1. NAME OF THE MEDICINAL PRODUCT :
Savibleed 500 mg F. C. Tablets
2. QUALITATIVE AND QUANTITATIVE COMPOSITION :
Each film-coated tablet contains Tranexamic acid 500 mg as the active ingredient. For excipients, see 6.1
3. PHARMACEUTICAL FORM :
4. CLINICAL PARTICULARS :
4.1 Therapeutic indications
Tranexamic acid is an antifibrinolytic agent, which competitively inhibits the activation of plasminogen to plasmin.
Short-term use for haemorrhage or risk of haemorrhage in increased fibrinolysis or fibrinogenolysis.
Local fibrinolysis as occurs in the following conditions:
Prostatectomy and bladdersurgery
Conisation of the cervix
Hereditary angioneurotic oedema
Management of dental extraction in haemophiliacs
4.2 Posology and method of administration
Route of administration: Oral.
I-Local fibrinolysis: The recommended standard dosage is 15-25 mg/kg bodyweight (i.e. 2-3 tablets) two to three times daily. For the indications listed below the following doses may be used:
la. Prostatectomy: Prophylaxis and treatment of haemorrhage in high risk patients should commence per- or post-operatively with an SAVIBLEED Injection; thereafter 2 tablets three to four times daily until macroscopic haematuria is no longer present. lb. Menorrhagia: Recommended dosage is 2 tablets 3 times daily as long as needed for up to 4 days. If very heavy menstrual bleeding, dosage may be increased. A total dose of 4g daily (8 tablets) should not be exceeded. Treatment with 5AVIBLEED should not be initiated until menstrual bleeding has started.
le. Epistaxis: Where recurrent bleeding is anticipated oral therapy (2 tablets three times daily) should be administered for 7 days.
Id. Conisation of the cervix: 3 tablets three times daily.
le. Traumatic hyphaema: 2-3 tablets three times daily. The dose is based on 25 mg/kg
three times a day.
2. Haemophilia: In the management of dental extractions 2-3 tablets every ei ht hours.
The dose is based on 25 mg g.
3. Hereditary angioneurotic oedema: Some patients are aware of the onset of the illness; suitable treatment for these patients is intermittently 2-3 tablets two to three times daily for some days. Other patients are treated continuously at this dosage.
This should be calculated according to body weight at 25 mg/kg per dose.
No reduction in dosage is necessary unless there is evidence of renal failure (see guidelines below).
Renal insufficiency: By extrapolation from clearance data relating to the intravenous dosage form, the following reduction in the oral dosage is recommended for patients with mild to moderate renal insufficiency,
Serum creatinine (umol/i) Dose Tranexamic acid
120-249 15mg/kg body weight twice daily.
250-500 15 mg/kg body weight/day.
Hypersensitivity to tranexamic acid or any of the other ingredients,
Severe renal impairment because of risk of accumulation, Active thromboembolic disease. History of venous or arterial thrombosis
Fibrinolytic conditions following consumption coagulopathy
History of convulsions
4.4 Special warnings and precautions for use
In case of haematuria of renal origin (especially in haemophilia), there is a risk of mechani- cal anuria due to formation of a ureteral clot. In the long-term treatment of patients with hereditary angioneurotic oedema, regular eye examinations (e.g. visual acuity, slit lamp, intraocular pressure, visual fields) and liver function tests should be performed.
Patients with irregular menstrual bleeding should not use Tranexamic acid until the cause of irregular bleeding has been established. If menstrual bleeding is not adequately reduced by Tranexamic acid, an alternative treatment should be considered.
Patients with a previous thromboembolic event and a family history of thromboembolic disease (patients with thrombophilia) should use Tranexamic acid only if there is a strong medical indication and under strict medical supervision.
The blood levels are increased in patients with renal insufficiency. Therefore a dose reduction is recommended. The information on renal insufficiency is contained in section 4.2.
The use of tranexamic acid in cases of increased fibrinolysis due to disseminated intravascular coagulation is not recommended.
Patients who experience visual disturbance should be withdrawn frorn treatment.
Clinical experience with tranexamic acid in menorrhagic children under 15 years of age is not available.
4.5 Interaction with other medicinal products and other forms of interaction
SAVIBLEED will counteract the thrombolytic effect of fibrinolytic preparations.
4.6 Pregnancy and lactation
Although there is no evidence from animal studies of a teratogenic effect, the usual caution with the use of drugs in pregnancy should be observed. Tranexamic acid crosses the placenta.
Tranexamic acid passes into breast milk to a concentration of approximately one hundredth of the concentration in the maternal blood. An antifibrinolytic effect in the infant is unlikely.
4.7 Effects on ability to drive and use machines
4.8 Undesirable effects
Adverse events are listed below by system organ class and frequency. Frequencies are defined as: very common (;,1/10), common (;,1/100 and <1110), uncommon (;,111000
and <1/100), rare (;, 1110,000 and <111000) and very rare «1/10,000) including isolated
reports, not known (cannot be estimated from the available data).
Very rare: Hypersensitivity reactions including anaphylaxis
Rare: Colour vision disturbances, retinal/artery occlusion
Rare: Thromboembolic events
Very rare: Arterial or venous thrombosis at any sites Gastro-intestinal disorders
Very rare: Digestive effects such as nausea, vomiting and diarrhoea, may occur but disappear when the dosage is reduced. Skin and subcutaneous tissue disorders
Rare: Allergic skin reactions
Symptoms may be nausea, vomiting, orthostatic symptoms and/or hypotension. Initiate vomiting, then stomach lavage, and charcoal therapy. Maintain a high fluid intake to promote renal excretion. There is a risk of thrombosis in predisposed individuals.
Anticoagulant treatment should be considered.
5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Tranexamic acid is an antifibrinolytic compound which is a potent competitive inhibitor of the activation of plasminogen to plasmin. At much higher concentrations it is a non-competitive inhibitor of plasmin. The inhibitory effect of tranexamic acid in plasminogen activation by urokinase has been reported to be 6-100 times and by streptokinase 6-40 times greater than that of amiocaproic acid ; activity of tranexamic acid is approximately ten times greater than that of aminocaproic acid.
5.2 Pharmacokinetic properties
Peak plasma Tranexamic acid concentration is obtained immediately after intravenous administration (500 mg). Then concentration decreases until the 6th hour. Elimination half-life is about 3 hours.
Tranexamic acid administered parenterally is distributed in a two compartment model. Tranexamic acid is delivered in the cell compartment and the cerebrospinal fluid with delay. The distribution volume is about 33% of the body mass.
Tranexamic acid is excreted in urine as unchanged compound. 90% of the administered dose is excreted by the kidney in the twelve first hours after administration (glomerular excretion without tubular reabsorption). Following oral administration, 1.13% and 39% of the administered dose were recovered after 3 and 24 hours respectively. Tranexamic acid crosses the blood brain barrier.
Plasma concentrations are increased in patients with renal insufficiency.
6. PHARMACEUTICAL PARTICULARS :
6.1 List of excipients
Croscarmellose Sodium, Magnesium Stearate ,Hydroxypropyl cellulose 5 cps, Titanium Dioxide, PEG 6000, Talc, PVP 1<30, Aerosil 200, Povidone K30 , Pregelatinized Starch, Stearic acid.
6.2 Special precautions for storage
Store at temperature not exceeding 30°C in a dry place
6.3Nature and contents of container
Carton box containing 1,2 or 3 (AI Itransparent PVC! PVDC) strips each of 10 film coated tablets and insert leaflet
7-Savibleed Manufactured by :
Marcyrl Company for Pharmaceutical Industries
El obour City -Egypt