1. Name of the medicinal product

Tranexamic Acid Injection BP 500mg/5ml Taj Pharma
Tranexamic Acid Injection BP 1000mg/10ml Taj Pharma

2. Qualitative and quantitative composition

a) Tranexamic Acid Injection BP 500mg/5ml
Each ml Contains:
Tranexamic acid BP                           100mg

b) Tranexamic Acid Injection BP 1000mg/10ml
Each ml Contains:
Tranexamic acid BP                           100mg

For the full list of excipients, see section 6.1.

  1. Pharmaceutical form

Solution for injection.

Colourless solution.

  1. Clinical particulars

4.1 Therapeutic indications

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.

4.2 Posology and method of administration

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) tranexamic acid by slow intravenous injection (= 1 ml/minute) two to three times daily

  1. Standard treatment of general fibrinolysis:

1 g (1 ampoule of 10 ml or 2 ampoules of 5 ml) tranexamic 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 tranexamic acid is contra-indicated in patient with severe renal impairment (see section 4.3). For patient with mild to moderate renal impairment, the dosage of tranexamic 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 patient with hepatic impairment.

Paediatric Population:

In children from 1 year, for current approved indications as described in section 4.1, the dosage is in the region of 20 mg/kg/day. However, data on efficacy, posology and safety for these indications are limited.

The efficacy, posology and safety of tranexamic acid in children undergoing cardiac surgery have not been fully established. Currently available data are limited and are described in section 5.1.

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.

4.3 Contraindications

  • Hypersensitivity to the active substance or to any of the excipients listed in section 6.1;
  • Acute venous or arterial thrombosis (see section 4.4);
  • Fibrinolytic conditions following consumption coagulopathy except in those with predominant activation of the fibrinolytic system with acute severe bleeding (see section 4.4);
  • Severe renal impairment (risk of accumulation);
  • History of convulsions;
  • Intrathecal and intraventricular injection, intracerebral application (risk of cerebral oedema and convulsions).

4.4 Special warnings and precautions for use

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

  • Intravenous injections should be given very slowly
  • Tranexamic acid should not be administered by the intramuscular route.

Convulsions

Cases of convulsions have been reported in association with tranexamic acid treatment. In coronary artery bypass graft (CABG) surgery, most of these cases were reported following intravenous (i.v.) injection of tranexamic 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), Tranexamic 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 (see section 4.3).

Tranexamic acid should be administered with care in patients receiving oral contraceptives because of the increased risk of thrombosis (See section 4.5.).

Disseminated intravascular coagulation

Patients with disseminated intravascular coagulation (DIC) should in most cases not be treated with tranexamic acid (see section 4.3). If tranexamic 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 1g tranexamic acid is frequently sufficient to control bleeding.. Administration of Tranexamic acid in DIC should be considered only when appropriate haematological laboratory facilities and expertise are available.

4.5 Interaction with other medicinal products and other forms of interaction

No interaction studies have been performed. Simultaneous treatment with anticoagulants must take place under the strict supervision of a physician experienced in this field. Medicinal products that act on haemostasis should be given with caution to patients treated with tranexamic acid. There is a theoretical risk of increased thrombus-formation potential, such as with oestrogens. Alternatively, the antifibrinolytic action of the drug may be antagonised with thrombolytic drugs.

4.6 Fertility, pregnancy and lactation

Women of childbearing potential have to use effective contraception during treatment.

Pregnancy

There are insufficient clinical data on the use of tranexamic acid in pregnant women. As a result, although studies in animals do not indicate teratogenic effects, as a 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.

Breastfeeding

Tranexamic acid is excreted in human milk. Therefore, breastfeeding is not recommended.

Fertility

There are no clinical data on the effects of tranexamic acid on human fertility.

4.7 Effects on ability to drive and use machines

No studies have been performed on the ability to drive and use machines.

4.8 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. Frequencies were defined as follows: Common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100), not known (can not be estimated from the available data).

MedDRA

System Organ Class

Frequency Undesirable Effects
Skin and subcutaneous tissues disorders Uncommon – Dermatitis allergic
Gastrointestinal disorders Common – Diarrhoea

– Vomiting

– Nausea

Nervous system disorders Not known – Convulsions particularly in case of misuse (refer to sections 4.3 and 4.4)
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 thrombosis at any sites

Immune system disorders Not known – Hypersensitivity reactions including anaphylaxis

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important.

4.9 Overdose

No cases of overdose have 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.

  1. Pharmacological properties

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Antihemorrhagics, Antifibrinolytics, Aminoacids

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 when 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 patient weight with a 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 liters.

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 μg/mL while that in cord blood ranged 4-31 μg/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 urineas 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. Half-life of tranexamic acid is approximately 3 hours.

Special populations

Plasma concentrations increase in patients with renal failure.

No specific PK 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 and toxicity to reproduction. Epileptogenic activity has been observed in animals with intrathecal use of tranexamic acid.

  1. Pharmaceutical particulars

6.1 List of excipients

Water for injections

6.2 Incompatibilities

This medicinal product must not be mixed with other medicinal products.

6.3 Shelf life

30 months

Use immediately. Discard any unused portion

6.4 Special precautions for storage

Do not store above 25°C. Store in the original packaging. Do not refrigerate or freeze.

6.5 Nature and contents of container

Type I clear glass 5ml ampoules packed in outer cardboard carton.

Pack size: 10 ampoules.

6.6 Special precautions for disposal and other handling

No special requirements.

For single use only. Any portion of unused ampoule should be discarded.

7.Manufactured in India by:
TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of  Commerce Lane,
Fort, Mumbai – 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
E-mail: tajgroup@tajpharma.com

Tranexamic Acid Injection BP 500mg/5ml, 1000mg/10ml

Package leaflet: information for the patient

Tranexamic Acid Injection BP 500mg/5ml Taj pharma

Read all of this leaflet carefully before you, or your child, are given this medicine because it contains important information for you.

  • Keep this leaflet. You may need to read it again.
  • If you have any further questions, ask your doctor or nurse.
  • If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet:

  1. What Tranexamic Acid Solution for Injection is and what it is used for
    2. What you need to know before you are given Tranexamic Acid Solution for Injection
    3. How Tranexamic Acid Solution for Injection is given
    4. Possible side effects
    5. How to store Tranexamic Acid Solution for Injection
    6. Contents of the pack and other information
  2. What Tranexamic Acid Solution for Injection is and what it is used for

Tranexamic Acid 500mg/5ml Solution for Injection (called Tranexamic Acid Solution for Injection throughout the rest of this leaflet) contains tranexamic acid which belongs to a group of medicines called antihaemorragics; antifibrinolytics, aminoacids. Tranexamic acid is used in adults and children above one year of age for the prevention and treatment of bleeding due to a process that inhibits blood clotting called fibrinolysis.

Specific uses include:

  • heavy periods in women;
  • gastrointestinal bleeding;
  • haemorrhagic urinary disorders after having an operation on your prostate gland or urinary tract;
  • after having an operation on your ear, nose or throat;
  • after having heart, abdominal or gynaecological surgery;
  • bleeding after you have been treated with another medicine to break down blood clots.
  1. What you need to know before you are given Tranexamic Acid Solution for Injection

Do not have Tranexamic Acid Solution for Injection if you:

  • are allergic (hypersensitive) to tranexamic acid or any of the other ingredients of this medicine (see section 6, Other information);
  • currently have or have ever had a disease leading to blood clots;
  • have a condition called “consumption coagulopathy” where blood in the whole body starts to clot;
  • have kidney problems;
  • have a history of convulsions (fits).

Due to the risk of fits or swelling in the brain, injection into the spinal cord, directly into the heart or into the brain is not recommended.

If you think any of these apply to you, or if you are in any doubt at all, tell your doctor before you are given Tranexamic Acid Solution for Injection.

Warnings and precautions

Tell your doctor if any of the following apply to you, to help him or her decide if Tranexamic Acid Solution for Injection is suitable for you:

  • if you have had blood in your urine, which could indicate that there is a clot in your upper urinary tract;
  • if you are at risk of having blood clots;
  • if you suffer from excessive clotting or bleeding throughout your body (disseminated intravascular coagulation). Your doctor may carry out a blood test to see if the process that inhibits blood clotting (called fibrinolysis) is activated;
  • if you have had convulsions (fits). Your doctor will use the minimum dose possible to avoid further convulsions after the treatment;
  • if you are on long term treatment with Tranexamic Acid Solution for Injection pay attention to any possible disturbances in your colour vision. If necessary, your doctor may discontinue the treatment. With continuous, long term use of Tranexamic Acid Solution for Injection regular eye tests are recommended. If changes are seen in your eyes, your doctor may consult an eye specialist in order to decide whether to continue your treatment.

Other medicines and Tranexamic Acid Solution for Injection

Please tell your doctor or nurse if you are taking, or have recently taken, or might take any other medicines, including medicines obtained without a prescription.

You should specifically tell your doctor if you take:

  • Other medicines that help blood to clot, called antifibrinolytic medicines;
  • Medicines that prevent blood clotting, called thrombolytic medicines;
  • Oral contraceptives.

Pregnancy, breast-feeding and fertility

  • Ask your doctor for advice if you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby.
  • Tranexamic acid is excreted in breast milk. Therefore, the use of Tranexamic Acid Solution for Injection during breast-feeding is not recommended.

Driving and using machines

No studies have been performed on the ability to drive and use machines.

  1. How Tranexamic Acid Solution for Injection is given

Tranexamic Acid Solution for Injection will be given to you by a slow injection into your vein. Your doctor will decide the correct dose for you and how long you should take it.

Use in Adults

  • Treatment of Local Fibrinolysis:
    The usual dose is 500-1000mg (5-10ml) three times a day. This will usually be given by a slow injection into your vein.
  • Treatment of General Fibrinolysis:
    The usual dose is 1000mg (10ml) every 6 to 8 hours, or up to 15mg per kg of body weight.

Use in Children

  • The doctor will decide the right dose to give your child and how long he or she should take it.
  • If Tranexamic Acid Solution for Injection is given to a child over one year old, the dose will be based on the child’s body weight.

Use in Elderly

No reduction in dose is necessary unless you have kidney problems.

Use in Patients with Kidney Problems

If you have problems with your kidneys, the dose may be reduced. Your doctor will decide what dose to give you based on a blood test.

Use in Patients with Liver Problems

No reduction in dose is necessary.

Method of Administration

Tranexamic Acid Solution for Injection should only be injected slowly into a vein. It should not be injected into a muscle.

If you are given too much Tranexamic Acid Solution for Injection

If you are given too much Tranexamic Acid Solution for Injection, you may experience temporary low blood pressure (you may feel faint or dizzy on standing). Talk to your doctor or nurse immediately.

  1. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

If you experience any of the following side effects after you have been given your medicine, tell your doctor immediately. If you are not in hospital, you MUST GO straight away.

These side effects are rare but serious.

  • Severe allergic reactionwhich may include a red and lumpy skin rash, difficulty breathing, swelling of face, mouth, lips or eyelids, unexplained high temperature (fever) and feeling faint.
    If the swelling affects your throat and makes breathing and swallowing difficult, go to hospital straight away.
  • Symptoms of a blood clotwhich may include swelling or pain in your legs or chest, headache, weakness of the face and limbs on one side of the body.

Other side effects which may occur:

Common (may affect up to 1 in 10 users)

  • feeling sick;
  • being sick;

Uncommon (may affect up to 1 in 1000 users)

Not known (the frequency cannot be estimated from the available data)

  • low blood pressure (you may feel generally unwell, faint or dizzy on standing) which is usually caused by an injection being given too quickly;
  • fits;
  • visual disturbances, including colour disturbance.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or nurse.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet.

  1. How to store Tranexamic Acid Solution for Injection

Do not store above 25°C. Store in the original packaging. Do not refrigerate or freeze.

Tranexamic Acid Solution for Injection will be stored by your doctor, nurse or pharmacist, out of the sight and reach of children.

Tranexamic Acid Solution for Injection should not be used after the expiry date stated on the carton and vial label. The expiry date refers to the last day of that month.

This product is for single use only. Once your doctor or nurse has opened the vial, it should be used immediately. Any remaining Tranexamic Acid Solution for Injection must be thrown away by the doctor or nurse.

  1. Contents of the pack and other information

What Tranexamic Acid Solution for Injection contains

  • The active substance is tranexamic acid. Each 5ml vial contains 500mg tranexamic acid (100mg per ml).
  • The other ingredient is water for injections.

What Tranexamic Acid Solution for Injection looks like and contents of the pack

This medicine is a clear, colourless solution in a clear, glass vial. Each vial contains 5ml of medicine. This product is available in cartons containing 10 x 5ml vials.

7.Manufactured in India by:
TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of  Commerce Lane,
Fort, Mumbai – 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
E-mail: tajgroup@tajpharma.com