Precautions and Contraindications
Patients should be advised that mefenamic acid, like other NSAIAs, is not free of potential adverse effects, including some that can cause discomfort, and that more serious effects (e.g., myocardial infarction, stroke, GI bleeding), which may require hospitalization and may even be fatal, also can occur. Patients also should be informed that, while NSAIAs may be commonly employed for conditions that are less serious, NSAIA therapy often is considered essential for the management of some diseases, and the drugs have a major role in the management of pain. Clinicians may wish to discuss with their patients the potential risks and likely benefits of NSAIA therapy, particularly when consideration is being given to use of these drugs in less serious conditions for which therapy without an NSAIA may represent an acceptable alternative to both the patient and clinician.
Patients should be advised to read the medication guide for NSAIAs that is provided to the patient each time the drug is dispensed.
NSAIAs increase the risk of serious adverse cardiovascular thrombotic events.(See Cautions: Cardiovascular Effects.) To minimize the potential risk of adverse cardiovascular events, the lowest effective dosage and shortest possible duration of therapy should be employed. Some clinicians suggest that it may be prudent to avoid use of NSAIAs whenever possible in patients with cardiovascular disease. Patients receiving NSAIAs (including those without previous symptoms of cardiovascular disease) should be monitored for the possible development of cardiovascular events throughout therapy. Patients should be informed about the signs and symptoms of serious cardiovascular toxicity (chest pain, dyspnea, weakness, slurring of speech) and instructed to seek immediate medical attention if such toxicity occurs. Mefenamic acid should be avoided in patients with recent myocardial infarction unless the benefits of therapy are expected to outweigh the risk of recurrent cardiovascular thrombotic events; if mefenamic acid is used in such patients, the patient should be monitored for cardiac ischemia.
There is no consistent evidence that concomitant use of low-dose aspirin mitigates the increased risk of serious cardiovascular events associated with NSAIAs. Concomitant use of aspirin and an NSAIA increases the risk for serious GI events. Because of the potential for increased adverse effects, patients receiving mefenamic acid should be advised not to take aspirin.
Use of NSAIAs can result in the onset of hypertension or worsening of preexisting hypertension; either of these occurrences may contribute to the increased incidence of cardiovascular events. Patients receiving NSAIAs may have an impaired response to diuretics (i.e., thiazide or loop diuretics), angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists, or β-adrenergic blocking agents. NSAIAs should be used with caution in patients with hypertension. Blood pressure should be monitored closely during initiation of NSAIA therapy and throughout therapy.
Because NSAIAs increase morbidity and mortality in patients with heart failure, the manufacturer states that mefenamic acid should be avoided in patients with severe heart failure unless the benefits of therapy are expected to outweigh the risk of worsening heart failure; if mefenamic acid is used in such patients, the patient should be monitored for worsening heart failure. Some experts state that use of NSAIAs should be avoided whenever possible in patients with reduced ventricular ejection fraction and current or prior symptoms of heart failure. Patients receiving NSAIAs should be advised to inform their clinician if they experience symptoms of heart failure, including dyspnea, unexplained weight gain, and edema. Use of NSAIAs may diminish the cardiovascular effects of certain drugs used to treat heart failure and edema (e.g., diuretics, ACE inhibitors, angiotensin II receptor antagonists).(See Drug Interactions.)
The risk of potentially serious adverse GI effects should be considered in patients receiving mefenamic acid, particularly in patients receiving chronic therapy with the drug.(See Cautions: GI Effects.) Mefenamic acid should be used with caution in patients with a history of upper GI disease. Since peptic ulceration and/or GI bleeding have been reported in patients receiving the drug, patients should be advised to promptly report signs or symptoms of GI ulceration or bleeding to their clinician.
Mefenamic acid should be used with extreme caution and under close supervision in patients with a history of GI bleeding or peptic ulceration, and such patients should receive an appropriate ulcer preventive regimen. All patients considered at increased risk of potentially serious adverse GI effects (e.g., geriatric patients, those receiving high therapeutic dosages of NSAIAs, those with a history of peptic ulcer disease, those receiving anticoagulants or corticosteroids concomitantly) should be monitored closely for signs and symptoms of ulcer perforation or GI bleeding. To minimize the potential risk of adverse GI effects, the lowest effective dosage and shortest possible duration of therapy should be employed. For patients who are at high risk, therapy other than an NSAIA should be considered. The manufacturer states that mefenamic acid is contraindicated in patients with active ulceration or chronic inflammation of the upper or lower GI tract.
The possibility that the antipyretic and anti-inflammatory effects of NSAIAs may mask the usual signs and symptoms of infection or other diseases should be considered.
Elevations in serum ALT may be the most sensitive indicator of NSAIA-induced liver dysfunction. Patients who experience signs and/or symptoms suggestive of liver dysfunction or an abnormal liver function test result while receiving mefenamic acid should be evaluated for evidence of the development of a severe hepatic reaction. Severe reactions, including jaundice and fatal fulminant hepatitis, liver necrosis, and hepatic failure (sometimes fatal), have been reported in patients receiving NSAIAs. Although such reactions are rare, mefenamic acid should be discontinued if abnormal liver function test results persist or worsen, if clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g., eosinophilia, rash).
Patients receiving mefenamic acid are at risk of developing adverse renal effects. Renal toxicity has been observed in patients in whom renal prostaglandins have a compensatory role in maintaining renal perfusion. Administration of an NSAIA to such patients may cause a dose-dependent reduction in prostaglandin formation and thereby precipitate overt renal decompensation. Patients at greatest risk of this reaction include those with impaired renal function, heart failure, or hepatic dysfunction; those with extracellular fluid depletion (e.g., patients receiving diuretics); those taking an ACE inhibitor or angiotensin II receptor antagonist concomitantly; and geriatric patients. Patients should be advised to consult their clinician promptly if unexplained weight gain or edema occurs. Recovery of renal function to pretreatment levels usually occurs following discontinuance of NSAIA therapy.
The manufacturer states that mefenamic acid should not be administered to patients with substantial renal impairment.
Mefenamic acid is not a substitute for corticosteroid therapy. Use of corticosteroids during NSAIA therapy may increase the risk of GI ulceration, and the drugs should be used concomitantly with caution. If corticosteroid dosage is decreased during mefenamic acid therapy, it should be done gradually and patients should be observed for adverse effects, including adrenocortical insufficiency or symptomatic exacerbation of the inflammatory condition being treated.
Mefenamic acid should be used with caution in patients who may be adversely affected by a prolongation of bleeding time (e.g., patients receiving anticoagulant therapy), because the drug may inhibit platelet function. If signs and/or symptoms of anemia occur during therapy with mefenamic acid, hemoglobin concentration and hematocrit should be determined.
Anaphylactoid reactions have been reported in patients receiving mefenamic acid. Patients receiving mefenamic acid should be informed of the signs and symptoms of an anaphylactoid reaction (e.g., difficulty breathing, swelling of the face or throat) and advised to seek immediate medical attention if an anaphylactoid reaction develops.
Serious skin reactions (e.g., exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis) can occur in patients receiving NSAIAs. These serious skin reactions may occur without warning; patients should be advised to consult their clinician if skin rash and blisters, fever, or other signs of hypersensitivity reaction (e.g., pruritus) occur. Mefenamic acid should be discontinued at the first appearance of rash or any other sign of hypersensitivity.
Patients receiving long-term NSAIA therapy should have a complete blood cell count and chemistry profile performed periodically.
The manufacturers state that mefenamic acid is contraindicated in patients with known hypersensitivity to the drug. In addition, NSAIAs generally are contraindicated in patients in whom asthma, urticaria, or other sensitivity reactions are precipitated by aspirin or other NSAIAs, since there is potential for cross-sensitivity between NSAIAs and aspirin, and severe, often fatal, anaphylactic reactions may occur in such patients. Although NSAIAs generally are contraindicated in these patients, the drugs have occasionally been used in NSAIA-sensitive patients who have undergone desensitization. Because patients with asthma may have aspirin-sensitivity asthma, NSAIAs should be used with caution in patients with asthma. In patients with asthma, aspirin sensitivity is manifested principally as bronchospasm and usually is associated with nasal polyps; the association of aspirin sensitivity, asthma, and nasal polyps is known as the aspirin triad. For a further discussion of cross-sensitivity of NSAIAs,
NSAIAs are contraindicated in the setting of CABG surgery.