Klotigo 500 mg,1 000 mg Solution for injection/ infusion

u2022 Short term use in the treatment of haemorrhage or risk of haemorrhage in increased fibrinolysis or fibrinogenolysis. Local fibrinolysis occurs in the following conditions:

• prostatectomy and bladder surgery
• epistaxis
• conisation of the cervix
• traumatic hyphaema.

u2022 Management of dental extraction in haemophiliacs.

u2022 Hereditary angioedema.

u2022 Menorrhagia.

Posology

Adults

Administration by injection is normally changed to oral administration of an oral dosage form of tranexamic acid after a few days.

Haemorrhage or risk of haemorrhage in increased fibrinolysis or fibrinogenolysis

Standard treatment of local fibrinolysis

0,5 g (1 ampoule of 5 mL) to 1 g (2 ampoules of 5 mL) KLOTIGO by slow intravenous injection (IV) or infusion (= 1 mL/minute) two to three times daily

Standard treatment of general fibrinolysis

1 g (2 ampoules of 5 mL) KLOTIGO by slow intravenous injection or infusion (= 1 mL/minute) every 6 to 8 hours, equivalent to 15 mg/kg body weight (BW).

Prostatectomy and bladder surgery

0,5 g (1 ampoule of 5 mL) to 1 g (2 ampoules of 5 mL) KLOTIGO by slow intravenous injection or infusion (1 mL/min), 2 - 3 times daily (the first injection being given during the operation)/ for the first three days after surgery.

Epistaxis

1,0 g to 1,5 g every 8 - 12 hours for 10 days.

Conisation of the cervix

1,0 g to 1,5 g every 8 to 12 hours for 12 days post-operatively.

Traumatic hyphaemia:

1,0 to 1,5 g every 8 hours for six to seven days.

Dental operations/extractions in haemophiliacs:

Two hours before the operation, 25 mg/kg of KLOTIGO is given, as well as Factor VIII and Factor IX. After the operation, tranexamic acid at a dosage of 25 mg/kg is given three to four times a day for 6 to 8 days (normally as an oral dosage form).

Hereditary angioedema:

Some patients are aware of the onset of illness; a suitable treatment for these patients is 1,0 - 1,5 g two to three times daily for some days. Other patients are treated continually at this dosage.

Menorrhagia:

1,0 - 1,5 g three to four times daily (normally as an oral dosage form), given at the onset of heavy bleeding for the duration of the period.

Special populations

Renal impairment

For patients with impaired renal function, KLOTIGO should be given with caution (see section 4.4). Dosages should be reduced in patients with renal impairment.

For patients with moderate to severe impaired renal function, the following dosages are recommended:

Serum creatinine (micromole/L) Intravenous dose

120 - 250 10 mg/kg body weight twice daily

250 - 500 10 mg/kg body weight daily

> 500 5 mg/kg body weight daily

Paediatric population

Data on efficacy and safety in children are limited.

Method of administration

KLOTIGO solution for injection is strictly limited to slow intravenous infusion (see section 6.6), or slow injection over a period of at least five minutes, i.e. 1 mL/minute (see sections 4.3 and 4.4).

For intravenous injection, use immediately after opening. Diluted infusion solutions are stable in the refrigerator at 2 - 8 u00b0C for up to 24 hours (see section 6.3).

u2022 Hypersensitivity to tranexamic acid or to any of the ingredients of KLOTIGO (see section 6.1)

In cases of massive upper urinary tract haemorrhage, KLOTIGO should be avoided to reduce the risk of ureteric obstruction.

u2022 patients with pronounced thrombotic tendency or colour vision disorder (see section 4.4)

u2022 thrombophlebitis, impaired liver function and subarachnoid bleeding

u2022 fibrinolytic conditions following consumption coagulopathy except in those with predominant activation of the fibrinolytic system with acute severe bleeding (see section 4.4)

u2022 history of convulsions

u2022 history of acute venous or arterial thrombosis (see section 4.4)

u2022 severe renal impairment (risk of accumulation)

u2022 active intravascular clotting

u2022 intrathecal and intraventricular injection, intracerebral application (risk of cerebral oedema and convulsions).

The indications for use and method of administration should be followed strictly:

u2022 intravenous injections should be given very slowly (maximum 1 mL per minute)

u2022 KLOTIGO must not be administered by the intramuscular route

u2022 KLOTIGO must not be administered by intrathecal or intraventricular injection, or intracerebral application due to a risk of cerebral oedema and convulsions.

Convulsions

Convulsions have been reported in association with tranexamic acid, as in KLOTIGO, treatment. In coronary artery bypass graft (CABG) surgery, most of these cases were reported following intravenous (IV) injection of tranexamic acid, as in KLOTIGO, in high doses.

With the use of the recommended lower doses of KLOTIGO, the incidence of post-operative seizures was the same as that in untreated patients.

Visual disturbances

The patient should be monitored for visual disturbances, including visual impairment, blurred vision, impaired colour vision. If necessary, KLOTIGO should be discontinued.

With continuous long-term use of KLOTIGO, regular ophthalmologic examinations (eye examinations including visual acuity, colour vision, fundus, visual field etc.) are indicated (see section 4.3). With pathological ophthalmic changes, particularly with diseases of the retina, it is recommended that the medical practitioner consult a specialist on the necessity for long-term use of KLOTIGO in each individual case.

Haematuria

In case of haematuria from the upper urinary tract, there is a risk for urethral obstruction (see section 4.3).

Thromboembolic events

Before use of KLOTIGO, 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 an elevated risk of thrombophilia), KLOTIGO is contraindicated (see section 4.3).

KLOTIGO 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 not be treated with KLOTIGO (see section 4.3). If KLOTIGO is given it should be restricted to those in whom there is predominant activation of the fibrinolytic system with acute severe bleeding.

Patients with menorrhagia (irregular menstrual bleeding) should not use KLOTIGO until the cause of the irregularity has been established.

Tranexamic acid should not be administered concomitantly with Factor IX Complex Concentrates or Anti-inhibitor Coagulant Concentrates, as the risk of thrombosis may be increased.

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 KLOTIGO is frequently sufficient to control bleeding. Administration of KLOTIGO in DIC should be considered only when appropriate haematological laboratory facilities and expertise are available.

Patients with a previous history of thromboembolic disease should not be given KLOTIGO unless simultaneous treatment with anticoagulants can be given (see section 4.3).

Liver function

Liver function tests should be performed if KLOTIGO is used long-term (see section 4.3).

Renal impairment

For patients in renal failure, KLOTIGO should be given with caution because of the risk of accumulation. Dosage should be reduced in patients with renal impairment (see section 4.2).

No studies of interactions between KLOTIGO and other medicines have been conducted.

Medicines with actions on haemostasis should be given with caution to patients on KLOTIGO.

Simultaneous treatment with anticoagulants should take place under the strict supervision of a doctor with experience in this field.

There is a risk of increased thrombus-formation potential such as with oestrogens.

Alternatively, the antifibrinolytic action of KLOTIGO may be antagonised with thrombolytic medicines.

Women of childbearing potential

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

Pregnancy

The safety of KLOTIGO has not been established in pregnancy.

Breastfeeding

Tranexamic acid passes into breast milk at a concentration of one hundredth of the corresponding serum levels. Therefore, breastfeeding is not recommended.

Fertility

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

No studies have been performed on the ability to drive and use machines. Side effects of KLOTIGO include visual disturbances and dizziness. Patients should be advised against driving and handling machinery if they develop these symptoms.

Tabulated list of adverse effects

System Organ Class Frequency Side effects

Immune system disorders Frequency unknown Hypersensitivity reactions including anaphylaxis

Nervous system disorders Frequency unknown Dizziness (giddiness), convulsions, particularly in case of misuse (see sections 4.3 and 4.4)

Eye disorders Less frequent Visual disturbances including impaired colour vision (see section 4.4)

Cardiac disorders Less frequent Thromboembolic events

Vascular disorders Less frequent Malaise with hypotension, with or without loss of consciousness (generally following a too fast intravenous injection), arterial or venous thrombosis at any sites, thrombotic complications due to inappropriate use

Gastrointestinal disorders Frequent Diarrhoea, vomiting, nausea

Skin and subcutaneous tissue disorders Less frequent Dermatitis allergic

Musculoskeletal, connective tissue and bone disorders Frequency unknown Musculoskeletal pain

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Healthcare professionals are requested to report any suspected adverse drug reactions to SAHPRA via the Med Safety APP (Medsafety X SAHPRA) and eReporting platform (who-umc.org) found on SAHPRA website. An email can be sent directly to the company, [email protected] , to ensure safety of the product.

Signs and symptoms: Dizziness, headache, nausea, vomiting, diarrhoea and convulsions. It has been shown that convulsions tend to occur at higher frequency with increasing dose. Faintness and hypotension may occur.

Management of overdose: Treatment would consist of enhancing diuresis (with fluids plus diuretics) activated charcoal therapy and symptomatic treatment.