Actranex Film-Coated Tablet

Tranexamic acid tablets are an antifibrinolytic drug administered orally. The chemical name is trans-4-aminomethyl-cyclohexanecarboxylic acid.
Tranexamic acid is a white crystalline powder. It is freely soluble in water and in glacial acetic acid and is very slightly soluble in ethanol and practically insoluble in ether. The molecular formula is C₈H₁₅NO₂ and the molecular weight is 157.2.
Each film-coated tablet contains: Tranexamic Acid, BP 500 mg.

Antifibrinolytic.
Pharmacology: Pharmacodynamics: Tranexamic acid is an antifibrinolytic compound which is a potent competitive inhibitor of the activation of plasminogen to plasmin. It is a non-competitive plasmin inhibitor at much larger concentrations. Tranexamic acid inhibits plasminogen activation by urokinase 6-100 times more than aminocaproic acid, and streptokinase 6-40 times more than aminocaproic acid. Tranexamic acid has about ten times the antifibrinolytic action of aminocaproic acid.
Mechanism of action: Tranexamic acid is a synthetic derivative of the amino acid lysine and binds the 5 lysine binding sites on plasminogen. This inhibits plasmin formation and displaces plasminogen from the fibrin surface. It may also directly inhibit plasmin and partially inhibit fibrinogenolysis at higher concentrations. Tranexamic acid is also thought to exert an anti-inflammatory effect (by inhibiting plasmin-mediated activation of complement, monocytes, and neutrophils) and may improve platelet function in certain circumstances.
Pharmacokinetics: Absorption: Tranexamic acid is absorbed from the gastrointestinal tract. After oral administration of 1 or 2 g, the peak plasma concentrations are 8 or 15 mg/L, both obtained 3 hours after dosing. About 30 to 50% of the drug is bioavailable. Food intake does not influence absorption of the drug.
Distribution: Tranexamic acid has very low protein binding and widely distributed in the body, about 3% at therapeutic plasma concentrations and is accounted for by binding to plasminogen. It does not bind to serum albumin. The initial volume of distribution is 9 to 12 L. The active concentration of Tranexamic acid (antifibrinolytic) is 10 mcg/mL. When administered 36 to 48 hours before surgery in four doses of 10 to 20 mg/kg body weight, the drug remains in different tissues for about 17 hours and in serum up to 7 or 8 hours.
No data are available concerning the concentration in gastric juice, but the clinical effect of tranexamic acid on gastrointestinal bleeding has been demonstrated. Tranexamic acid crosses the placenta and passes into breastmilk.
Biotransformation: The possible routes of biotransformation are acetylation or deamination followed by oxidation or reduction. Approximately 50% of the parent compound, 2% of deaminated dicarboxylic acid and 0.5% of the acetylated product are excreted.
Excretion: Tranexamic acid is excreted in the urine by glomerular filtration mainly as unchanged drug. Less than 5% of metabolites are excreted in urine within 72 hours. After oral administration of a 10 to 15 mg/kg dose, the urinary excretion at 24 to 48 hours is 39% and 41%, respectively. The approximate plasma half-life of tranexamic acid is 2 hours.

Tranexamic acid is indicated for short term use for hemorrhage or risk of hemorrhage in those with increased fibrinolysis or fibrinogenolysis. Local fibrinolysis as occurs in the following conditions: Prostatectomy and bladder surgery; Menorrhagia; Epistaxis; Conization of the cervix; Traumatic hyphema; Patients with hemophilia undergoing dental extraction; Hereditary angioneurotic edema.

Adults: Local fibrinolysis: The recommended normal dosage is 15-25 mg/kg body weight (i.e., 2-3 tablets) two to three times daily. For the indications listed as follows, the following doses may be used: Prostatectomy: Prophylaxis and treatment of hemorrhage in high-risk patients should start pre- or post-operatively with the injectable form; followed by 2 tablets three to four times daily until macroscopic hematuria is no longer present.
Menorrhagia: Recommended dosage is 2 tablets 3 times daily as needed for up to 4 days. If there is very heavy menstrual bleeding, consider increasing the dosage. Maximum dose daily is 4 g (8 tablets). Until menstrual bleeding has started, treatment with Tranexamic acid should not be initiated.
Epistaxis: Where recurrent bleeding is anticipated, administer oral therapy (2 tablets three times daily) for 7 days.
Cervix conization: 3 tablets three times daily.
Traumatic hyphema: 2-3 tablets three times daily. The dose is based on 25 mg/kg three times a day.
Hemophilia: For dental extraction management, 2-3 tablets every eight hours. The dose is based on 25 mg/kg.
Hereditary angioneurotic edema: Awareness of the onset of illness are present in some of the patients; advisable treatment for these patients is intermittently 2-3 tablets two to three times daily for some days. Other patients are being treated at this dosage regularly.
Pediatric population: This should be calculated at 25 mg/kg per dose according to body weight. However, there are limited data on efficacy, posology, and safety for these indications.
Elderly: Unless there is evidence of renal failure, the reduction in dosage is unnecessary.
Renal insufficiency: Based on clearance data for the intravenous dosage form, the following oral dosage reduction is indicated for individuals with mild to severe renal insufficiency. (See Table 1.)

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Route of administration: Oral route.

Discontinue the treatment in case of overdose and seek medical attention immediately. There is no known antidote for Tranexamic acid overdose. Administration of activated charcoal within 1 or 2 hours after ingestion may help to decrease the absorption of Tranexamic acid. Activated charcoal may be administered via a nasogastric tube once the airway is protected in patients who are unconscious or have gag reflex. Monitor fluid and electrolyte levels in patients with severe vomiting or diarrhea. Administer intravenous fluids and replace electrolytes as necessary. Maintain high fluid intake to promote renal excretion. Monitor for clinical evidence of thromboembolic complications such as chest pain, shortness of breath, flank pain and extreme pain. There is a risk of thrombosis in predisposed individuals, anticoagulant therapy should be considered.

Tranexamic acid is contraindicated in patients with known hypersensitivity to the active substance, tranexamic acid, or any of its excipients.
Tranexamic acid is contraindicated in patients with the following conditions: 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.

In case of hematuria of renal origin (especially in hemophilia), there is a risk of mechanical anuria due to formation of a ureteral clot. Regular eye examinations (such as visual acuity, slit lamp, intraocular pressure, visual fields) and liver function tests should be performed in the long-term therapy of patients with hereditary angioneurotic edema.
Tranexamic acid should not be used by patients who have irregular menstrual bleeding until the source of the irregular bleeding has been determined. If Tranexamic acid does not adequately reduce monthly bleeding, an alternative treatment is recommended. Patients with thrombophilia who have had a past thromboembolic event and a family history of thromboembolic disease should use Tranexamic acid only if there is a substantial medical implication and under close medical supervision. Patients with renal impairment have elevated blood levels. As a result, a dose reduction is advised. Tranexamic acid should not be used in cases of enhanced fibrinolysis caused by disseminated intravascular coagulation. Treatment should be withdrawn from patients with visual disturbances.
Clinical experience with Tranexamic acid in menorrhagic children under 15 years of age is not available.
Potentially fatal: Because Tranexamic acid is antifibrinolytic, the risk of venous thromboembolism, as well as arterial thromboses such as stroke and myocardial infarction may increase further when combined hormonal contraceptives are administered with Tranexamic acid tablets. This is of particular concern in women who are obese or smoke cigarettes, especially smokers over 35 years of age.

Pregnancy: Pregnancy Category B.
There is no evidence of teratogenic effect from animal reproduction studies and there are no adequate and well-controlled studies in pregnant women. However, Tranexamic acid crosses the placenta and appears in cord blood. Tranexamic acid should only be used during pregnancy if considered essential.
Lactation: Tranexamic acid is present in the mother's milk at a concentration of about one hundredth of the corresponding serum concentration (Data: One hour after the last dose following a 2-day treatment course in lactating women, the milk concentration of the Tranexamic acid was 1% of the peak serum concentration).
There are no adequate data on the effects of Tranexamic acid on the breastfed infant or the effects of Tranexamic acid on milk production. Tranexamic acid should only be used during breastfeeding if considered essential.

Adverse effects have been ranked under headings of frequency using the following convention: See Table 2.

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The following undesirable effects have been reported: The most frequently reported adverse effects with Tranexamic acid include gastrointestinal disturbances (nausea, vomiting and diarrhea). These adverse effects may disappear when dose is reduced. The uncommon gastrointestinal disorders are abdominal pain, abdominal tenderness and discomfort, anorexia, bowel infarction, gastrointestinal discomfort and heartburn.
Immune system disorders: Very rare: Anaphylaxis and other hypersensitivity reactions.
Skin and subcutaneous tissue disorders: Rare: Allergic skin reactions.
Vascular disorders: Rare: Thromboembolic events.
Very rare: Arterial or venous thrombosis at any sites.
Eye disorders: Rare: Impaired color vision and other visual disturbances, retinal/artery occlusion.

Combined Hormonal Contraceptives: Concomitant use of combined hormonal contraception and Tranexamic acid may increase the thrombotic risk associated with combined hormonal contraceptives.
Tissue Plasminogen Activators: Concomitant therapy with tissue plasminogen activators may decrease the efficacy of both Tranexamic acid and tissue plasminogen activators. Discontinue Tranexamic acid tablets if a patient requires tissue plasminogen activators.
Factor IX Complex Concentrates or Anti-Inhibitor Coagulant Concentrates: Tranexamic acid tablets are not recommended in patients taking either Factor IX complex concentrates or anti-inhibitor coagulant concentrates because the risk of thrombosis may be increased.
All-Trans Retinoic Acid (Oral Tretinoin): Tranexamic acid tablets are not recommended in patients with acute promyelocytic leukemia taking all-trans retinoic acid for remission induction because of possible exacerbation of the procoagulant effect of all-trans retinoic acid.

Special Precautions for Handling and Disposal: No special instructions for handling and disposal of the drug product.

Store at temperatures not exceeding 30°C.
Do not store in direct sunlight or heat.
Shelf-life: 36 Months.

Haemostatics

B02AA02 - tranexamic acid ; Belongs to the class of amino acid antifibrinolytics. Used in the treatment of hemorrhage.

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