Ponstel

Generic Name: Mefenamic Acid
Class: Other Nonsteroidal Anti-inflammatory Agents
VA Class: MS120
Chemical Name: N-(2,3-xylyl)anthranilic acid
Molecular Formula: C15H15NO2
CAS Number: 61-68-7

Warning(s)

  • Cardiovascular Risk
  • Possible increased risk of serious (sometimes fatal) cardiovascular thrombotic events (e.g., MI, stroke).125 b Risk may increase with duration of use.125 b Individuals with cardiovascular disease or risk factors for cardiovascular disease may be at increased risk.125 b (See Cardiovascular Effects under Cautions.)

  • Contraindicated for the treatment of pain in the setting of CABG surgery.125 b

  • GI Risk
  • Increased risk of serious (sometimes fatal) GI events (e.g., bleeding, ulceration, perforation of the stomach or intestine).100 104 125 b Serious GI events can occur at any time and may not be preceded by warning signs and symptoms.100 101 104 125 b Geriatric individuals are at greater risk for serious GI events.125 b (See GI Effects under Cautions.)

Introduction

Prototypical NSAIA; anthranilic acid derivative (fenamate); structurally and pharmacologically related to meclofenamate sodium.125 a

Uses for Ponstel

Consider potential benefits and risks of mefenamic acid therapy as well as alternative therapies before initiating therapy with the drug.125 b Use lowest possible effective dosage and shortest duration of therapy consistent with patient’s treatment goals.125 b

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Pain

Relief of mild to moderate pain in patients ≥14 years of age when the duration of therapy ≤1 week.125 b

Dysmenorrhea

Treatment of primary dysmenorrhea.125 b

Fever

Has been used for reduction of fever associated with infection in children; routine use as an antipyretic not recommended because of potential adverse effects.a

Ponstel Dosage and Administration

General

  • Consider potential benefits and risks of mefenamic acid therapy as well as alternative therapies before initiating therapy with the drug.125 b

Administration

Oral Administration

Administer orally.125 May be administered in divided doses up to 4 times daily.125

Dosage

To minimize the potential risk of adverse cardiovascular and/or GI events, use lowest effective dosage and shortest duration of therapy consistent with the patient’s treatment goals.125 b Adjust dosage based on individual requirements and response; attempt to titrate to the lowest effective dosage.125 b

Pediatric Patients

Pain
Oral

Adolescents ≥14 years of age should receive dosage recommended for adults.125 (See Adult Dosage.)

Adults

Pain
Oral

For mild to moderate pain in adults, 500 mg initially followed by 250 mg every 6 hours as necessary.125

Dysmenorrhea
Oral

For relief of primary dysmenorrhea in adults, 500 mg initially followed by 250 mg every 6 hours as necessary.125 Initiate at onset of bleeding and associated symptoms; treatment should not be necessary for >2–3 days.125

Prescribing Limits

Pediatric Patients

Pain
Oral

Duration of therapy usually should not exceed 1 week.125

Adults

Pain
Oral

Duration of therapy usually should not exceed 1 week.125

Dysmenorrhea
Oral

Therapy should not be necessary for more than 2–3 days.125

Special Populations

Hepatic Impairment

Dosage reduction may be required.125

Renal Impairment

Dosage reduction may be required if used in patients with renal impairment.125

Use not recommended in patients with preexisting renal disease or substantial renal impairment.125

Geriatric Patients

Select dosage carefully since may be more likely to have decreased renal function.125 b

Cautions for Ponstel

Contraindications

  • Known hypersensitivity to mefenamic acid or any ingredient in the formulation.125 b

  • History of asthma, urticaria, or other sensitivity reaction precipitated by aspirin or other NSAIAs.125 b

  • Treatment of perioperative pain in the setting of CABG surgery.125 b

  • Active ulceration or chronic inflammation of upper or lower GI tract.125

  • Preexisting renal disease.125

Warnings/Precautions

Warnings

Cardiovascular Effects

Selective COX-2 inhibitors have been associated with increased risk of cardiovascular events (e.g., MI, stroke) in certain situations.125 129 Several prototypical NSAIAs also have been associated with increased risk of cardiovascular events.125 133 134 135 Information not available on risk associated with mefenamic acid at this time.133 134 135 136

Use NSAIAs with caution and careful monitoring (e.g., monitor for development of cardiovascular events) and at the lowest effective dosage for the shortest duration necessary.125 b

Short-term use to relieve acute pain, especially at low dosages, does not appear to be associated with increased risk of serious cardiovascular events (except immediately following CABG surgery).125 b

No consistent evidence that concomitant use of low-dose aspirin mitigates the increased risk of serious adverse cardiovascular events associated with NSAIAs.125 b (See Specific Drugs under Interactions.)

Hypertension and worsening of preexisting hypertension reported; either event may contribute to the increased incidence of cardiovascular events.125 b Use with caution in patients with hypertension; monitor BP.125 b Impaired response to certain diuretics may occur.125 b (See Specific Drugs under Interactions.)

Fluid retention and edema reported.125 b Caution in patients with fluid retention or heart failure.125 b

GI Effects

Serious GI toxicity (e.g., bleeding, ulceration, perforation) can occur with or without warning symptoms; increased risk in those with a history of GI bleeding or ulceration, geriatric patients, smokers, those with alcohol dependence, and those in poor general health.100 104 124 125 126 b

For patients at high risk for complications from NSAIA-induced GI ulceration (e.g., bleeding, perforation), consider concomitant use of misoprostol;124 127 h i alternatively, consider concomitant use of a proton-pump inhibitor (e.g., omeprazole)124 h i or use of an NSAIA that is a selective inhibitor of COX-2 (e.g., celecoxib).125 h

Renal Effects

Direct renal injury, including renal papillary necrosis, reported in patients receiving long-term NSAIA therapy.125 b

Potential for overt renal decompensation.125 b Increased risk of renal toxicity in patients with renal or hepatic impairment or heart failure, in geriatric patients, in patients with volume depletion, and in those receiving a diuretic, ACE inhibitor, or angiotensin II receptor antagonist.125 128 b (See Renal Impairment under Cautions.)

Sensitivity Reactions

Hypersensitivity Reactions

Anaphylactoid reactions reported.125 b

Immediate medical intervention and discontinuance for anaphylaxis.125 b

Avoid in patients with aspirin triad (aspirin sensitivity, asthma, nasal polyps); caution in patients with asthma.125 b

Dermatologic Reactions

Serious skin reactions (e.g., exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis) reported; can occur without warning.125 b Discontinue at first appearance of rash or any other signs of hypersensitivity (e.g., blisters, fever, pruritus).125 b

General Precautions

Hepatic Effects

Severe reactions including jaundice, fatal fulminant hepatitis, liver necrosis, and hepatic failure (sometimes fatal) reported rarely with NSAIAs.125 b

Elevations of serum ALT or AST reported.125 b

Monitor for symptoms and/or signs suggesting liver dysfunction; monitor abnormal liver function test results.125 b Discontinue if signs or symptoms of liver disease or systemic manifestations (e.g., eosinophilia, rash) occur.125 b

Hematologic Effects

Anemia reported rarely.125 b Determine hemoglobin concentration or hematocrit in patients receiving long-term therapy if signs or symptoms of anemia occur.125 b

May inhibit platelet aggregation and prolong bleeding time.125 b

Ocular Effects

Visual disturbances reported; ophthalmic evaluation recommended if visual changes occur.125 a

Other Precautions

Not a substitute for corticosteroid therapy; not effective in the management of adrenal insufficiency.125 b

May mask certain signs of infection.125 b

Obtain CBC and chemistry profile periodically during long-term use.125 b

Specific Populations

Pregnancy

Category C.125 b Avoid use in third trimester because of possible premature closure of the ductus arteriosus.125 b

Lactation

Distributed into milk.125 c Discontinue nursing or the drug.125

Pediatric Use

Safety and efficacy not established in children <14 years of age.125

Geriatric Use

Use with caution in patients ≥65 years of age.125 b Geriatric adults appear to tolerate therapy less well (e.g., possible higher incidence of adverse GI effects, greater risk of developing renal decompensation) than younger individuals.125 b Fatal adverse GI effects reported more frequently in geriatric patients than younger adults.125 b

Substantially eliminated by kidneys; periodic monitoring of renal function may be useful since geriatric patients are more likely to have decreased renal function.125 (See Geriatric Patients under Dosage and Administration and Renal Impairment under Cautions.)

Renal Impairment

Use not recommended in patients with preexisting renal disease or substantial renal impairment.125

Common Adverse Effects

Abdominal pain,125 constipation,125 diarrhea,125 dyspepsia,125 flatulence,125 gross bleeding/perforation,125 heartburn,125 nausea,125 GI ulcers (gastric/duodenal),125 vomiting,125 abnormal renal function,125 anemia,125 dizziness,125 edema,125 elevated liver enzymes,125 headaches,125 increased bleeding time,125 pruritus,125 rashes,125 tinnitus.125

Interactions for Ponstel

Protein-bound Drugs

Possible pharmacokinetic interaction; potential for mefenamic acid to be displaced from binding sites by, or to displace from binding sites, other protein-bound drugs (e.g., oral anticoagulants, hydantoins, salicylates, sulfonamides, and sulfonylureas).125 a f Observe for adverse effects if used with other protein-bound drugs.a

Drugs Affecting Hepatic Microsomal Enzymes

Inhibitors of CYP2C9: possible altered safety and efficacy of mefenamic acid.125

Specific Drugs

Drug

Interaction

Comments

ACE inhibitors

Reduced BP response to ACE inhibitor possible 125 128 b

Possible deterioration of renal function in individuals with renal impairment128

Monitor BP128

Angiotensin II receptor antagonists

Reduced BP response to angiotensin II receptor antagonist possible128

Possible deterioration of renal function in individuals with renal impairment128

Monitor BP128

Antacids (magnesium-containing)

Increased peak plasma concentrations and AUC of mefenamic acid125 d

Anticoagulants (e.g., warfarin)

Possible bleeding complications125 128 a b e

Use with caution; frequent monitoring of PT advised125 128 a e

Aspirin

Increased risk of GI ulceration or other complications 125 128 b

No consistent evidence that low-dose aspirin mitigates the increased risk of serious cardiovascular events associated with NSAIAs125 b

Concomitant use generally not recommended125 b

Diuretics (furosemide, thiazides)

Reduced natriuretic effects possible125 b

Monitor for diuretic efficacy and renal failure125 b

Lithium

Increased plasma lithium concentrations105 125 b

Monitor for lithium toxicity105 125 b

Methotrexate

Possible toxicity associated with increased plasma methotrexate concentrations during concomitant NSAIA use125 b

Caution advised125 b

Ponstel Pharmacokinetics

Absorption

Bioavailability

Rapidly absorbed following oral administration.125 a Peak plasma concentrations usually attained within 2–4 hours.125 a

Food

Effect of food on rate and extent of absorption not known.125

Distribution

Extent

Appears to cross the placenta.g

Distributed into milk in small amounts.125 c

Plasma Protein Binding

>90%.125

Elimination

Metabolism

Metabolized by CYP2C9 to 3′-hydroxymethyl mefenamic acid; further oxidation to 3′-carboxymefenamic acid may occur. 125 Mefenamic acid and its metabolites also are glucuronidated.125

Elimination Route

Excreted in urine (52%) primarily as glucuronic acid conjugates of the drug and its metabolites and in feces (<20%).125

Half-life

Mefenamic acid: approximately 2 hours.125 Half-lives of 3′-hydroxymethyl mefenamic acid and 3′-carboxymefenamic acid may be longer than parent compound.125

Special Populations

Half-life 5 times longer in preterm infants compared with adults.125

In patients with renal or hepatic impairment, clearance of metabolites may be decreased.125

Not substantially removed by hemodialysis.125 a

Stability

Storage

Oral

Capsules

20–25°C (may be exposed to 15–30°C).125 a

Actions

  • Inhibits cyclooxygenase-1 (COX-1) and COX-2.117 118 119 120 121 122

  • Pharmacologic actions similar to those of other prototypical NSAIAs; exhibits anti-inflammatory, analgesic, and antipyretic activity.125 a

Advice to Patients

  • Importance of reading the medication guide for NSAIAs that is provided to the patient each time the drug is dispensed.125 b

  • Risk of serious cardiovascular events with long-term use.125 133 134 135 136 b Importance of notifying clinician if signs and symptoms of a cardiovascular event (chest pain, dyspnea, weakness, slurred speech) occur.125 b

  • Risk of GI bleeding and ulceration.100 104 125 b Importance of notifying a clinician if signs and symptoms of serious adverse GI effects occur.125 b

  • Importance of discontinuing mefenamic acid and contacting clinician if rash or other signs of hypersensitivity (blisters, fever, pruritus) develop.125 b Importance of seeking immediate medical attention if an anaphylactic reaction occurs.125 b

  • Risk of hepatotoxicity.125 b Importance of discontinuing therapy and contacting a clinician immediately if signs and symptoms of hepatotoxicity (nausea, fatigue, lethargy, pruritus, jaundice, upper right quadrant tenderness, flu-like symptoms) occur.125 b

  • Importance of notifying clinician if signs and symptoms of unexplained weight gain or edema develop.125 b

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.125 Importance of avoiding mefenamic acid in late pregnancy (third trimester).125

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.125

  • Importance of informing patients of other important precautionary information.125 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Mefenamic Acid

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules

250 mg*

Ponstel

First Horizon

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Mefenamic Acid 250MG Capsules (PADDOCK): 30/$429.99 or 90/$1,196.01

Ponstel 250MG Capsules (SHIONOGI PHARMA): 100/$1,843.40 or 300/$5,446.66

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions November 1, 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

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