Amchafibrin 500 mg инструкция по применению

Posology

Adults

Unless otherwise prescribed, the following doses are recommended:

1. Standard treatment of local fibrinolysis:

0.5 g (1 ampoule of 5 ml) to 1 g (1 ampoule of 10 ml or 2 ampoules of 5 ml) Amchafibrin by slow intravenous injection (= 1 ml/minute) two to three times daily

2. Standard treatment of general fibrinolysis:

1 g (1 ampoule of 10 ml or 2 ampoules of 5 ml) Amchafibrin by slow intravenous injection (= 1 ml/minute) every 6 to 8 hours, equivalent to 15 mg/kg BW

Renal impairment

In renal insufficiency leading to a risk of accumulation, the use of Amchafibrin is contraindicated in patients with severe renal impairment. For patients with mild to moderate renal impairment, the dosage of Amchafibrin should be reduced according to the serum creatinine level:

Hepatic impairment

No dose adjustment is required in patients with hepatic impairment.

Paediatric Population:

The efficacy, posology and safety of Amchafibrin in children undergoing cardiac surgery have not been fully established.

Elderly:

No reduction in dosage is necessary unless there is evidence of renal failure.

Method of administration

The administration is strictly limited to slow intravenous injection.

Posology

Adults

Unless otherwise prescribed, the following doses are recommended:

1. Standard treatment of local fibrinolysis:

0.5 g (1 ampoule of 5 ml) to 1 g (1 ampoule of 10 ml or 2 ampoules of 5 ml) Amchafibrinic acid by slow intravenous injection (= 1 ml/minute) two to three times daily

2. Standard treatment of general fibrinolysis:

1 g (1 ampoule of 10 ml or 2 ampoules of 5 ml) Amchafibrinic acid by slow intravenous injection (= 1 ml/minute) every 6 to 8 hours, equivalent to 15 mg/kg BW

Renal impairment

In renal insufficiency leading to a risk of accumulation, the use of Amchafibrinic acid is contraindicated in patients with severe renal impairment. For patients with mild to moderate renal impairment, the dosage of Amchafibrinic acid should be reduced according to the serum creatinine level:

Hepatic impairment

No dose adjustment is required in patients with hepatic impairment.

Paediatric Population:

The efficacy, posology and safety of Amchafibrinic acid in children undergoing cardiac surgery have not been fully established.

Elderly:

No reduction in dosage is necessary unless there is evidence of renal failure.

Method of administration

The administration is strictly limited to slow intravenous injection.

The indications and method of administration indicated above should be followed strictly:

— Intravenous injections should be given very slowly.

— Amchafibrin should not be administered by the intramuscular route.

Convulsions

Cases of convulsions have been reported in association with Amchafibrin treatment.In coronary artery bypass graft (CABG) surgery, most of these cases were reported following intravenous (i.v.) injection of Amchafibrin in high doses. With the use of the recommended lower doses of TXA, the incidence of post-operative seizures was the same as that in untreated patients.

Visual disturbances

Attention should be paid to possible visual disturbances including visual impairment, vision blurred, impaired colour vision and if necessary the treatment should be discontinued. With continuous long-term use of TXA solution for injection, regular ophthalmologic examinations (eye examinations including visual acuity, colour vision, fundus, visual field etc.) are indicated. With pathological ophthalmic changes, particularly with diseases of the retina, the physician must decide after consulting a specialist on the necessity for the long-term use of TXA solution for injection in each individual case.

Haematuria

In case of haematuria from the upper urinary tract, there is a risk for urethral obstruction.

Thromboembolic events

Before use of TXA, risk factors of thromboembolic disease should be considered. In patients with a history of thromboembolic diseases or in those with increased incidence of thromboembolic events in their family history (patients with a high risk of thrombophilia), Amchafibrin solution for injection should only be administered if there is a strong medical indication after consulting a physician experienced in hemostaseology and under strict medical supervision.

Amchafibrin should be administered with care in patients receiving oral contraceptives because of the increased risk of thrombosis.

Disseminated intravascular coagulation

Patients with disseminated intravascular coagulation (DIC) should in most cases not be treated with Amchafibrin. If Amchafibrin is given it must be restricted to those in whom there is predominant activation of the fibrinolytic system with acute severe bleeding. Characteristically, the haematological profile approximates to the following: reduced euglobulin clot lysis time; prolonged prothrombin time; reduced plasma levels of fibrinogen, factors V and VIII, plasminogen fibrinolysin and alpha-2 macroglobulin; normal plasma levels of P and P complex; i.e. factors II (prothrombin), VIII and X; increased plasma levels of fibrinogen degradation products; a normal platelet count. The foregoing presumes that the underlying disease state does not of itself modify the various elements in this profile. In such acute cases a single dose of 1 g Amchafibrin is frequently sufficient to control bleeding. Administration of Amchafibrin in DIC should be considered only when appropriate haematological laboratory facilities and expertise are available.

The indications and method of administration indicated above should be followed strictly:

— Intravenous injections should be given very slowly.

— Amchafibrinic acid should not be administered by the intramuscular route.

Convulsions

Cases of convulsions have been reported in association with Amchafibrinic acid treatment.In coronary artery bypass graft (CABG) surgery, most of these cases were reported following intravenous (i.v.) injection of Amchafibrinic acid in high doses. With the use of the recommended lower doses of TXA, the incidence of post-operative seizures was the same as that in untreated patients.

Visual disturbances

Attention should be paid to possible visual disturbances including visual impairment, vision blurred, impaired colour vision and if necessary the treatment should be discontinued. With continuous long-term use of TXA solution for injection, regular ophthalmologic examinations (eye examinations including visual acuity, colour vision, fundus, visual field etc.) are indicated. With pathological ophthalmic changes, particularly with diseases of the retina, the physician must decide after consulting a specialist on the necessity for the long-term use of TXA solution for injection in each individual case.

Haematuria

In case of haematuria from the upper urinary tract, there is a risk for urethral obstruction.

Thromboembolic events

Before use of TXA, risk factors of thromboembolic disease should be considered. In patients with a history of thromboembolic diseases or in those with increased incidence of thromboembolic events in their family history (patients with a high risk of thrombophilia), Amchafibrinic acid solution for injection should only be administered if there is a strong medical indication after consulting a physician experienced in hemostaseology and under strict medical supervision.

Amchafibrinic acid should be administered with care in patients receiving oral contraceptives because of the increased risk of thrombosis.

Disseminated intravascular coagulation

Patients with disseminated intravascular coagulation (DIC) should in most cases not be treated with Amchafibrinic acid. If Amchafibrinic acid is given it must be restricted to those in whom there is predominant activation of the fibrinolytic system with acute severe bleeding. Characteristically, the haematological profile approximates to the following: reduced euglobulin clot lysis time; prolonged prothrombin time; reduced plasma levels of fibrinogen, factors V and VIII, plasminogen fibrinolysin and alpha-2 macroglobulin; normal plasma levels of P and P complex; i.e. factors II (prothrombin), VIII and X; increased plasma levels of fibrinogen degradation products; a normal platelet count. The foregoing presumes that the underlying disease state does not of itself modify the various elements in this profile. In such acute cases a single dose of 1 g Amchafibrinic acid is frequently sufficient to control bleeding. Administration of Amchafibrinic acid in DIC should be considered only when appropriate haematological laboratory facilities and expertise are available.

Pharmacotherapeutic group: Antihemorrhagics, Antifibrinolytics, Aminoacids

ATC code: B02AA02

Amchafibrin exerts an anti haemorrhagic activity by inhibiting the fibrinolytic properties of plasmin.

A complex involving Amchafibrin, plasminogen is constituted; the Amchafibrin being linked to plasminogen when transformed into plasmin.

The activity of the Amchafibrin-plasmin complex on the activity on fibrin is lower than the activity of free plasmin alone.

In vitro studies showed that high tranexamic dosages decreased the activity of complement.

Paediatric population

In children over one year old:

Literature review identified 12 efficacy studies in paediatric cardiac surgery which have included 1073 children, 631 having received Amchafibrin. Most of them were controlled versus placebo. Studied population was heterogenic in terms of age, surgery types, dosing schedules. Study results with Amchafibrin suggest reduced blood loss and reduced blood product requirements in paediatric cardiac surgery under cardiopulmonary bypass (CPB) where there is a high risk of haemorrhage, especially in cyanotic patients or patients undergoing repeat surgery.The most adapted dosing schedule appeared to be:

— first bolus of 10 mg/kg after induction of anaesthesia and prior to skin incision,

— continuous infusion of 10 mg/kg/h or injection into the CPB pump prime at a dose adapted on the CPB procedure, either according to a patient weight with a dose of 10 mg/kg dose, either according to CPB pump prime volume, last injection of 10 mg/kg at the end of CPB.

While studied in very few patients, the limited data suggest that continuous infusion is preferable, since it would maintain therapeutic plasma concentration throughout surgery.

No specific dose-effect study or PK study has been conducted in children.

Pharmacotherapeutic group: Antihemorrhagics, Antifibrinolytics, Aminoacids

ATC code: B02AA02

Amchafibrinic acid exerts an anti haemorrhagic activity by inhibiting the fibrinolytic properties of plasmin.

A complex involving Amchafibrinic acid, plasminogen is constituted; the Amchafibrinic acid being linked to plasminogen when transformed into plasmin.

The activity of the Amchafibrinic acid-plasmin complex on the activity on fibrin is lower than the activity of free plasmin alone.

In vitro studies showed that high Amchafibrinic dosages decreased the activity of complement.

Paediatric population

In children over one year old:

Literature review identified 12 efficacy studies in paediatric cardiac surgery which have included 1073 children, 631 having received Amchafibrinic acid. Most of them were controlled versus placebo. Studied population was heterogenic in terms of age, surgery types, dosing schedules. Study results with Amchafibrinic acid suggest reduced blood loss and reduced blood product requirements in paediatric cardiac surgery under cardiopulmonary bypass (CPB) where there is a high risk of haemorrhage, especially in cyanotic patients or patients undergoing repeat surgery.The most adapted dosing schedule appeared to be:

— first bolus of 10 mg/kg after induction of anaesthesia and prior to skin incision,

— continuous infusion of 10 mg/kg/h or injection into the CPB pump prime at a dose adapted on the CPB procedure, either according to a patient weight with a dose of 10 mg/kg dose, either according to CPB pump prime volume, last injection of 10 mg/kg at the end of CPB.

While studied in very few patients, the limited data suggest that continuous infusion is preferable, since it would maintain therapeutic plasma concentration throughout surgery.

No specific dose-effect study or PK study has been conducted in children.

Absorption

Peak plasma concentrations of Amchafibrin are obtained rapidly after a short intravenous infusion after which plasma concentrations decline in a multi-exponential manner.

Distribution

The plasma protein binding of Amchafibrin is about 3% at therapeutic plasma levels and seems to be fully accounted for by its binding to plasminogen. Amchafibrin does not bind to serum albumin. The initial volume of distribution is about 9 to 12 litres.

Amchafibrin passes through the placenta. Following administration of an intravenous injection of 10 mg/kg to 12 pregnant women, the concentration of Amchafibrin in serum ranged 10-53 μg/mL while that in cord blood ranged 4-31 μg/mL. Amchafibrin diffuses rapidly into joint fluid and the synovial membrane. Following administration of an intravenous injection of 10 mg/kg to 17 patients undergoing knee surgery, concentrations in the joint fluids were similar to those seen in corresponding serum samples. The concentration of Amchafibrin in a number of other tissues is a fraction of that observed in the blood (breast milk, one hundredth; cerebrospinal fluid, one tenth; aqueous humor, one tenth). Amchafibrin has been detected in semen where it inhibits fibrinolytic activity but does not influence sperm migration.

Excretion

It is excreted mainly in the urine as unchanged drug. Urinary excretion via glomerular filtration is the main route of elimination. Renal clearance is equal to plasma clearance (110 to 116 mL/min). Excretion of Amchafibrin is about 90% within the first 24 hours after intravenous administration of 10 mg/kg body weight. Elimination half-life of Amchafibrin is approximately 3 hours.

Special populations

Plasma concentrations increase in patients with renal failure.

No specific PK study has been conducted in children.

Absorption

Peak plasma concentrations of Amchafibrinic acid are obtained rapidly after a short intravenous infusion after which plasma concentrations decline in a multi-exponential manner.

Distribution

The plasma protein binding of Amchafibrinic acid is about 3% at therapeutic plasma levels and seems to be fully accounted for by its binding to plasminogen. Amchafibrinic acid does not bind to serum albumin. The initial volume of distribution is about 9 to 12 litres.

Amchafibrinic acid passes through the placenta. Following administration of an intravenous injection of 10 mg/kg to 12 pregnant women, the concentration of Amchafibrinic acid in serum ranged 10-53 μg/mL while that in cord blood ranged 4-31 μg/mL. Amchafibrinic acid diffuses rapidly into joint fluid and the synovial membrane. Following administration of an intravenous injection of 10 mg/kg to 17 patients undergoing knee surgery, concentrations in the joint fluids were similar to those seen in corresponding serum samples. The concentration of Amchafibrinic acid in a number of other tissues is a fraction of that observed in the blood (breast milk, one hundredth; cerebrospinal fluid, one tenth; aqueous humor, one tenth). Amchafibrinic acid has been detected in semen where it inhibits fibrinolytic activity but does not influence sperm migration.

Excretion

It is excreted mainly in the urine as unchanged drug. Urinary excretion via glomerular filtration is the main route of elimination. Renal clearance is equal to plasma clearance (110 to 116 mL/min). Excretion of Amchafibrinic acid is about 90% within the first 24 hours after intravenous administration of 10 mg/kg body weight. Elimination half-life of Amchafibrinic acid is approximately 3 hours.

Special populations

Plasma concentrations increase in patients with renal failure.

No specific PK study has been conducted in children.

Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential and toxicity to reproduction.

Epileptogenic activity has been observed in animals with intrathecal use of Amchafibrin.

Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential and toxicity to reproduction.

Epileptogenic activity has been observed in animals with intrathecal use of Amchafibrinic acid.