Tranamic Special Precautions

General: Dose should be reduced in patients with renal insufficiency because of risk of accumulation.
Ureteral obstruction due to clot formation in patients with upper respiratory tract bleeding has been reported.
Venous and arterial thrombosis or thromboembolism has been reported. In addition, cases of central retinal artery and central retinal vein obstruction have been reported.
Patients with previous history of thromboembolic disease may be at increased risk for venous or arterial thrombosis.
Tranexamic acid should not be administered concomitantly with Factor IX Complex concentrations or anti-inhibitor coagulant concentrates, as the risk of thrombosis may be increased.
Patients with disseminated intravascular coagulation, who require treatment with tranexamic acid, must be under strict supervision of a physician experienced in treating this disorder.
Carcinogenesis, mutagenesis, impairment of fertility: An increased incidence of leukemia in male mice receiving tranexamic acid in food at a concentration of 4.8% (equivalent to doses as high as 5 g/kg/day) may have been related to treatment. Female mice were not included in the experiment.
Hyperplasia of the biliary tract and cholangioma and adenocarcinoma of the intrahepatic biliary system have been reported in one strain of rats after dietary administration of doses exceeding the maximum tolerated dose for 22 months. Hyperplastic, but non neoplastic, lesions were reported at lower doses. Subsequently long term dietary administration studies in a different strain of rat, each with an exposure level equal to the maximum level employed in the earlier experiment, have failed to show such hyperplastic/neoplastic changes in the liver. No mutagenic activity has been demonstrated in several invitro and invitro test systems.
Mefenamic acid: General: Mefenamic acid cannot be expected to substitute for corticosteroids or to treat corticosteroid insufficiency. Abrupt discontinuation of corticosteroids may lead to disease exacerbation. Patients on prolonged corticosteroid therapy should have their therapy tapered slowly if a decision is made to discontinue corticosteroids.
Because mefenamic acid reduces inflammation, it may diminish the diagnostic signs for detecting complications of presumed non-infectious, painful conditions.
Hepatic Effects: Borderline elevations of one or more liver function tests may occur in up to 15% of patients taking NSAIDs, including mefenamic acid. In addition, rare cases of severe hepatic reactions, including jaundice and fatal fulminant hepatitis, liver necrosis and hepatic failure, some of them with fatal outcomes have been reported.
Renal Effects: Caution should be used when initiating treatment with mefenamic acid in patients with considerable dehydration. It is advisable to rehydrate patients first and then start therapy with mefenamic acid. Mefenamic acid is not recommended in patients with pre-existing kidney disease.
Long-term administration of mefenamic acid has resulted in renal papillary necrosis and other renal medullary changes. Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. Patients at greatest risk of this reaction are those with impaired renal function, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors and the elderly. Discontinuation of nonsteroidal anti-inflammatory drug therapy is usually followed by recovery to the pretreatment state.
Mefenamic acid metabolites are eliminated primarily by the kidneys. The extent to which the metabolites may accumulate in patients with renal failure has not been studied.
Hematological Effects: Anemia is sometimes seen in patients receiving NSAIDs, including mefenamic acid. This may be due to fluid retention, GI loss or an effect upon erythropoiesis. Patients on long-term treatment with NSAIDs, including mefenamic acid, should have their hemoglobin or hematocrit checked if they exhibit any signs or symptoms of anemia.
All drugs, which inhibit the biosynthesis of prostaglandins, may interfere to some extent with platelet function and vascular response to bleeding.
NSAIDs inhibit platelet aggregation and have been shown to prolong bleeding time in some patients. Unlike aspirin, their effect on platelet function is quantitatively less or shorter duration and reversible. Mefenamic acid dose not generally affect platelet count or partial thromboplastin time (PTT), but may prolong prothrombin time (PT). Patients receiving mefenamic acid who may be adversely affected by alterations in platelet function, such as those with coagulation disorders or patients receiving anticoagulants, should be careful monitored.
Fluid Retention and Edema: Fluid retention and edema have been observed in some patients taking NSAIDs.
Pre-existing Asthma: Patients with asthma may have aspirin-sensitive asthma. Since cross-reactivity, including bronchospasm, between aspirin and other nonsteroidal anti-inflammatory drugs have been reported in such aspirin-sensitive patients, mefenamic acid should not be administered to patients with this form of aspirin sensitivity and should be used with caution in patients with pre-existing asthma.
Laboratory Tests: Patients on long-term treatment with NSAIDs should have their CBC and a chemistry profile checked periodically. If clinical signs and symptoms consistent with liver or renal disease develop, systemic manifestations occur (e.g. eosinophilia, rash, etc.) or if abnormal liver test persist or worsen, Tranexamic Acid and Mefenamic Acid should be discontinued.
Use in Pregnancy: Pregnancy (Category B): Reproduction studies performed in mice, rats and rabbits have not revealed any evidence of impaired fertility or adverse effects on the fetus due to tranexamic acid. There are no adequate and well-controlled studies in pregnant women. However, tranexamic acid is known to pass the placenta and appears in cord blood at concentrations approximately equal to maternal concentration. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
Use in Lactation: Tranexamic acid is present in the mother’s milk at a concentration of about a hundredth of the corresponding serum levels. Caution should be exercised when tranexamic acid is administered to a nursing woman.
Use in Children: Drug has limited use in pediatric patients. Limited data suggest that dosing instructions for adults can be used in pediatric patients.
Mefenamic acid: Safety and effectiveness in pediatric patients below the age of 14 have not been established.
Use in the Elderly: 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.
Mefenamic acid: As with any NSAID, caution should be exercised in treating the elderly (65 years and older).