Aprotex - instructions for use, dose, side effects, contraindications

Multivalent inhibitor protease, has anti-proteolytic, antifibrinolytic, hemostatic action. Inactivates plasma proteinases (plasmin, trypsin, chymotrypsin, kallikrein, incl. activating fibrinolysis), blood cells and tissues, which play an important role in pathophysiological processes. The therapeutic effect of aprotinin is primarily due to the suppression of the proteolytic action of plasmin and activation blockade plasminogen by autogenous activators. The presence of antiprotease activity determines the effectiveness of pancreatic and other conditions accompanied by a high content of kallikrein and other proteinases in plasma and tissues. Reduces the fibrinolytic activity of the blood, inhibits fibrinolysis and exerts a haemostatic effect with coagulopathy. Blockade of kallikrein-kinin system allows to use aprotinin for the prevention and treatment of various forms shock, with angioneurotic edema.

Pharmacokinetics:

After intravenous administration it is quickly distributed in the extracellular space, briefly accumulated in the liver. It is inactivated in the gastrointestinal tract, part is destroyed in the liver. The half-life (T1 / 2) of plasma is about 150 min. Terminal T1 / 2 - 7-10 hours.Slowly destroyed by the action of lysosomal enzymes of the kidneys to inactive products and is excreted for 5-6 hours.

Indications:

Pancreatitis (acute, exacerbation of chronic), pancreonecrosis, prevention postoperative pancreatitis.

Hyperfibrinolytic bleeding:

- Post traumatic;

- Postoperative (including, associated with operations on the prostate gland, lungs);

- bleeding before, during and after childbirth (including embolism with amniotic fluid), polymenorrhea;

- complications of thrombolytic therapy;

Prevention of bleeding during open surgery heart with the use of apparatus of artificial circulation;

Treatment and prevention of various forms of shock (endotoxic, traumatic, hemolytic);

Coagulopathies characterizing secondary hyperfibrinolysis;

Prevention of embolism (postoperative, with polytrauma);

Prevention of postoperative mumps.

Contraindications:Hypersensitivity to aprotinin, other components of the drug, the protein of cattle; syndrome of disseminated intravascular coagulation (DVS-syndrome) (with the exception of the coagulopathy phase); pregnancy (I and III trimesters); lactation period.

Carefully:Cardiopulmonary shunting operations, deep hypothermia, allergic reactions in the anamnesis, previous treatment with aprotinin, stopping blood circulation during surgery with the use of the cardiopulmonary bypass (the risk of developing kidney failure and death), and patients who received muscle relaxants 2-3 days before .

Pregnancy and lactation:

It is possible to use in the second trimester of pregnancy only for life indications.

The clinical experience of using aprotinin during lactation is not enough. When the need to prescribe the drug, breastfeeding should be discontinued (at the time of application).

Dosing and Administration:

Intravenously.

Aprotinin is administered only in the "lying" position, intravenously struino slowly (maximum - 5 ml per minute) or drip.

Typically, the following dosage regimens are prescribed:

With bleeding and hemorrhage associated with hyperfibrinolysis, in / in the drip - 100-200 thousand KIE, if necessary up to 500 thousand KIE (depending on the intensity bleeding).

With coagulopathies in combination with secondary hyperfibrinolysis appoint a dose of 1 million KIE and more.

During surgical interventions to prevent before, during and after operations - 200-400 thousand KII intravenously (slowly or drip), then during the next 2 days for 100 thousand KIE.

In obstetrical practice the initial dose is 1 million KIE, then every hour for 200 thousand KIE until the bleeding stops.

Perhaps a local application: gauze, soaked 100 thousand KIE, apply to the focus of bleeding.

With acute pancreatitis - 0.5-1 million KIE, followed by a decrease in 2-6 days. up to 50-300 thousand KIE before complete cancellation (after the disappearance of enzyme toxemia).

With exacerbation of chronic pancreatitis are introduced once at a rate of 25 thousand KIH per hour for 3-6 days; daily dose of 25-50 thousand KIE.

In the postoperative period and prophylactically (with the risk of injury to the pancreas), the initial dose is 200 thousand KIE, then within 2 days. after operations on 100 thousand KIE every 6 h.

Patients with acute necrosis of the pancreas and effusion into the abdominal cavity containing enzymes, aprotinin solution can additionally be administered intra-abdominally (in addition to intravenous administration).

Children

With violations of hemostasis aprotinin injected in a daily dose of 20 thousand KKE per kg of body weight.

Side effects:

Allergic reactions: bronchospasm, urticaria, pruritus, rhinitis, conjunctivitis, anaphylactic reactions (up to anaphylactic shock). From the side cardiovascular system: lowering of blood pressure, tachycardia. The use of large doses of aprotinin (8-12 million KIE) during repeated operations of bypass surgery on the coronary vessels of surgery may lead to an increased risk of myocardial infarction.

From the central nervous system: psychotic reactions, hallucinations, confusion.
From the digestive system: transient nausea, vomiting (with rapid administration).
Local reactions: thrombophlebitis at the site of administration (with prolonged administration).
Other: myalgia.

Overdose:

Symptoms: There may be an increase in the manifestations of the described side effects.

Treatment: conduct specific therapy. There is no specific antidote.

Interaction:

Pharmaceutically incompatible with other drugs (except for solutions of electrolytes and dextrose).

Inhibits the effects of fibrinolytic agents, incl. streptokinase, urokinase, alteplase.

Enhances the effect of heparin (the addition to heparinized blood causes increase in the coagulation time of whole blood).

Mutual reinforcement of action is noted with the joint appointment of aprotinin and preparations of dextran.

Special instructions:

Patients at increased risk development of allergic reactions before the use of Aprotinin is administered antihistamines preparations. In case of development Allergic reaction The administration of aprotinin should be stopped immediately. The risk of developing allergic reactions increases in patients with prior treatment with aprotinin (for 15 days and up to 6 months).

To detect the presence of hypersensitivity, a test should be carried out: At least 10 minutes prior to the first therapeutic dose, 1 ml (10,000 IU aprotinin) is administered intravenously. If you have any allergic reaction to the test dose, apply aprotinin it is impossible because of possible anaphylaxis.

With DVS-syndrome, the drug can be used only after removing all manifestations of ICE and against the background of preventive action of heparin.

Particular caution should be given to patients who received muscle relaxants 2-3 days before.

Application for extracorporeal circulation: When aprotinin is added to the blood containing heparin, clotting time, measured by Hemochron or another comparative method for activating the foreign surface, increases. Therefore, the time of activated clotting elongated as a result of treatment with large doses of aprotinin does not provide information on the actual level of heparin.

With extracorporeal circulation during heart operations in patients, receiving large doses of aprotinin, the time of activated clotting is recommended to be maintained at a level above 750 sec. The heparin level can be measured with a heparin-prothrombin titre test.

One way to ensure a sufficient amount of heparin in the system blood circulation is the administration of heparin according to a certain dosing regimen, taking into account the patient's body weight and duration by-pass.

The dose of protamine, designed to neutralize heparin, depends on the total dose of heparin, and not on the activated clotting time measured by hemochrom.

Available data on the use of the drug in pediatric cardiac surgery are few in number.

Effect on the ability to drive transp. cf. and fur:Data on the effect of the drug on the ability to drive and engage in activities that require increased concentration and speed psychomotor reactions, no.

Form release / dosage:

Solution for infusions 10 000 KIE / ml.

Packaging:10 ml or 50 ml in neutral glass bottles. For 1 bottle of 10 ml or 50 ml, along with the instructions for use are placed in a pack of cardboard. For 5, 10 or 25 bottles of 10 ml and 5 bottles of 50 ml together with the instruction for use are placed in a pack of cardboard with partitions.

For 20, 30, 50 or 80 bottles with an equal number of instructions for use are placed in a box of cardboard (for hospitals).

Storage conditions:

At a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:2 years. Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:LP-000658

Date of registration:28.09.2011

The owner of the registration certificate:LENS-PHARM, LLC LENS-PHARM, LLC Russia

Manufacturer: & nbsp

LENS-PHARM, LLC Russia

Information update date: & nbsp06.11.2014

Illustrated instructions

Instructions

Aprotex (Aprotex)