Components:
Method of action:
Treatment option:
Medically reviewed by Militian Inessa Mesropovna, PharmD. Last updated on 17.03.2022
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Prevention and treatment of haemorrhages due to general or local fibrinolysis in adults and children from one year.
Specific indications include:
- Haemorrhage caused by general or local fibrinolysis such as:
| - Menorrhagia and metrorrhagia, - Gastrointestinal bleeding, - Haemorrhagic urinary disorders, further to prostate surgery or surgical procedures affecting the urinary tract, |
- Ear Nose Throat surgery (adenoidectomy, tonsillectomy, dental extractions),
- Gynaecological surgery or disorders of obstetric origin,
- Thoracic and abdominal surgery and other major surgical intervention such as cardiovascular surgery,
- Management of haemorrhage due to the administration of a fibrinolytic agent.
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) Fimoplas 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) Fimoplas 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 Fimoplas is contraindicated in patients with severe renal impairment. For patients with mild to moderate renal impairment, the dosage of Fimoplas should be reduced according to the serum creatinine level:
| Serum creatinine | Dose IV | Administration | |
| μmol/l | mg/10 ml | ||
| 120 to 249 | 1.35 to 2.82 | 10 mg/kg BW | Every 12 hours |
| 250 to 500 | 2.82 to 5.65 | 10 mg/kg BW | Every 24 hours |
| > 500 | > 5.65 | 5 mg/kg BW | Every 24 hours |
Hepatic impairment
No dose adjustment is required in patients with hepatic impairment.
Paediatric Population:
The efficacy, posology and safety of Fimoplas 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) Fimoplasic 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) Fimoplasic 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 Fimoplasic acid is contraindicated in patients with severe renal impairment. For patients with mild to moderate renal impairment, the dosage of Fimoplasic acid should be reduced according to the serum creatinine level:
| Serum creatinine | Dose IV | Administration | |
| μmol/l | mg/10 ml | ||
| 120 to 249 | 1.35 to 2.82 | 10 mg/kg BW | Every 12 hours |
| 250 to 500 | 2.82 to 5.65 | 10 mg/kg BW | Every 24 hours |
| > 500 | > 5.65 | 5 mg/kg BW | Every 24 hours |
Hepatic impairment
No dose adjustment is required in patients with hepatic impairment.
Paediatric Population:
The efficacy, posology and safety of Fimoplasic 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.
Acute venous or arterial thrombosis.
Fibrinolytic conditions following consumption coagulopathy except in those with predominant activation of the fibrinolytic system with acute severe bleeding.
Severe renal impairment (risk of accumulation).
History of convulsions
Intrathecal and intraventricular injection, intracerebral application (risk of cerebral oedema and convulsions)
The indications and method of administration indicated above should be followed strictly:
- Intravenous injections should be given very slowly.
- Fimoplas should not be administered by the intramuscular route.
Convulsions
Cases of convulsions have been reported in association with Fimoplas treatment.In coronary artery bypass graft (CABG) surgery, most of these cases were reported following intravenous (i.v.) injection of Fimoplas 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), Fimoplas 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.
Fimoplas 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 Fimoplas. If Fimoplas 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 Fimoplas is frequently sufficient to control bleeding. Administration of Fimoplas 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.
- Fimoplasic acid should not be administered by the intramuscular route.
Convulsions
Cases of convulsions have been reported in association with Fimoplasic acid treatment.In coronary artery bypass graft (CABG) surgery, most of these cases were reported following intravenous (i.v.) injection of Fimoplasic 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), Fimoplasic 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.
Fimoplasic 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 Fimoplasic acid. If Fimoplasic 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 Fimoplasic acid is frequently sufficient to control bleeding. Administration of Fimoplasic acid in DIC should be considered only when appropriate haematological laboratory facilities and expertise are available.
No studies have been performed on the ability to drive and use machines.
The ADRs reported from clinical studies and post-marketing experience are listed below according to system organ class.
Tabulated list of adverse reactions
Adverse reactions reported are presented in table below. Adverse reactions are listed according to MedDRA primary system organ class. Within each system organ class, adverse reactions are ranked by frequency. Within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness. Frequencies were defined as follows: Very common (>1/10); common (>1/100 to <1/10); uncommon (>1/1,000 to <1/100), not known (cannot be estimated from the available data).
| MedDRA System Organ Class | Frequency | Undesirable Effects |
| Immune system disorders | Not known | - Hypersensitivity reactions including anaphylaxis |
| Nervous system disorders | Not known | <4) |
| Eye disorders | Not known | - Visual disturbances including impaired colour vision |
| Vascular disorders | Not known | - Malaise with hypotension with or without loss of consciousness (generally following a too fast intravenous injection, exceptionally after oral administration) - Arterial or venous embolism at any sites |
| Gastrointestinal disorders | Common | - Diarrhoea - Vomiting - Nausea |
| Skin and subcutaneous tissue disorders | Uncommon | - Dermatitis allergic |
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard.
No case of overdose has been reported.
Signs and symptoms may include dizziness, headache, hypotension, and convulsions. It has been shown that convulsions tend to occur at higher frequency with increasing dose.
Management of overdose should be supportive.
Pharmacotherapeutic group: Antihemorrhagics, Antifibrinolytics, Aminoacids
ATC code: B02AA02
Fimoplas exerts an anti haemorrhagic activity by inhibiting the fibrinolytic properties of plasmin.
A complex involving Fimoplas, plasminogen is constituted; the Fimoplas being linked to plasminogen when transformed into plasmin.
The activity of the Fimoplas-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 Fimoplas. Most of them were controlled versus placebo. Studied population was heterogenic in terms of age, surgery types, dosing schedules. Study results with Fimoplas 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
Fimoplasic acid exerts an anti haemorrhagic activity by inhibiting the fibrinolytic properties of plasmin.
A complex involving Fimoplasic acid, plasminogen is constituted; the Fimoplasic acid being linked to plasminogen when transformed into plasmin.
The activity of the Fimoplasic acid-plasmin complex on the activity on fibrin is lower than the activity of free plasmin alone.
In vitro studies showed that high Fimoplasic 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 Fimoplasic acid. Most of them were controlled versus placebo. Studied population was heterogenic in terms of age, surgery types, dosing schedules. Study results with Fimoplasic 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 Fimoplas are obtained rapidly after a short intravenous infusion after which plasma concentrations decline in a multi-exponential manner.
Distribution
The plasma protein binding of Fimoplas is about 3% at therapeutic plasma levels and seems to be fully accounted for by its binding to plasminogen. Fimoplas does not bind to serum albumin. The initial volume of distribution is about 9 to 12 litres.
Fimoplas passes through the placenta. Following administration of an intravenous injection of 10 mg/kg to 12 pregnant women, the concentration of Fimoplas in serum ranged 10-53 μg/mL while that in cord blood ranged 4-31 μg/mL. Fimoplas 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 Fimoplas 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). Fimoplas 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 Fimoplas is about 90% within the first 24 hours after intravenous administration of 10 mg/kg body weight. Elimination half-life of Fimoplas 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 Fimoplasic 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 Fimoplasic acid is about 3% at therapeutic plasma levels and seems to be fully accounted for by its binding to plasminogen. Fimoplasic acid does not bind to serum albumin. The initial volume of distribution is about 9 to 12 litres.
Fimoplasic acid passes through the placenta. Following administration of an intravenous injection of 10 mg/kg to 12 pregnant women, the concentration of Fimoplasic acid in serum ranged 10-53 μg/mL while that in cord blood ranged 4-31 μg/mL. Fimoplasic 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 Fimoplasic 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). Fimoplasic 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 Fimoplasic acid is about 90% within the first 24 hours after intravenous administration of 10 mg/kg body weight. Elimination half-life of Fimoplasic 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 Fimoplas.
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 Fimoplasic acid.
Fimoplas solution for injection should not be added to blood for transfusion, or to injections containing penicillin.
Fimoplasic acid solution for injection should not be added to blood for transfusion, or to injections containing penicillin.
The product is for single use only. Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
However, we will provide data for each active ingredient
