Ponstel® (mefenamic acid) is a member of the fenamate group of nonsteroidal anti-inflammatory drugs (NSAIDs). Each blue-banded, ivory capsule contains 250 mg of mefenamic acid for oral administration. Mefenamic acid 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 2-{(2,3-dimethylphenyl) amino-N-2,3-xylylanthranilic acid. The molecular weight is 241.29. Its molecular formula is C 15 H 15 NO 2 and the structural formula of mefenamic acid is:

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Each capsule also contains lactose, NF. The capsule shell and/or band contains citric acid, USP; D&C yellow No. 10; FD&C blue No. 1; FD&C red No. 3; FD&C yellow No. 6; gelatin, NF; glycerol monooleate; silicon dioxide, NF; sodium benzoate, NF; sodium lauryl sulfate, NF; titanium dioxide, USP.

Pharmacodynamics

Ponstel is a nonsteroidal anti-inflammatory drug (NSAID) that exhibits anti-inflammatory, analgesic, and antipyretic activities in animal models. The mechanism of action of Ponstel, like that of other NSAIDs, is not completely understood but may be related to prostaglandin synthetase inhibition.

Absorption:   Mefenamic acid is rapidly absorbed after oral administration. In two 500-mg single oral dose studies, the mean extent of absorption was 30.5 mcg/hr/mL (17%CV). 1,2 The bioavailability of the capsule relative to an IV dose or an oral solution has not been studied.

Following a single 1-gram oral dose, mean peak plasma levels ranging from 10-20 mcg/mL 3 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 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 has not been studied. Concomitant ingestion of antacids containing magnesium hydroxide has been shown to significantly increase the rate and extent of mefenamic acid absorption (see PRECAUTIONS , Drug Interactions ). 1

Distribution   Mefenamic acid has been reported as being greater than 90% bound to albumin. 9 The relationship of unbound fraction to drug concentration has not been studied. The apparent volume of distribution (Vz ss /F) estimated following a 500-mg oral dose of mefenamic acid was 1.06 L/kg. 2

Based on its physical and chemical properties, Ponstel is expected to be excreted in human breast milk.

Metabolism:   Mefenamic acid is metabolized by cytochrome P450 enzyme CYP2C9 to 3-hydroxymethyl mefenamic acid (Metabolite I). Further oxidation to a 3-carboxymefenamic acid (Metabolite II) may occur. 10 The activity of these metabolites has not been studied. The metabolites may undergo glucuronidation and mefenamic acid is also glucuronidated directly. A peak plasma level approximating 20 mcg/mL was observed at 3 hours for the hydroxy metabolite and its glucuronide (n=6) after a single 1-gram dose. Similarly, a peak plasma level of 8 mcg/mL was observed at 6-8 hours for the carboxy metabolite and its glucuronide. 3

Excretion   Approximately fifty-two percent of a mefenamic acid dose is excreted into the urine primarily as glucuronides of mefenamic acid (6%), 3-hydroxymefenamic acid (25%) and 3-carboxymefenamic acid (21%). 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. Half-lives of metabolites I and II have not been precisely reported, but appear to be longer than the parent compound. 3 The metabolites may accumulate in patients with renal or hepatic failure. The mefenamic acid glucuronide may bind irreversibly to plasma proteins. Because both renal and hepatic excretion are significant pathways of elimination, dosage adjustments in patients with renal or hepatic dysfunction may be necessary. Ponstel should not be administered to patients with preexisting renal disease or in patients with significantly impaired renal function.

TABLE 1. Pharmacokinetic Parameter Estimates for
Mefenamic Acid
PK Parameters
Normal Healthy Adults (18-45 yr)
 
Value CV
Tmax(hr)
2 66
Oral clearance (L/hr)
21.23 38
Apparent volume of distribution; Vz/F (L/kg)
1.06 60
Half-life; t 1 / 2 (hrs)
2 to 4 NA

Special Populations

Pediatric   Ponstel has not been adequately investigated in pediatric patients less than 14 years of age. A study in 17 preterm infants administered 2 mg/kg indicated that the half-life was about five times as long as adults, consistent with the low activity of metabolic enzymes in newborn infants. The mean Cmax in this study was 4 mcg/mL (range 2.9-6.1). The mean time to maximum concentration (Tmax) was 8 hours (range 2-18 hrs). 11

Race:   Pharmacokinetic differences due to race have not been identified.

Hepatic Insufficiency:   Mefenamic acid pharmacokinetics have not been studied in patients with hepatic dysfunction. As hepatic metabolism is a significant pathway of mefenamic acid elimination, patients with acute and chronic hepatic disease may require reduced doses of Ponstel compared to patients with normal hepatic function.

Renal Insufficiency:   Mefenamic acid pharmacokinetics have not been investigated in subjects with renal insufficiency. Given that mefenamic acid, its metabolites and conjugates are primarily excreted by the kidneys, the potential exists for mefenamic acid metabolites to accumulate. Ponstel should not be administered to patients with preexisting renal disease or in patients with significantly impaired renal function.

Clinical Studies

In controlled, double-blind, clinical trials, Ponstel was evaluated for the treatment of primary spasmodic dysmenorrhea. The parameters used in determining efficacy included pain assessment by both patient and investigator; the need for concurrent analgesic medication; and evaluation of change in frequency and severity of symptoms characteristic of spasmodic dysmenorrhea. Patients received either Ponstel, 500 mg (2 capsules) as an initial dose of 250 mg every 6 hours, or placebo at onset of bleeding or of pain, whichever began first. After three menstrual cycles, patients were crossed over to the alternate treatment for an additional three cycles. Ponstel was significantly superior to placebo in all parameters, and both treatments (drug and placebo) were equally tolerated.

Ponstel is indicated:

CONTRAINDICATIONS

Ponstel is contraindicated in patients with known hypersensitivity to mefenamic acid. Ponstel 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 -- Anaphylactoid Reactions , and PRECAUTIONS -- Preexisting Asthma ).

Ponstel is contraindicated in patients with active ulceration or chronic inflammation of either the upper or lower gastrointestinal tract.

Ponstel should not be used in patients with preexisting renal disease.

Gastrointestinal (GI) Effects--Risk of GI Ulceration, Bleeding, and Perforation

Serious gastrointestinal toxicity, such as inflammation, bleeding, ulceration, and perforation of the stomach, small intestine or large intestine, can occur at any time, with or without warning symptoms, in patients treated with non-steroidal anti-inflammatory drugs (NSAIDs). Minor upper gastrointestinal problems, such as dyspepsia, are common and may also occur at any time during NSAID therapy. Therefore, physicians and patients should remain alert for ulceration and bleeding, even in the absence of previous GI tract symptoms. Patients should be informed about the signs and/or symptoms of serious GI toxicity and the steps to take if they occur. The utility of periodic laboratory monitoring has not been demonstrated, nor has it been adequately assessed. Only one in five patients, who develop a serious upper GI adverse event on NSAID therapy, is symptomatic. It has been demonstrated that upper GI ulcers, gross bleeding or perforation, caused by NSAIDs, appear to 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, thus 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. 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, the lowest effective dose should be used for the shortest possible duration. For high risk patients, alternate therapies that do not involve NSAIDs should be considered.

Studies have shown that patients with a prior history of peptic ulcer disease and/or gastrointestinal bleeding and who use NSAIDs, have a greater than 10-fold risk for developing a GI bleed than patients with neither of these risk factors. In addition to a past history of ulcer disease, pharmacoepidemiological studies have identified several other cotherapies or comorbid conditions that may increase the risk for GI bleeding such as: treatment with oral corticosteroids, treatment with anticoagulants, longer duration of NSAID therapy, smoking, alcoholism, older age, and poor general health status.

Anaphylactoid Reactions

As with other NSAIDs, anaphylactoid reactions may occur in patients without known prior exposure to Ponstel. Ponstel should not be given to patients with the aspirin triad. This symptom complex typically occurs in asthmatic patients who experience rhinitis with or without nasal polyps, or who exhibit severe, potentially fatal bronchospasm after taking aspirin or other NSAIDs (see CONTRAINDICATIONS and PRECAUTIONS -- Preexisting Asthma ). Emergency help should be sought in cases where an anaphylactoid reaction occurs.

Advanced Renal Disease

In cases with preexisting advanced kidney disease, treatment with Ponstel is not recommended (see CONTRAINDICATIONS ).

Pregnancy

In late pregnancy, as with other NSAIDs, Ponstel should be avoided because it may cause premature closure of the ductus arteriosus.

PRECAUTIONS

General

Ponstel 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 Ponstel reduces inflammation, it may diminish the diagnostic signs for detecting complications of presumed noninfectious, painful conditions.

Hepatic Effects

Borderline elevations of one or more liver function tests may occur in up to 15% of patients taking NSAIDs, including Ponstel. These laboratory abnormalities may progress, may remain unchanged, or may be transient with continuing therapy. Notable elevations of ALT or 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 Ponstel. If clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (eg, eosinophilia, rash, etc.), Ponstel should be discontinued.

Renal Effects

Caution should be used when initiating treatment with Ponstel in patients with considerable dehydration. It is advisable to rehydrate patients first and then start therapy with Ponstel. Ponstel is not recommended in patients with pre-existing kidney disease (see CONTRAINDICATIONS ).

Long-term administration of Ponstel has resulted in renal papillary necrosis and other renal medullary changes. Renal toxicity has also been seen in patients in which renal prostaglandins have a compensatory role in the maintenance of renal perfusion. In these patients, administration of a nonsteroidal anti-inflammatory drug may cause a dose-dependant reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation. 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.

Ponstel 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 Ponstel. This may be due to fluid retention, GI loss, or an effect upon erythropoiesis. Patients on long-term treatment with NSAIDs, including Ponstel, 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 responses 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. Ponstel does not generally affect platelet counts, or partial thromboplastin time (PTT), but may prolong prothrombin time (PT). Patients receiving Ponstel who may be adversely affected by alterations in platelet function, such as those with coagulation disorders or patients receiving anticoagulants, should be carefully monitored.

Fluid Retention and Edema

Fluid retention and edema have been observed in some patients taking NSAIDs. Therefore, as with other NSAIDs, Ponstel should be used with caution in patients with fluid retention, hypertension, or heart failure.

Preexisting Asthma

Patients with asthma may have aspirin-sensitive asthma. The use of aspirin in patients with aspirin-sensitive asthma has been associated with severe bronchospasm which can be fatal. Since cross reactivity, including bronchospasm, between aspirin and other nonsteroidal anti-inflammatory drugs has been reported in such aspirin-sensitive patients, Ponstel should not be administered to patients with this form of aspirin sensitivity and should be used with caution in patients with preexisting asthma.

Information for Patients

Ponstel, like other drugs of its class, can cause discomfort and, rarely, more serious side effects, such as gastrointestinal bleeding, which may result in hospitalization and even fatal outcomes. Although serious GI tract ulcerations and bleeding can occur without warning symptoms, patients should be alert for the signs and symptoms of ulcerations and bleeding, and should ask for medical advice when observing any indicative sign or symptoms. Patients should be apprised of the importance of this follow-up (see WARNING , Risk of Gastrointestinal Ulceration, Bleeding and Perforation ).

Patients should report to their physicians signs or symptoms of gastrointestinal ulceration or bleeding, skin rash, weight gain, or edema.

Patients should be informed of the warning signs and symptoms of hepatotoxicity (eg, nausea, fatigue, lethargy, pruritus, jaundice, right upper quadrant tenderness, and "flu-like" symptoms). If these occur, patients should be instructed to stop therapy and seek immediate medical therapy.

Patients should also be instructed to seek immediate emergency help in the case of an anaphylactoid reaction (see ).

In late pregnancy, as with other NSAIDs, Ponstel should be avoided because it may cause premature closure of the ductus arteriosus.

NSAIDs are often essential agents in the management of arthritis and have a major role in the treatment of pain, but they also may be commonly employed for conditions which are less serious.

Physicians may wish to discuss with their patients the potential risks (see , PRECAUTIONS , and ADVERSE REACTIONS sections) and likely benefits of NSAID treatment, particularly when the drugs are used for less serious conditions where treatment without NSAIDs may represent an acceptable alternative to both the patient and physician.

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 (eg, eosinophilia, rash, etc.) or if abnormal liver tests persist or worsen, Ponstel should be discontinued.

Drug Interactions

Aspirin   As with other NSAIDs, concomitant administration of Ponstel and aspirin is not generally recommended because of the potential of increased adverse effects.

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.

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.

Furosemide   Clinical studies, as well as post-marketing observations, have shown that NSAIDs 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 Ponstel with furosemide, the patient should be observed closely for signs of renal failure (see PRECAUTIONS , Renal Effects ), 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 was 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.

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-gram of magnesium hydroxide with 500-mg of mefenamic acid increased the Cmax and AUC of mefenamic acid by 125% and 36%, respectively. 1

A number of compounds are inhibitors of CYP2C9 including fluconazole, lovastatin and trimethoprim. Drug interaction studies of mefenamic acid of these compounds have not been conducted. The possibility of altered safety and efficacy should be considered when Ponstel is used concomitantly with these drugs.

Drug/Laboratory Test Interactions

Ponstel may prolong prothrombin time. 4 Therefore, when the drug is administered to patients receiving oral anticoagulant drugs, frequent monitoring of prothrombin time is necessary.

A false-positive reaction for urinary bile, using the diazo tablet test, may result after mefenamic acid administration. If biliuria is suspected, other diagnostic procedures, such as the Harrison spot test, should be performed.

Pregnancy

Teratogenic Effects:    Pregnancy Category C. Reproduction studies have been performed in rats, rabbits, and dogs. Rats given up to 10 times the human dose showed decreased fertility, delay in parturition, and a decreased rate of survival to weaning. Rabbits at 2.5 times the human dose showed an increase in the number of resorptions. There were no fetal anomalies observed in these studies nor in dogs at up to 10 times the human dose. 4

However, animal reproduction studies are not always predictive of human response. There are no adequate and well-controlled studies in pregnant women. Ponstel should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nonteratogenic Effects:   Because of the known effects of nonsteroidal anti-inflammatory drugs on the fetal cardiovascular system (closure of ductus arteriosus), use during pregnancy (particularly late pregnancy) should be avoided.

Labor and Delivery

In rat studies with NSAIDs, as with other drugs known to inhibit prostaglandin synthesis, an increased incidence of dystocia, delayed parturition, and decreased pup survival occurred. The effects of Ponstel on labor and delivery in pregnant women are unknown.

Nursing Mothers

Trace amounts of Ponstel may be present in breast milk and transmitted to the nursing infant. 7 Because of the potential for serious adverse reactions in nursing infants from Ponstel, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

Safety and effectiveness in pediatric patients below the age of 14 have not been established.

Geriatric Use

As with any NSAID, caution should be exercised in treating the elderly (65 years and older).

ADVERSE REACTIONS

In patients taking Ponstel 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

Nervious 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--anphylactoid 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

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 a 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.

DOSAGE AND ADMINISTRATION

As with other NSAIDs, the lowest dose should be sought for each patient. Therefore, after observing the response to initial therapy with Ponstel, the dose and frequency should be adjusted to suit an individual patient' needs.

Administration is by the oral route, preferably with food.

For 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. 4

For the treatment of primary dysmenorrhea, the recommended dose is 500 mg as an initial dose followed by 250 mg every 6 hours, 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. 5

HOW SUPPLIED

Ponstel (mefenamic acid) is available as 250 mg blue-banded, ivory capsules, imprinted with "FHPC 400."

Bottles of 100 N 59630-0400-10

Storage

Store at controlled room temperature 15°-30°C (59°-86°F). Protect from moisture.

REFERENCES

  1. Neuvonen PJ, Kivisto KT: Enhancement of drug absorption by antacids. An unrecognized drug interation. Clin Pharmacokinet. 27: 120-8, Aug 1994.
  2. Tall AR, Mistilits SP: Studies on Ponstan (mefenamic acid): I. Gastro-intestinal blood loss; II. Absorption and excretion of a new formulation. J Int Med Res (UK). 1975, 3 (3) p176-82.
  3. Winder CV, Kaump DH, Glazko et al: Experimental observations of flufenamic, mefenamic, and meclofenamic acids. AnnPhys Med (Eng), Suppl p7-49. 1967.
  4. Glazko AJ: Experimental observations of flufenamic, mefenamic, and meclofenamic acids. Part III. Metabolic disposition, in Fenamates in Medicine. A Symposium, London, 1966. Annals of Physical Medicine, Supplement, pp 23-36, 1967.
  5. Data on file, Medical Affairs Dept, Parke-Davis.
  6. Budoff PW: Use of mefenamic acid in the treatment of primary dysmenorrhea. JAMA. 241:2713-2716, 1979.
  7. Buchanan RA, et al. The breast milk excretion of mefenamic acid. Curr Ther Res. 10:592, 1968.
  8. Corby DG, Decker WJ: Management of acute poisioning with activated charcoal. Pediatrics. 54:324, 1974.
  9. Champion GD, Graham GG: of non-steroidal anti-inflammatory agents. Aust NZ J Med. 8 (Supp 1): 94-100, Jun 1978.
  10. McGurk KA, Remmel RP, Hosagrahara VP, Tosh D, Burchell B: Reactivity of mefenamic acid 1-o- acyl glucuronide with proteins in vitro and ex vivo. Drug Metab Dispos. Aug 1996, 24 (8) p842-9.
  11. Ito K, Niida Y, Sato J et al: of mefenamic acid in preterm infants with patent ductus arteriosus. Acta Paediatr JPN. 36 (4): 387-91, 1994.

Rx only

Revised May 2000

© 1996-'00, FHPC

Manufactured by

PARKE-DAVIS

Div or Warner-Lambert Co

Morris Plains, NJ 07950 USA

Distributed by

First Horizon Pharmaceutical Corporation

Roswell, GA 30076