Aprotex (Solution, Lyophilisate) Instructions for Use
ATC Code
B02AB01 (Aprotinin)
Active Substance
Aprotinin (Rec.INN registered by WHO)
Clinical-Pharmacological Group
Hemostatic agent. Fibrinolysis inhibitor – polyvalent plasma proteinase inhibitor
Pharmacotherapeutic Group
Proteolysis inhibitor
Pharmacological Action
A polypeptide obtained from bovine lungs. It blocks the kallikrein-kinin system. It inhibits both total proteolytic activity and the activity of individual proteolytic enzymes. It is a polyvalent protease inhibitor (including plasmin, kininogenases, trypsin, chymotrypsin, kallikrein, including those activating fibrinolysis).
It reduces the fibrinolytic activity of blood, inhibits fibrinolysis, and has a hemostatic effect in coagulopathies.
The activity of aprotinin is expressed in kallikrein inactivating units (KIU), in trypsin inactivating units of the European Pharmacopoeia (Ph.Eur.U), and in antitrypsin units (ATrU). 1 Ph.Eur.U corresponds to 1800 KIU. 1 ATrU corresponds to 1.33 KIU.
Pharmacokinetics
Being a polypeptide, aprotinin is inactivated in the gastrointestinal tract. It is excreted in the urine as inactive breakdown products. The terminal half-life (T1/2) is 7-10 hours.
Indications
Pancreatitis (acute, exacerbation of chronic), pancreatic necrosis. Performance of diagnostic studies and operations on the pancreas (prevention of enzymatic autolysis of the pancreas during operations on it and adjacent abdominal organs).
Prevention of acute nonspecific postoperative parotitis.
Bleeding against the background of hyperfibrinolysis: post-traumatic, postoperative (especially during operations on the prostate gland, lungs), before, after and during childbirth (including amniotic fluid embolism); polymenorrhea.
Angioneurotic edema.
Shock (toxic, traumatic, burn, hemorrhagic).
Extensive and deep traumatic tissue damage.
As an adjunct therapy – coagulopathies characterized by secondary hyperfibrinolysis (in the initial phase, before the onset of effect after heparin use and replacement of coagulation factors); massive bleeding (during thrombolytic therapy), during extracorporeal circulation.
Prevention of postoperative pulmonary embolisms and bleeding; fat embolism in polytrauma, especially in fractures of the lower extremities and skull bones.
ICD codes
| ICD-10 code | Indication |
| A48.3 | Toxic shock syndrome |
| D68.8 | Other specified coagulation defects |
| I26 | Pulmonary embolism |
| I74 | Embolism and thrombosis of arteries |
| I82 | Embolism and thrombosis of other veins |
| K11 | Disease of salivary glands |
| K85 | Acute pancreatitis |
| K86.1 | Other chronic pancreatitis |
| N92.0 | Excessive and frequent menstruation with regular cycle (menorrhagia, polymenorrhea) |
| O46 | Antepartum hemorrhage, not elsewhere classified |
| O67.9 | Intrapartum hemorrhage, unspecified |
| O72 | Postpartum hemorrhage |
| R57.1 | Hypovolemic shock |
| R57.8 | Other types of shock |
| R58 | Hemorrhage, not elsewhere classified |
| T14.8 | Other injuries of unspecified body region |
| T78.3 | Angioneurotic edema (Quincke's edema) |
| T79.1 | Fat embolism (traumatic) |
| T79.4 | Traumatic shock |
| T81.0 | Haemorrhage and haematoma complicating a procedure, not elsewhere classified |
| Z03 | Medical observation and evaluation for suspected disease or pathological condition |
| ICD-11 code | Indication |
| 1C45.Z | Toxic shock syndrome without specification of infectious agent |
| 3B4Z | Coagulation disorders, unspecified |
| 3B50.Z | Hereditary disorders of fibrinolysis, unspecified |
| BB00.Z | Thromboembolism in the pulmonary artery system, unspecified |
| BD5Z | Diseases of arteries or arterioles, unspecified |
| BD70.2 | Migratory thrombophlebitis |
| BD7Z | Diseases of veins, unspecified |
| DA04.Z | Diseases of salivary glands, unspecified |
| DB98.5 | Budd-Chiari syndrome |
| DC31.Z | Acute pancreatitis, unspecified |
| DC32.0 | Calcific pancreatitis |
| DC32.1 | Paraduodenal pancreatitis |
| DC32.2 | Hereditary chronic pancreatitis |
| DC32.4 | Chronic idiopathic pancreatitis |
| DC32.5 | Tropical pancreatitis |
| DC32.Z | Chronic pancreatitis, unspecified |
| DC33 | Autoimmune pancreatitis |
| EB04 | Idiopathic angioedema |
| GA20.Z | Menstrual cycle disorders associated with bleeding, unspecified |
| JA41.Z | Antepartum haemorrhage, unspecified |
| JA42.Z | Other intrapartum haemorrhage, unspecified |
| JA43.Z | Postpartum haemorrhage, unspecified |
| MG27 | Hemorrhage, not elsewhere classified |
| MG40.1 | Hypovolemic shock |
| MG40.Z | Shock, unspecified |
| ND56.Z | Unspecified injury of unspecified part of trunk, limb or body region |
| NE81.0Z | Hemorrhage or hematoma of other or unspecified sites complicating a procedure, not elsewhere classified |
| NF0A.1 | Fat embolism (traumatic), not elsewhere classified |
| NF0A.4 | Traumatic shock, not elsewhere classified |
| QA02 | Medical observation or examination for suspected diseases or conditions that were ruled out |
| BD72 | Venous thromboembolism |
| XA60H0 | Vena cava |
Dosage Regimen
| The method of application and dosage regimen for a specific drug depend on its form of release and other factors. The optimal dosage regimen is determined by the doctor. It is necessary to strictly adhere to the compliance of the dosage form of a specific drug with the indications for use and dosage regimen. |
Determine the dosage regimen individually based on the specific indication and clinical situation.
Administer the solution or reconstituted lyophilisate strictly by the intravenous route.
Use either a short-term infusion or a prolonged intravenous infusion as clinically required.
For the initial dose, administer an average of 500,000 KIU intravenously.
Follow the initial dose with a maintenance infusion of 50,000 KIU per hour.
For hyperfibrinolytic bleeding, administer a loading dose of 500,000 KIU followed by 200,000 KIU every 4 hours until bleeding is controlled.
During cardiac surgery with cardiopulmonary bypass, use a high-dose regimen: administer a loading dose of 2,000,000 KIU, add 2,000,000 KIU to the prime volume of the cardiopulmonary bypass circuit, and then infuse 500,000 KIU per hour for the duration of the surgery.
For acute pancreatitis, administer 200,000 to 500,000 KIU daily by slow intravenous infusion.
Adjust the total daily dose and duration of therapy based on the patient’s clinical response and laboratory parameters.
Always administer the initial dose slowly while monitoring the patient closely for signs of anaphylaxis or other hypersensitivity reactions.
Do not exceed the maximum recommended daily dose.
Adverse Reactions
From the cardiovascular system arterial hypotension and/or tachycardia.
Allergic reactions skin rash, urticaria, rhinitis, conjunctivitis, bronchospasm, myalgia, symptoms of anaphylactic reactions up to the development of anaphylactic shock (more often occur after repeated infusions of aprotinin).
From the central nervous system psychotic reactions, hallucinations, confusion.
From the digestive system with rapid administration – nausea, vomiting.
Local reactions with prolonged infusion – thrombophlebitis.
Contraindications
Disseminated intravascular coagulation syndrome (except for the coagulopathy phase), first and third trimesters of pregnancy, lactation period, hypersensitivity to aprotinin, hypersensitivity to bovine protein.
Use in Pregnancy and Lactation
Contraindicated in the first and third trimesters of pregnancy. Clinical data on the safety of aprotinin use in the second trimester of pregnancy and during lactation are lacking.
Use in Renal Impairment
Dosage adjustment is not required for patients with impaired renal function.
Pediatric Use
Use is contraindicated in children and adolescents under 18 years of age.
Geriatric Use
No change in the dosage regimen is required for elderly patients (over 65 years of age).
Special Precautions
Before starting therapy, it is advisable to perform a skin test for individual patient sensitivity to aprotinin. If there is a history of allergic reactions, it is recommended to use histamine H1-receptor blockers and corticosteroids before starting aprotinin therapy.
In hyperfibrinolysis and disseminated intravascular coagulation syndrome, Aprotinin can be used only after all manifestations of disseminated intravascular coagulation syndrome have been eliminated and against the background of the prophylactic action of heparin.
Use with caution in patients who have received muscle relaxants within the previous 2-3 days.
Drug Interactions
Adding aprotinin to heparinized blood causes an increase in whole blood clotting time.
When used concomitantly with rheomacrodex, the sensitizing effect is mutually enhanced.
When used concomitantly, Aprotinin, depending on the dose, inhibits the action of streptokinase, urokinase, and alteplase.
Aprotinin is a weak inhibitor of serum pseudocholinesterase. When used concomitantly, this may contribute to slowing the metabolism of suxamethonium chloride and enhancing muscle relaxation; there is a risk of apnea.
Storage Conditions
Store at 2°C (36°F) to 15°C (59°F). Keep in original packaging, protected from light. Keep out of reach of children.
Dispensing Status
Rx Only
Important Safety Information
This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.
Medical DisclaimerBrand (or Active Substance), Marketing Authorisation Holder, Dosage Form
Lyophilizate for preparation of solution for intravenous administration 100 thousand IU AT: fl. 1, 5, 10, 30, 50, 85 or 100 pcs.
Marketing Authorization Holder
Veropharm, LLC (Russia)
Dosage Form
 |
Aprotex | Lyophilizate for preparation of solution for intravenous administration 100 thousand IU AT: fl. 1, 5, 10, 30, 50, 85 or 100 pcs. |
Dosage Form, Packaging, and Composition
Lyophilizate for preparation of solution for intravenous administration in the form of a white or almost white powder.
| 1 vial | |
| Aprotinin | 100 thousand ATrU |
Excipients : lactose, sodium hydroxide.
100 thousand ATrU – vials (1) – cardboard packs.
100 thousand ATrU – vials (5) – cardboard packs.
100 thousand ATrU – vials (10) – cardboard packs.
100 thousand ATrU – vials (30) – cardboard boxes.
100 thousand ATrU – vials (50) – cardboard boxes.
100 thousand ATrU – vials (85) – cardboard boxes.
100 thousand ATrU – vials (100) – cardboard boxes.
Lyophilizate for the preparation of solution for intravenous administration 10 thousand ATU: fl. 1, 5, 10, 30, 50, 85 or 100 pcs.
Marketing Authorization Holder
Veropharm, LLC (Russia)
Dosage Form
|
Aprotex | Lyophilizate for the preparation of solution for intravenous administration 10 thousand ATU: fl. 1, 5, 10, 30, 50, 85 or 100 pcs. |
Dosage Form, Packaging, and Composition
Lyophilizate for preparation of solution for intravenous administration in the form of a white or almost white powder.
| 1 vial | |
| Aprotinin | 10 thousand ATrU |
Excipients : lactose, sodium hydroxide.
10 thousand ATrU – vials (1) – cardboard packs.
10 thousand ATrU – vials (5) – cardboard packs.
10 thousand ATrU – vials (10) – cardboard packs.
10 thousand ATrU – vials (30) – cardboard boxes.
10 thousand ATrU – vials (50) – cardboard boxes.
10 thousand ATrU – vials (85) – cardboard boxes.
10 thousand ATrU – vials (100) – cardboard boxes.
Solution for infusion 10,000 IU/1 ml: 10 ml bottle 1, 5, 10 or 25 pcs; 50 ml bottle 1 or 5 pcs.
Marketing Authorization Holder
Veropharm, LLC (Russia)
Dosage Form
|
Aprotex | Solution for infusion 10,000 IU/1 ml: 10 ml bottle 1, 5, 10 or 25 pcs; 50 ml bottle 1 or 5 pcs. |
Dosage Form, Packaging, and Composition
| Solution for infusion | 1 ml |
| Aprotinin | 10,000 KIU |
10 ml – bottles (1) – cardboard packs.
10 ml – bottles (5) – cardboard packs with partitions.
10 ml – bottles (10) – cardboard packs with partitions.
10 ml – bottles (25) – cardboard packs with partitions.
50 ml – bottles (1) – cardboard packs.
50 ml – bottles (5) – cardboard packs with partitions.
![Aprotex [Solution, Lyophilisate] 1](https://www.medixlife.com/wp-content/uploads/Medixlife_favi_512.png "Aprotex [Solution, Lyophilisate] 2")