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

• Short term use in the treatment of hyphaema and in patients with established coagulopathies who are undergoing minor surgery.
• Management of dental extraction in haemophiliacs.
• Hereditary angioedema.
• Menorrhagia.

Posology

Adults

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

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

Patients with established coagulopathies undergoing minor surgery: Conisation of the cervix: 1,0 to 1,5 g every 8 to 12 hours postoperatively.

Dental operations/extractions in haemophiliacs: Two hours before the operation, 25 mg/kg of HEMOPRON is given, as well as Factor VIII and Factor IX. After the operation, tranexamic acid at a dosage of 25 mg/kg is given 3 to 4 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.

Renal impairment

For patients with impaired renal function, HEMOPRON 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

Children

Data on efficacy and safety in children are limited.

Administration

HEMOPRON 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.

• Hypersensitivity to tranexamic acid, or to any of the excipients of HEMOPRON.
• In cases of massive upper urinary tract haemorrhage, HEMOPRON should be avoided to reduce the risk of ureteric obstruction.
• Patients with a pronounced thrombotic tendency or colour vision disorder (see section 4.4).
• Thrombophlebitis, impaired liver function and subarachnoid bleeding.
• Fibrinolytic conditions following consumption coagulopathy except in those with predominant activation of the fibrinolytic system with acute severe bleeding (see section 4.4).
• History of convulsions.

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

• Intravenous injections should be given very slowly.
• HEMOPRON must not be administered by the intramuscular route.
• Intrathecal and intraventricular injection, intracerebral application (risk of cerebral oedema and convulsions).

Convulsions

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

Visual disturbances

The patient should be monitored for visual disturbances, including visual impairment, blurred vision, impaired colour vision. If necessary, HEMOPRON should be discontinued. With continuous long-term use of HEMOPRON, 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 HEMOPRON 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 HEMOPRON, 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), HEMOPRON should not be administered (see section 4.3). HEMOPRON 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 HEMOPRON (see section 4.3). If HEMOPRON 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 HEMOPRON until the cause of irregularity has been established. Tranexamic acid should not be concomitantly administered with Factor IX Complex Concentrate or Anti-inhibitor Coagulant Concentrate, 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 HEMOPRON is frequently sufficient to control bleeding. Administration of HEMOPRON 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 HEMOPRON unless simultaneous treatment with anticoagulants can be given (see section 4.3).

Liver function

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

Renal impairment

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

Medicines with actions on haemostasis should be given with caution to patients on HEMOPRON. 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 HEMOPRON 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 HEMOPRON has not been established in pregnancy.

Breastfeeding

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

Fertility

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

Side effects of HEMOPRON include visual disturbances and dizziness. Patients should be advised against driving and handling machinery if they develop these symptoms.

Tabulated list of adverse reactions

System organ class

Frequent

Less frequent

Frequency not known

• Immune system disorders: Hypersensitivity reactions including anaphylaxis
• Nervous system disorders: Dizziness, convulsions particularly in case of misuse (see sections 4.3 and 4.4)
• Eye disorders: Retinal/arterial occlusion, Visual disturbances including impaired colour vision (see section 4.4)
• Vascular disorders: Thromboembolic events, Malaise with hypotension, with or without loss of consciousness (generally following a too fast intravenous injection), Arterial or venous thrombosis at any sites
• Gastrointestinal disorders: Diarrhoea, Vomiting, Nausea
• Skin and subcutaneous tissue disorders: Dermatitis allergic
• Musculoskeletal, connective tissue and bone disorders: 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 providers are asked to report any suspected adverse reactions to SAHPRA on the SAHPRA website: u201c6.04 Adverse Drug Reactions Reporting Formu201d found online under SAHPRAu2019s publications: https//www.sahpra.org.za/Publications/Index/8.

Symptoms: Dizziness, headache, nausea and vomiting, diarrhoea. Faintness and hypotension may occur. Treatment would consist of enhancing diuresis (with fluids plus diuretics) and symptomatic treatment.