Mefenamic Acid Information
Mefenamic acid (Mefenamic) Description
Mefenamic acid (Mefenamic) is a member of the fenamate group of nonsteroidal anti-inflammatory drugs (NSAIDs). Each Size ‘1‘ Yellow-Yellow capsule, with ‘PAD‘ imprinted on the cap & ‘195‘ imprinted on the body, contains 250 mg of Mefenamic acid (Mefenamic) for oral administration. Mefenamic acid (Mefenamic) is a white to greyish-white, odorless, microcrystalline powder with a melting point of 230°-231°C and water solubility of 0.004% at pH 7.1. The chemical name is N-2,3-xylylanthranilic acid. The molecular weight is 241.29. Its molecular formula is CHN0 and the structural formula of Mefenamic acid (Mefenamic) is:
Each capsule also contains lactose monohydrate. The capsule shell contains D&C yellow No. 10; FD&C blue No. 1; FD&C red No. 3; FD&C yellow No. 6; gelatin, sodium lauryl sulfate, titanium dioxide, black iron oxide, propylene glycol & shellac.
Mefenamic acid (Mefenamic) Clinical Pharmacology
Absorption:
1,2
Following a single 1 gram oral dose, mean peak plasma levels ranging from 10-20 mcg/mL have been reported. Peak plasma levels are attained in 2 to 4 hours and the elimination half-life approximates 2 hours. Following multiple doses, plasma levels are proportional to dose with no evidence of drug accumulation. In a multiple dose trial of normal adult subjects (n=6) receiving 1 gram doses of Mefenamic acid (Mefenamic) four times daily, steady-state concentrations of 20 mcg/mL were reached on the second day of administration, consistent with the short half-life.
The effect of food on the rate and extent of absorption of Mefenamic acid (Mefenamic) has not been studied.
Concomitant ingestion of antacids containing magnesium hydroxide has been shown to significantly increase the rate and extent of Mefenamic acid (Mefenamic) absorption (see ).
Distribution:
Based on its physical and chemical properties, Mefenamic acid (Mefenamic) is expected to be excreted in human breast milk.
Metabolism:
Excretion:
3
The elimination half-life of Mefenamic acid (Mefenamic) is approximately two hours. Half-lives of metabolites I and II have not been precisely reported, but appear to be longer than the parent compound. The metabolites may accumulate in patients with renal or hepatic failure. The Mefenamic acid (Mefenamic) glucuronide may bind irreversibly to plasma proteins. Because both renal and hepatic excretions are significant pathways of elimination, dosage adjustments in patients with renal or hepatic dysfunction may be necessary. Mefenamic acid (Mefenamic) should not be administered to patients with preexisting renal disease or in patients with significantly impaired renal function.
Pediatric:
11
Race:
Hepatic Insufficiency:
Renal Insufficiency:
Mefenamic acid (Mefenamic) Indications And Usage
Carefully consider the potential benefits and risks of Mefenamic acid (Mefenamic) and other treatment options before deciding to use Mefenamic acid (Mefenamic) . Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see ).
Mefenamic acid (Mefenamic) is indicated:
Mefenamic acid (Mefenamic) Contraindications
Mefenamic acid (Mefenamic) is contraindicated in patients with known hypersensitivity to Mefenamic acid (Mefenamic) .
Mefenamic acid (Mefenamic) should not be given to patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. Severe, rarely fatal, anaphylactic-like reactions to NSAIDs have been reported in such patients (see and ).
Mefenamic acid (Mefenamic) is contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery (see ).
Mefenamic acid (Mefenamic) is contraindicated in patients with acute active ulceration or chronic inflammation of either the upper or lower gastrointestinal tract.
Mefenamic acid (Mefenamic) should not be used in patients with preexisting renal disease.
Mefenamic acid (Mefenamic) Warnings Cardiovascular Effects
Clinical trials of several Cox-2 selective and nonselective NSAIDs of up to three years duration have shown an increased risk of serious cardiovascular (CV) thrombotic events, myocardial infarction, and stroke, which can be fatal. All NSAIDs, both COX-2 selective and nonselective, may have a similar risk. Patients with known CV disease or risk factors for CV disease may be at greater risk. To minimize the potential risk for an adverse CV event in patients treated with an NSAID, the lowest effective dose should be used for the shortest duration possible. Physicians and patients should remain alert for the development of such events, even in the absence of previous CV symptoms. Patients should be informed about the signs and/or symptoms of serious CV events and the steps to take if they occur.
There is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious CV thrombotic events associated with NSAID use. The concurrent use of aspirin and an NSAID does increase the risk of serious GI events (see ).
Two large, controlled, clinical trials of a COX-2 selective NSAID for the treatment of pain in the first 10-14 days following CABG surgery found an increased incidence of myocardial infarction and stroke (see ).
NSAIDs, including Mefenamic acid (Mefenamic) , can cause serious gastrointestinal (GI) adverse events including inflammation, bleeding, ulceration, and perforation of the stomach, small intestine, or large intestine, which can be fatal. These serious adverse events can occur at any time, with or without warning symptoms, in patients treated with NSAIDs. Only one in five patients, who develop a serious upper GI adverse event on NSAID therapy, is symptomatic. Upper GI ulcers, gross bleeding, or perforation caused by NSAIDs occur in approximately 1% of patients treated for 3-6 months, and in about 2-4% of patients treated for one year. These trends continue with longer duration of use, increasing the likelihood of developing a serious GI event at some time during the course of therapy. However, even short-term therapy is not without risk.
NSAIDs should be prescribed with extreme caution in those with a prior history of ulcer disease or gastrointestinal bleeding. Patients with a who use NSAIDs have a greater than 10-fold increased risk for developing a GI bleed compared to patients with neither of these risk factors. Other factors that increase the risk for GI bleeding in patients treated with NSAIDs include concomitant use of oral corticosteroids or anticoagulants, longer duration of NSAID therapy, smoking, use of alcohol, older age, and poor general health status. Most spontaneous reports of fatal GI events are in elderly or debilitated patients and therefore, special care should be taken in treating this population.
To minimize the potential risk for an adverse GI event in patients treated with an NSAID, the lowest effective dose should be used for the shortest possible duration. Patients and physicians should remain alert for signs and symptoms of GI ulceration and bleeding during NSAID therapy and promptly initiate additional evaluation and treatment if a serious GI adverse event is suspected. This should include discontinuation of the NSAID until a serious GI adverse event is ruled out. For high risk patients, alternate therapies that do not involve NSAIDs should be considered.
Mefenamic acid (Mefenamic) Precautions
Mefenamic acid (Mefenamic) 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.
The pharmacological activity of Mefenamic acid (Mefenamic) in reducing fever and inflammation may diminish the utility of these diagnostic signs in detecting complications of presumed noninfectious, painful conditions.
Borderline elevations of one or more liver tests may occur in up to 15% of patients taking NSAIDs including Mefenamic acid (Mefenamic) . These laboratory abnormalities may progress, may remain unchanged, or may be transient with continuing therapy. Notable elevations of ALT and AST (approximately three or more times the upper limit of normal) have been reported in approximately 1% of patients in clinical trials with NSAIDs. 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.
A patient with symptoms and/or signs suggesting liver dysfunction, or in whom an abnormal liver test has occurred, should be evaluated for evidence of the development of a more severe hepatic reaction while on therapy with Mefenamic acid (Mefenamic) . If clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g., eosinophilia, rash, etc.), Mefenamic acid (Mefenamic) should be discontinued.
Patients should be informed of the following information before initiating therapy with an NSAID and periodically during the course of ongoing therapy. Patients should also be encouraged to read the NSAID Medication Guide that accompanies each prescription dispensed.
A number of compounds are inhibitors of CYP2C9. Drug interactions studies of Mefenamic acid (Mefenamic) and these compounds have not been conducted. The possibility of altered safety and efficacy should be considered when Mefenamic acid (Mefenamic) is used concomitantly with these drugs.
ACE-inhibitors
Reports suggest that NSAIDs may diminish the antihypertensive effect of ACE inhibitors. This interaction should be given consideration in patients taking NSAIDs concomitantly with ACE-inhibitors.
Aspirin
When Mefenamic acid (Mefenamic) is administered with aspirin, its protein binding is reduced, although the clearance of free Mefenamic acid (Mefenamic) is not altered. The clinical significance of this interaction is not known; however, as with other NSAIDs, concomitant administration of Mefenamic acid (Mefenamic) and aspirin is not generally recommended because of the potential of increased adverse effects.
Diuretics
Clinical studies, as well as postmarketing observations, have shown that Mefenamic acid (Mefenamic) can reduce the natriuretic effect of furosemide and thiazides in some patients. This response has been attributed to inhibition of renal prostaglandin synthesis. During concomitant therapy of NSAIDs, the patient should be observed closely for signs of renal failure (see ), as well as to assure diuretic efficacy.
Lithium
NSAIDs have produced an elevation of plasma lithium levels and a reduction in renal lithium clearance. The mean minimum lithium concentration increased 15% and the renal clearance decreased by approximately 20%. These effects have been attributed to inhibition of renal prostaglandin synthesis by the NSAID. Thus, when NSAIDs and lithium are administered concurrently, subjects should be observed carefully for signs of lithium toxicity.
Methotrexate
NSAIDs have been reported to competitively inhibit methotrexate accumulation in rabbit kidney slices. This may indicate that they could enhance the toxicity of methotrexate. Caution should be used when NSAIDs are administered concomitantly with methotrexate.
Warfarin
The effects of warfarin and NSAIDs on GI bleeding are synergistic, such that users of both drugs together have a risk of serious GI bleeding higher than users of either drug alone.
Antacids
In a single dose study (n=6), ingestion of an antacid containing 1.7 grams of magnesium hydroxide with 500 mg of Mefenamic acid (Mefenamic) increased the C and AUC of Mefenamic acid (Mefenamic) by 125% and 36%, respectively.
Clinical studies of Mefenamic acid (Mefenamic) did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. As with any NSAIDs, caution should be exercised in treating the elderly (65 years or older).
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 (see and ).
Mefenamic acid (Mefenamic) Adverse Reactions
In patients taking Mefenamic acid (Mefenamic) or other NSAIDs, the most frequently reported adverse experiences occurring in approximately 1-10% of patients are:
Gastrointestinal experiences including - abdominal pain, constipation, diarrhea, dyspepsia, flatulence, gross bleeding/perforation, heartburn, nausea, GI ulcers (gastric/duodenal), vomiting, abnormal renal function, anemia, dizziness, edema, elevated liver enzymes, headaches, increased bleeding time, pruritus, rashes, tinnitus Additional adverse experiences reported occasionally and listed here by body system include: Body as a whole - fever, infection, sepsis
Cardiovascular system - congestive heart failure, hypertension, tachycardia, syncope.
Digestive system - dry mouth, esophagitis, gastric/peptic ulcers, gastritis, gastrointestinal bleeding, glossitis, hematemesis, hepatitis, jaundice.
Hemic and lymphatic system - ecchymosis, eosinophilia, leukopenia, melena, purpura, rectal bleeding, stomatitis, thrombocytopenia.
Metabolic and nutritional - weight changes.
Nervous system - anxiety, asthenia, confusion, depression, dream abnormalities, drowsiness; insomnia, malaise, nervousness, paresthesia, somnolence, tremors, vertigo.
Respiratory system - asthma, dyspnea.
Skin and appendages - alopecia, photosensitivity, pruritus, sweat.
Special senses - blurred vision.
Urogenital system - cystitis, dysuria, hematuria, interstitial nephritis, oliguria/polyuria, proteinuria, renal failure
Other adverse reactions, which occur rarely are:
Body as a whole - anaphylactoid reactions, appetite changes, death.
Cardiovascular system - arrhythmia, hypotension, myocardial infarction, palpitations, vasculitis
Digestive system - eructation, liver failure, pancreatitis.
Hemic and lymphatic system - agranulocytosis, hemolytic anemia, aplastic anemia, lymphadenopathy, pancytopenia.
Metabolic and nutritional – hyperglycemia.
Nervous system - convulsions, coma, hallucinations, meningitis.
Respiratory - respiratory depression, pneumonia.
Skin and appendages - angioedema, toxic epidermal necrosis, erythema multiforme exfoliative dermatitis, Stevens-Johnson syndrome, urticaria.
Special senses - conjunctivitis, hearing impairment
Mefenamic acid (Mefenamic) Overdosage
Symptoms following acute NSAIDs overdoses are usually limited to lethargy, drowsiness, nausea, vomiting, and epigastric pain, which are generally reversible with supportive care. Gastrointestinal bleeding can occur. Hypertension, acute renal failure, respiratory depression and coma may occur, but are rare. Anaphylactoid reactions have been reported with therapeutic ingestion of NSAIDs, and may occur following an overdose.
Patients should be managed by symptomatic and supportive care following an NSAID overdose. There are no specific antidotes. Emesis and/or activated charcoal (60 to 100 g in adults, 1 to 2 g/kg in children) and/or osmotic cathartic may be indicated in patients seen within 4 hours of ingestion with symptoms or following a large overdose (5 to 10 times the usual dose). Forced diuresis, alkalinization of urine, hemodialysis, or hemoperfusion may not be useful due to high protein binding.
Mefenamic acid (Mefenamic) Dosage And Administration
Carefully consider the potential benefits and risks of Mefenamic acid (Mefenamic) and other treatment options before deciding to use Mefenamic acid (Mefenamic) . Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see ).
After observing the response to initial therapy with Mefenamic acid (Mefenamic) , the dose and frequency should be adjusted to suit an individual patient's needs.
For the relief of acute pain in adults and adolescents ≥ 14 years of age, the recommended dose is 500 mg as an initial dose followed by 250 mg every 6 hours as needed, usually not to exceed one week.
For the treatment of primary dysmenorrhea, the recommended dose is 500 mg as an initial dose followed by 250 mg every 6 hours, given orally, starting with the onset of bleeding and associated symptoms. Clinical studies indicate that effective treatment can be initiated with the start of menses and should not be necessary for more than 2 to 3 days.
Mefenamic acid (Mefenamic) How Supplied
Mefenamic acid (Mefenamic) Capsules USP 250 mg are Size ‘1’ yellow-yellow capsules with ‘PAD’ imprinted on the cap & ‘195’ imprinted on the body. They are supplied as follows:
Bottles of 30 NDC 0574-0195-30
Bottles of 100 NDC 0574-0195-01
Storage
Store at 20-25°C (68-77°F); excursions permitted to 15-30°C (59-86°F) [See USP Controlled Room Temperature].
Mefenamic acid (Mefenamic) References
Manufactured in India by: MICRO LABS LIMITED Plot No. S-155-159, Verna Industrial Estate Phase-III, Verna GOA 403722, INDIA.
Mefenamic acid (Mefenamic) Medication Guide For Non-steroidal Anti-inflammatory Drugs (nsaids)
NSAID medicines may increase the chance of a heart attack or stroke that can lead to death.
The chance of a person getting an ulcer or bleeding increases with:
NSAID medicines should only be used:
Do not take an NSAID medicine:
Tell your healthcare provider:
Serious side effects include:
Other side effects include:
Get emergency help right away if you have any of the following symptoms:
Stop your NSAID medicine and call your healthcare provider right away if you have any of the following symptoms:
These are not all the side effects with NSAID medicines. Talk to your healthcare provider or pharmacist for more information about NSAID medicines.
*
This medication guide has been approved by the U.S. Food and Drug Administration.
Manufactured in India by: MICRO LABS LIMITED Plot No. S-155-159, Verna Industrial Estate Phase-III, Verna GOA 403722, INDIA.
Paddock Laboratories, Inc.
Mefenamic acid (Mefenamic) Package Label Principal Display Panel
NDC 0574-0195-01
100 CAPSULES
