Summary of medicine characteristics - TRANEXAMIC ACID PFIZER 100 MG / ML SOLUTION FOR INJECTION
1. NAME OF THE MEDICINAL PRODUCT
Tranexamic acid Pfizer 100 mg/mL solution for injection
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Each 5 mL ampoule contains 500 mg tranexamic acid.
For the full list of excipients, see section 6.1.
3. PHARMACEUTICAL FORM
Solution for injection/infusion.
Clear, colourless solution with pH of 6.5– 8.0.
4. CLINICAL PARTICULARS
4.1 Therapeutic indications
4.2 Posology and method of administration
4.3 Contraindications
4.6 Fertility, pregnancy and lactation
Women of childbearing potential
Women of childbearing potential have to use effective contraception during treatment.
Pregnancy
There are no or limited amount of data from the use of tranexamic acid in pregnant women. As a result, although studies in animals do not indicate teratogenic effects, as precaution for use, tranexamic acid is not recommended during the first trimester of pregnancy.
Limited clinical data on the use of tranexamic acid in different clinical haemorrhagic settings during the second and third trimesters did not identify deleterious effect for the foetus.
Tranexamic acid should be used throughout pregnancy only if the expected benefit justifies the potential risk.
Breast-feeding
Tranexamic acid is excreted in human milk. Therefore, breast-feeding is not recommended.
Fertility
There are no clinical data on the effects of tranexamic acid on fertility.
4.7 Effects on ability to drive and use machines
No studies have been performed on the ability to drive and use machines.
4. CLINICAL PARTICULARS
4.8 Undesirable effects
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.
| System organ class | Common > 1/100 to < 1/10 | Uncommon > 1/1,000 to < 1/100 | Frequency not known (cannot be estimated from the available data) |
| Immune system disorders | – Hypersensitivity reactions including anaphylaxis | ||
| Nervous system disorders | – Convulsions particularly in case of misuse (see sections 4.3 and 4.4) | ||
| Eye disorders | – Visual disturbances including impaired colour vision | ||
| Vascular disorders | – Malaise with hypotension, with or without loss of consciousness (generally following a too fast intravenous injection, exceptionally after oral administration) – Arterial or venous thrombosis at any sites | ||
| Gastrointestinal disorders | – Diarrhoea – Vomiting – Nausea | ||
| Skin and subcutaneous tissue disorders | – 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 the Yellow Card Scheme at www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
4.9 Overdose
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.
5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Antihaemorrhagics, Antifibrinolytics, Aminoacids ATC code: B02AA02
Tranexamic acid exerts an anti haemorrhagic activity by inhibiting the fibrinolytic properties of plasmin.
A complex involving tranexamic acid, plasminogen is constituted; the tranexamic acid being linked to plasminogen when transformed into plasmin.
The activity of the tranexamic acid-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 tranexamic acid. Most of them were controlled versus placebo. Studied population was heterogenic in terms of age, surgery types, dosing schedules. Study results with tranexamic 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.
5.2 Pharmacokinetic properties
Absorption
Peak plasma concentrations of tranexamic 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 tranexamic acid is about 3% at therapeutic plasma levels and seems to be fully accounted for by its binding to plasminogen. Tranexamic acid does not bind to serum albumin. The initial volume of distribution is about 9 to 12 litres.
Tranexamic acid passes through the placenta. Following administration of an intravenous injection of 10 mg/kg to 12 pregnant women, the concentration of tranexamic acid in serum ranged 10–53 microgram/mL while that in cord blood ranged 4–31 microgram/mL. Tranexamic 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 tranexamic 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). Tranexamic acid has been detected in semen where it inhibits fibrinolytic activity but does not influence sperm migration.
Elimination
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 tranexamic acid is about 90% within the first 24 hours after intravenous administration of 10 mg/kg body weight. Elimination half-life of tranexamic acid is approximately 3 hours.
Other special populations
Plasma concentrations increase in patients with renal failure.
No specific pharmacokinetic study has been conducted in children.
5.3 Preclinical safety data
Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, toxicity to reproduction and development. Epileptogenic activity has been observed in animals with intrathecal use of tranexamic acid.
6. PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Water for injections.
6. PHARMACEUTICAL PARTICULARS
6.2 Incompatibilities
This medicinal product should not be mixed with blood for transfusion or with solutions containing penicillin.
6. PHARMACEUTICAL PARTICULARS