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Mefenamic Acid

Pronunciation

Pronunciation: MEF-e-NAM-ik AS-id
Class: NSAID

Trade Names

Ponstel
- Capsules, oral 250 mg

Apo-Mefenamic (Canada)

Pharmacology

Decreases inflammation, pain, and fever, probably through inhibition of cyclooxygenase activity and prostaglandin synthesis.

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Pharmacokinetics

Absorption

Rapidly absorbed. T max is 2 to 4 h. C max is 20 mcg/mL (single doses). Steady state is reached in 2 days.

Distribution

Apparent Vd is 1.06 L/kg. Protein binding is more than 90%. Excreted in breast milk.

Metabolism

Metabolized by CYP-450 enzyme CYP2C9 to 3-hydroxymethyl mefenamic acid (metabolite I). Further oxidation to a 3-carboxymefenamic acid (metabolite II) may occur. The metabolites may undergo glucuronidation, and mefenamic acid is also glucuronidated directly.

Elimination

Approximately 52% of a 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. The half-life is approximately 2 h.

Special Populations

Renal Function Impairment

The potential exists for mefenamic acid metabolites to accumulate.

Hepatic Function Impairment

The potential exists for mefenamic acid metabolites to accumulate.

Children

Mefenamic acid has not been adequately investigated in pediatric patients younger than 14 y. A study in 17 preterm infants administered 2 mg/kg indicated that the half-life was approximately 5 times as long as adults; the mean C max was 4 mcg/mL (range, 2.9 to 6.1) and T max was 8 h (range, 2 to 18 h).

Race

Pharmacokinetic differences because of race have not been identified.

Indications and Usage

For relief of mild to moderate pain in patients 14 y and older; treatment of primary dysmenorrhea.

Unlabeled Uses

Migraine (including acute attack and menstrual); PMS.

Contraindications

Hypersensitivity to mefenamic acid; patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs; treatment of perioperative pain in the setting of coronary artery bypass graft (CABG) surgery; active ulceration or chronic inflammation of either the upper or lower GI tract; preexisting renal disease.

Dosage and Administration

Mild to Moderate Pain
Adults and Children (14 y and older)

PO 500 mg, followed by 250 mg every 6 h as needed for up to 7 days.

Primary Dysmenorrhea
Adults and Children (14 y and older)

PO 500 mg starting with onset of bleeding and associated symptoms followed by 250 mg every 6 h for 2 to 3 days after the start of menses.

Hepatic Function Impairment

PO May require reduced doses.

Storage/Stability

Store between 59° and 86°F.

Drug Interactions

ACE inhibitors (eg, enalapril)

The antihypertensive effects of ACE inhibitors may be diminished. Also, the risk of nephrotoxicity associated with ACE inhibitors or mefenamic acid may be increased. Closely monitor BP.

Alcohol

The risk of GI bleeding may be increased.

Aminoglycosides (eg, tobramycin)

The risk of acute renal failure may be increased. Avoid coadministration.

Antacids containing magnesium hydroxide

Antacids containing magnesium hydroxide increase the rate and extent of mefenamic acid absorption.

Anticoagulants

Increased risk of gastric erosion and bleeding. Use with caution and close monitoring.

Bisphosphonates (eg, alendronate)

Synergistic action may increase the risk of GI adverse reactions (eg, gastric ulceration). Use with caution. Closely monitor for GI adverse reactions.

Clopidogrel, corticosteroids (eg, prednisone), dabigatran, desirudin

The risk of bleeding may be increased. Use with caution.

Cyclosporine, tacrolimus

The risk of nephrotoxicity may be increased. Closely monitor renal function and cyclosporine and tacrolimus concentrations. If an interaction is suspected, decrease the cyclosporine and tacrolimus dose or discontinue mefenamic acid.

CYP2C9 inhibitors (eg, disulfiram, modafinil)

Exercise caution when coadministering mefenamic acid with drugs known to inhibit the CYP2C9 isoenzyme.

Heparin and factor Xa inhibitors (eg, enoxaparin)

The risk of bleeding may be increased. Avoid coadministration.

Lithium

Serum lithium levels may be increased. Closely monitor for signs of lithium toxicity.

Loop diuretic (eg, furosemide), thiazide diuretics (eg, chlorothiazide)

NSAIDs can reduce the natriuretic effect of loop and thiazide diuretics in some patients. Closely monitor patients for signs of renal failure.

Methotrexate

Increased methotrexate levels, increasing the risk of methotrexate toxicity (eg, bone marrow suppression, nephrotoxicity, mucositis). Fatal toxicity has occurred. Avoid concurrent use of high doses of methotrexate with mefenamic acid.

Pemetrexed

Plasma concentrations and toxic effects of pemetrexed may be increased. A 2- to 5-day suspension of mefenamic acid before and 2 days after pemetrexed administration may be warranted. Alternatively, ibuprofen may be an acceptable alternative to mefenamic acid in patients with healthy renal function who are receiving pemetrexed.

Probenecid

Pharmacologic and toxic effects of mefenamic acid may be increased. Clinical monitoring for signs of NSAID-related toxicity is warranted.

Quinolones (eg, norfloxacin)

Risk of CNS stimulation and seizures from quinolones may be increased. In addition, plasma concentrations of quinolones may be increased. Coadminister with caution.

Rivaroxaban

The risk of bleeding may be increased. Coadminister with caution. Close clinical monitoring is warranted.

Salicylates

Additive GI toxicity. Coadministration is not recommended.

Serotonin reuptake inhibitors (eg, fluoxetine, venlafaxine)

The risk of upper GI bleeding may be increased. Avoid coadministration. Use of acid suppression therapy may be considered.

Smoking

The risk of GI bleeding may be increased.

Triamterene

The risk of acute renal failure may be increased. Avoid coadministration.

Laboratory Test Interactions

May cause prolonged bleeding time or false-positive reaction for urinary bile using the diazo tablet test.

Adverse Reactions

Cardiovascular

CHF; hypertension; syncope; tachycardia.

CNS

Dizziness, headache (up to 10%).

Dermatologic

Pruritus, rashes (up to 10%).

GI

Abdominal pain, constipation, diarrhea, dyspepsia, flatulence, GI ulcers (gastric/duodenal), gross bleeding/perforation, heartburn, nausea, vomiting (up to 10%).

Hematologic

Anemia, increased bleeding time (up to 10%).

Hepatic

Elevated liver enzymes (up to 10%).

Miscellaneous

Abnormal renal function, edema, tinnitus (up to 10%).

Precautions

Warnings

CV risk

NSAIDs may cause an increased risk of serious CV thrombotic events, MI, and stroke, which can be fatal. This risk may increase with duration of use. Patients with CV disease or risk factors for CV disease may be at greater risk. Mefenamic acid is contraindicated for treatment of perioperative pain in the setting of CABG surgery.

GI risk

NSAIDs cause an increased risk of serious GI adverse events, including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients are at greater risk of serious GI events.


Monitor

Closely monitor BP during initiation and throughout the course of treatment. Monitor for signs and symptoms of GI bleeding. Patients on long-term treatment should have their CBC and a chemistry profile checked periodically. Carefully monitor patients receiving mefenamic acid who may be adversely affected by alterations in platelet function, such as those with coagulation disorders or patients receiving anticoagulants. If clinical signs and symptoms consistent with liver or renal disease develop, systemic manifestations occur (eg, eosinophilia, rash), or abnormal LFTs persist or worsen, discontinue mefenamic acid.


Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and effectiveness have not been established in pediatric patients younger than 14 y.

Elderly

Increased risk of adverse reactions. Use with caution.

Hypersensitivity

Anaphylactoid reactions may occur. Mefenamic acid should not be given to patients with the aspirin triad.

Renal Function

Not recommended for use in patients with preexisting renal disease or in patients with significantly impaired renal function.

Special Risk Patients

Use extreme caution in patients with a history of ulcer disease or GI bleeding.

Asthma

Mefenamic acid should not be administered to patients with aspirin-sensitive asthma and should be used with caution in patients with preexisting asthma.

Congestive heart failure/Edema

Fluid retention and edema have been reported. Use with caution in patients with fluid retention or heart failure.

Dermatologic effects

Serious skin adverse events, such as exfoliative dermatitis, Stevens-Johnson syndrome, and TEN, may occur, and can be fatal.

Hematologic effects

Anemia is sometimes seen in patients receiving NSAIDs, including mefenamic acid. NSAIDs inhibit platelet aggregation and have been shown to prolong bleeding time in some patients.

Hepatic effects

Borderline elevations of 1 or more LFTs may occur. 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.

Hypertension

New or worsening hypertension may occur. Use with caution in patients with hypertension.

Infection

The pharmacological activity of mefenamic acid in reducing fever and inflammation may diminish the utility of these diagnostic signs in detecting complications of presumed noninfectious, painful conditions.

Renal effects

Long-term NSAID use has resulted in renal papillary necrosis and other renal injury. Patients at greatest risk of this reaction include those with impaired renal function, heart failure, liver dysfunction, those taking diuretics or ACE inhibitors, and elderly patients.

Overdosage

Symptoms

Acute renal failure, anaphylactoid reactions, coma, drowsiness, epigastric pain, GI bleeding, hypertension, lethargy, nausea, respiratory depression, vomiting.

Patient Information

  • Advise patients to read the Medication Guide before starting therapy and with each refill.
  • Advise patients that mefenamic acid, like other NSAIDs, may cause serious CV effects, such as MI or stroke, which may result in hospitalization and even death. Although serious CV events can occur without warning symptoms, instruct patients to be alert for the signs and symptoms of chest pain, shortness of breath, weakness, and slurring of speech, and instruct patients to ask for medical advice when observing any indicative signs or symptoms.
  • Advise patients that mefenamic acid, like other NSAIDs, can cause GI discomfort and, rarely, serious GI adverse effects, such as ulcers and bleeding, which may result in hospitalization and even death. Although serious GI tract ulcerations and bleeding can occur without warning symptoms, instruct patients to be alert for the signs and symptoms of ulcerations and bleeding, and instruct patients to ask for medical advice when observing any indicative signs or symptoms, including epigastric pain, dyspepsia, melena, and hematemesis.
  • Advise patients that mefenamic acid, like other NSAIDs, can cause serious skin adverse reactions, such as exfoliative dermatitis, Stevens-Johnson syndrome, and TEN, which may result in hospitalizations and even death. Although serious skin reactions may occur without warning, inform patients to be alert for the signs and symptoms of skin rash and blisters, fever, or other signs of hypersensitivity, such as itching, and instruct patients to ask for medical advice when observing any indicative signs or symptoms. Advise patients to stop the drug immediately if they develop any type of rash and to contact their health care provider as soon as possible.
  • Instruct patients to promptly report signs or symptoms of unexplained weight gain or edema to their health care provider.
  • Inform patients of the warning signs and symptoms of hepatotoxicity (eg, nausea, fatigue, lethargy, pruritus, jaundice, right upper quadrant tenderness, “flu-like” symptoms). If these occur, instruct patients to stop taking mefenamic acid and seek immediate medical therapy.
  • Inform patients of the signs of an anaphylactoid reaction (eg, difficulty breathing, swelling of the face or throat). If these occur, instruct patients to seek immediate emergency help.
  • Inform patients to avoid mefenamic acid in late pregnancy because it may cause premature closure of the ductus arteriosus.

Copyright © 2009 Wolters Kluwer Health.

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