a retrospective review of 387 European patient records with documented re-exposure to Trasylol®, the incidence of hypersensitivity/anaphylactic reactions was 2.7%. Two patients who experienced hypersensitivity/anaphylactic reactions subsequently died, 24 hours and 5 days after surgery, respectively. The relationship of these 2 deaths to Trasylol® is unclear. This retrospective review also showed that the incidence of a hypersensitivity or anaphylactic reaction following re-exposure is increased when the re-exposure occurs within 6 months of the initial administration (5.0% for re-exposure within 6 months and 0.9% for re-exposure greater than 6 months). Other smaller studies have shown that in case of re-exposure, the incidence of hypersensitivity/anaphylactic reactions may reach the five percent level.
- An analysis of all spontaneous reports from the Bayer Global database covering a period from 1985 to March 2006 revealed that of 291 possibly associated spontaneous cases of hypersensitivity (fatal: n=52 and non-fatal: n=239), 47% (138/291) of hypersensitivity cases had documented previous exposure to Trasylol®. Of the 138 cases with documented previous exposure, 110 had information on the time of the previous exposure. Ninety-nine of the 110 cases had previous exposure within the prior 12 months.
Renal Dysfunction
- Trasylol® administration increases the risk for renal dysfunction and may increase the need for dialysis in the perioperative period. This risk may be especially increased for patients with pre-existing renal impairment or those who receive aminoglycoside antibiotics or drugs that alter renal function. Data from Bayer’s global pool of placebo-controlled studies in patients undergoing coronary artery bypass graft (CABG) surgery showed that the incidence of serum creatinine elevations >0.5 mg/dL above pre-treatment levels was statistically higher at 9.0% (185/2047) in the high-dose aprotinin (Regimen A) group compared with 6.6% (129/1957) in the placebo group.
- In the majority of instances, post-operative renal dysfunction was not severe and was reversible. However, renal dysfunction may progress to renal failure and the incidence of serum creatinine elevations >2.0 mg/dL above baseline was slightly higher in the high-dose aprotinin group (1.1% vs. 0.8%). Careful consideration of the balance of benefits versus potential risks is advised before administering Trasylol® to patients with impaired renal function (creatinine clearance < 60 mL/min) or those with other risk factors for renal dysfunction (such as perioperative administration of aminogylcoside or products that alter renal function).
Adverse Reactions
Clinical Trials Experience
There is limited information regarding Aprotinin Clinical Trials Experience in the drug label.
Postmarketing Experience
There is limited information regarding Aprotinin Postmarketing Experience in the drug label.
Drug Interactions
There is limited information regarding Aprotinin Drug Interactions in the drug label.
Use in Specific Populations
Pregnancy
Pregnancy Category (FDA):
There is no FDA guidance on usage of Aprotinin in women who are pregnant.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Aprotinin in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of Aprotinin during labor and delivery.
Nursing Mothers
There is no FDA guidance on the use of Aprotinin in women who are nursing.
Pediatric Use
There is no FDA guidance on the use of Aprotinin in pediatric settings.
Geriatic Use
There is no FDA guidance on the use of Aprotinin in geriatric settings.
Gender
There is no FDA guidance on the use of Aprotinin with respect to specific gender populations.
Race
There is no FDA guidance on the use of Aprotinin with respect to specific racial populations.
Renal Impairment
There is no FDA guidance on the use of Aprotinin in patients with renal impairment.
Hepatic Impairment
There is no FDA guidance on the use of Aprotinin in patients with hepatic impairment.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Aprotinin in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Aprotinin in patients who are immunocompromised.
Administration and Monitoring
Administration
There is limited information regarding Aprotinin Administration in the drug label.
Monitoring
There is limited information regarding Aprotinin Monitoring in the drug label.
IV Compatibility
There is limited information regarding the compatibility of Aprotinin and IV administrations.
Overdosage
There is limited information regarding Aprotinin overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.
Pharmacology
There is limited information regarding Aprotinin Pharmacology in the drug label.
Mechanism of Action
There is limited information regarding Aprotinin Mechanism of Action in the drug label.
Structure
There is limited information regarding Aprotinin Structure in the drug label.
Pharmacodynamics
There is limited information regarding Aprotinin Pharmacodynamics in the drug label.
Pharmacokinetics
There is limited information regarding Aprotinin Pharmacokinetics in the drug label.
Nonclinical Toxicology
There is limited information regarding Aprotinin Nonclinical Toxicology in the drug label.
Clinical Studies
There is limited information regarding Aprotinin Clinical Studies in the drug label.
How Supplied
There is limited information regarding Aprotinin How Supplied in the drug label.
Storage
There is limited information regarding Aprotinin Storage in the drug label.
Images
Drug Images
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Package and Label Display Panel
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Patient Counseling Information
There is limited information regarding Aprotinin Patient Counseling Information in the drug label.
Precautions with Alcohol
Alcohol-Aprotinin interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
Brand Names
There is limited information regarding Aprotinin Brand Names in the drug label.
Look-Alike Drug Names
There is limited information regarding Aprotinin Look-Alike Drug Names in the drug label.
Drug Shortage Status
Price
References
The contents of this FDA label are provided by the National Library of Medicine.