Mefatran

Uses

Mefenamic acid is used in mild to moderate pain including headache, dental pain, postoperative and postpartum pain, dysmenorrhoea, menorrhagia, in musculoskeletal and joint disorders such as osteoarthritis and rheumatoid arthritis; and in children with fever and juvenile idiopathic arthritis.

Haemorrhage or risk of haemorrhage in increased fibrinolysis or fibrinogenolysis that may occur in conditions:

• Prostatectomy and bladder surgery
• Menorrhagia
• Epistaxis
• Conisation of the cervix
• Management of dental extraction in patients with coagulopathies
• Ulcerative colitis
• Haematuria
• Gastrointestinal haemorrhage

General fibrinolysis as in prostatic and pancreatic cancer, after thoracic and other major surgery, in obstetrical complications such as abruptio placentae and post- partum haemorrhage, in leukaemia and liver diseases and in connection with thrombolytic therapy with streptokinase.

Hereditary angioneurotic oedema.

Mefatran is also used to associated treatment for these conditions: Mild pain, Primary Dysmenorrhoea, Gastrointestinal cramps, Moderate PainBleeding, Heavy Menstrual Bleeding, Hereditary Angioedema

How Mefatran works

Mefenamic acid binds the prostaglandin synthetase receptors COX-1 and COX-2, inhibiting the action of prostaglandin synthetase. As these receptors have a role as a major mediator of inflammation and/or a role for prostanoid signaling in activity-dependent plasticity, the symptoms of pain are temporarily reduced.

Tranexamic acid competitively and reversibly inhibits the activation of plasminogen via binding at several distinct sites, including four or five low-affinity sites and one high-affinity site, the latter of which is involved in its binding to fibrin. The binding of plasminogen to fibrin induces fibrinolysis - by occupying the necessary binding sites tranexamic acid prevents this dissolution of fibrin, thereby stabilizing the clot and preventing hemorrhage.

Dosage

Mefatran dosage

As with other NSAIDs, the lowest dose should be sought for each patient. Therefore, after observing the response to initial therapy with Mefenamic acid, the dose and frequency should be adjusted to suit an individual patient's needs.Administration is by the oral route, preferably with food.

• Adult: A 500 mg dose should be given to adults up to three times (1.5 g total) per day.
• Infants over 6 months: 25 mg/kg of body weight daily in divided doses for not longer than 7 days.

Intravenous administration is necessary only if it is difficult to give adequate doses by mouth. The recommended standard dose is 1 to 1.5 gm or 5-10 ml by slow intravenous injection at a rate of 1 ml/minute, two to three times daily. For the indications listed below the following doses are recommended.

PROSTATECTOMY: 5-10 ml by slow intravenous injection every eight hours (the first injection being given during the operation) for the first three days after surgery; thereafter 1-1.5 gm orally three to four times daily until macroscopic haematuria is no longer present.

MENORRHAGIA: 1-1.5 gm orally three to four times daily for three to four days.

EPISTAXIS: 1.5 gm orally three times daily for four to ten days.

Tranexamic Acid injection may be applied topically to the nasal mucosa of patients suffering from epistaxis. This can be done by soaking a gauze strip in the solution,and then packing the nasal cavity.

HAEMATURIA: 1-1.5 gm orally 2-3 times daily until macroscopic haematuria is no longer present.

CONISATION OF THE CERVIX: 1.5 gm orally 3 times a day for 12 to 14 days post-operatively.

DENTAL SURGERY IN PATIENTS WITH COAGULOPATHIES: Immediately before surgery, 10 mg per kg body-weight should be given intravenously. After surgery, 25 mg per kg body-weight are given orally three to four times daily for six to eight days. Coagulation factor concentrate might be necessary to administrate.

GENERAL FIBRINOLYSIS: 1 gm by slow intravenous injection three to four times daily. With fibrinolysis in conjunction with diagnosed, increased intravascular coagulation i.e. defibrillation syndrome, an anticoagulant such as heparin may be given with caution.

HEREDITARY ANGIONEUROTIC OEDEMA: 1-1.5 gm orally two to three times daily as intermittent or continuous treatment depending on whether the patient has prodromal symptoms or not.

CHILDREN:

• Oral dose: 25 mg/kg 2 to 3 times daily for 7 to 10 days.
• Injection: 10 mg/kg 6 to 8 hours for 7 to 10 days

Side Effects

In patients taking Mefenamic acid or other NSAIDs, the most frequently reported adverse experiences include : abdominal pain, constipation, diarrhoea, dyspepsia, flatulence, gross bleeding/perforation, heartburn, nausea, GI ulcers, vomiting, abnormal renal function, anaemia, dizziness, oedema, elevated liver enzymes, headache, increased bleeding time, pruritus, rash and tinnitus.

Dose-dependent, gastrointestinal discomfort is the most commonly reported undesirable effect, but it is usually of mild and temporary in nature. Allergic skin reactions have been reported as an uncommon undesirable effect. Hypotension may occur after fast injection.

Toxicity

Oral, rat LD₅₀: 740 mg/kg. Symptoms of overdose may include severe stomach pain, coffee ground-like vomit, dark stool, ringing in the ears, change in amount of urine, unusually fast or slow heartbeat, muscle weakness, slow or shallow breathing, confusion, severe headache or loss of consciousness.

Reported symptoms of tranexamic acid overdose include severe gastrointestinal symptoms, hypotension, thromboembolism, visual impairment, convulsions, mental status changes, and rash.

Precaution

NSAIDs should be prescribed with extreme caution in those with a prior history of ulcer disease or gastrointestinal bleeding. To minimise the potential risk for an adverse GI event, the lowest effective dose should be used for the shortest possible duration. In cases with pre-existing advanced kidney disease, treatment with Mefenamic acid is not recommended.

Patients with irregular menstrual bleeding, patients with a high risk of thrombosis (a previous thromboembolic event and a family history of thromboembolic disease) should use it only if there is a strong medical indication and under strict medical supervision.

Patients with disseminated intravascular coagulation (DIC), who require treatment with it must be under the strict supervision of a physician experienced in treating this disorder.

In the long-term treatment of patients, regular eye examination should be performed. If a colour vision disorder should occur during the course of treatment, the drug should be discontinued.

Interaction

Concomitant use with CYP2C9 isoenzyme inhibitors may alter safety and efficacy of mefenamic acid. May enhance methotrexate toxicity. Reduced BP response to ACE inhibitors or angiotensin II receptor antagonists. Increased risk of serious GI events with aspirin. May reduce the natriuretic effects of furosemide or thiazide diuretics. Reduced renal lithium clearance and elevated plasma lithium levels. May enhance anticoagulant effect of warfarin.

Clinically important interactions have not been observed with Tranexamic acid. Because of the absence of interaction studies, simultaneous treatment with anticoagulants must take place under the strict supervision of a physician experienced in this field.

Volume of Distribution

• 1.06 L/kg [Normal Healthy Adults (18-45 yr)]

The initial volume of distribution of tranexamic acid is 0.18 L/kg and its steady-state volume of distribution is 0.39 L/kg. Tranexamic acid distributes into cerebrospinal fluid and the aqueous humor of the eye at concentrations approximately 1/10th of typical plasma concentrations. Tranexamic acid is also able to cross the placenta, found in cord blood at concentrations equivalent to maternal plasma concentrations.

Elimination Route

Mefenamic acid is rapidly absorbed after oral administration.

The bioavailability of tranexamic acid after oral administration in humans is approximately 30 to 50% of the ingested dose and is not affected by food intake. The C_max and T_max following multiple oral doses (1300 mg three times daily x 5 days) were 16.41 mcg/mL and 2.5 h, respectively.

Half Life

2 hours

Following intravenous administration, the apparent elimination half-life is approximately 2 hours and the mean terminal half-life is approximately 11 hours.

Clearance

• Oral cl=21.23 L/hr [Healthy adults (18-45 yrs)]

The plasma clearance of tranexamic acid is 110-116 mL/min.

Elimination Route

The fecal route of elimination accounts for up to 20% of the dose, mainly in the form of unconjugated 3-carboxymefenamic acid.3 The elimination half-life of mefenamic acid is approximately two hours. Mefenamic acid, its metabolites and conjugates are primarily excreted by the kidneys. Both renal and hepatic excretion are significant pathways of elimination.

Urinary excretion is the primary means of tranexamic acid elimination, with >95% of an administered dose excreted in the urine as unchanged parent drug. The rate of excretion is dependent on the route of administration - approximately 90% of an intravenously administered dose is excreted within 24 hours whereas only 39% of an orally administered dose is excreted within the same time frame.

Pregnancy & Breastfeeding use

Pregnancy: In late pregnancy, as with other NSAIDs, Mefenamic acid should be avoided because it may cause premature closure of the ductus arteriosus. In general there are no adequate and well controlled studies in pregnant women. Mefenamic acid should be used during pregnancy only if the potential benefit justifies the potential risk to the foetus. Rated as Pregnancy Category C.

Lactation: Trace amounts of Mefenamic acid may be present in breast milk. Taking into account the importance of the drug to the mother , decision should be made whether to discontinue nursing or to discontinue the drug.

Pregnancy: Tranexamic acid crosses the placenta. Clinical experience of use in pregnant women is limited. Animal studies have not supplied any evidence of an increased incidence of fetal damage.

Lactation: Tranexamic acid is excreted into breast milk, but it is not likely to influence the child at therapeutic doses.

Contraindication

Mefenamic acid is contraindicated in patients with known hypersensitivity to Me Mefenamic acid acid. Mefenamic acid should not be given to patients who have experienced asthma, urticaria, or allergic type reactions after taking aspirin or other NSAIDs. Rarely fatal, anaphylactic like reactions to NSAIDs have been reported in such patients. Mefenamic acid is contraindicated in patients with active ulceration or chronic inflammation of upper gastrointestinal tract and should not be used in patients with preexisting renal disease.

• Active thromboembolic disease, such as deep vein thrombosis, pulmonary embolism and cerebral thrombosis
• Subarachnoid haemorrhage
• Hypersensitivity to Tranexamic acid or any of the ingredients

Special Warning

Renal Impairment:

Intravenous : Adjust dose based on the serum-creatinine concentration:

• 120-250 micromol/l: 10 mg/kg bid daily;
• 250-500 micromoles/l: 10 mg/kg once daily;
• >500 micromol/l: 5 mg/kg once daily or 10 mg/kg once every 48 hr.

Oral : Adjust dose based on serum creatinine concentration:

• 120-250 micromol/l: 15 mg/kg bid daily;
• 250-500 micromol/l: 15 mg/kg once daily;
• >500 micromol/l: 7.5 mg/kg once daily or 15 mg/kg once every 48 hr.

Pediatric Use: The drug has had limited use in pediatric patients, principally in connection with tooth extraction. The limited data suggest that dosing instructions for adults can be used for pediatric patients needing Tranexamic acid therapy.

Geriatric Use: Clinical studies of Tranexamic acid did not include sufficient numbers of subjects aged 65 and over to determine whether they respond different y from younger subjects. Other reported clinical experien e has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. Drug Interaction Tranexamic Acid is known to interact with other drugs like Factor VIII. These interactions are sometimes beneficial and sometimes may pose threats to life. Always consult your physician for the change of dose regimen or an alternative drug of choice that may strictly be required. Pharmaceutical Precaution Keep in a cool & dry place, protected from light. Keep out of the reach of children.

Acute Overdose

Symptoms: Headache, nausea, vomiting, epigastric pain, GI bleeding. Rarely, diarrhoea, disorientation, excitation, coma, drowsiness, tinnitus, fainting, and occasionally convulsions.

Management: Symptomatic and supportive treatment. In acute overdosage, empty the stomach immediately by inducing emesis or by gastric lavage followed by admin of activated charcoal.

Symptoms: Nausea, vomiting, dizziness, and headache.

Treatment of overdose: If justified, initiate vomiting, then gastric lavage, charcoal therapy, and symptomatic treatment. Maintain adequate diuresis.

Storage Condition

Store between 20-25° C.

Store at a cool and dry place, protected from light and moisture.

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