Mefenamic acid

Mefenamic acid

Systematic (IUPAC) name

2-(2,3-dimethylphenyl)aminobenzoic acid

Clinical data

Trade names Ponstel, Ponstan

AHFS/Drugs.com monograph

MedlinePlus a681028

Pregnancy cat. C (Australia, United States)

Legal status Pharmacy Only (S2) (AU) ℞-only (U.S.), POM in UK

Routes Oral
 Pharmacokinetic data

Bioavailability 90%

Protein binding 90%

Metabolism Hepatic (CYP2C9)

Half-life 2 hours

Excretion Renal and fecal

Identifiers

CAS number 61-68-7

ATC code M01AG01

PubChem CID 4044

IUPHAR ligand 2593

DrugBank DB00784

ChemSpider 3904

UNII 367589PJ2C

KEGG D00151

ChEMBL CHEMBL686

Chemical data

Formula C15H15NO2
 Mol. mass 241.285 g/mol

SMILES[show]

InChI[show]

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Mefenamic acid is a non-steroidal anti-inflammatory drug used to treat pain, including menstrual pain. It is
typically prescribed for oral administration. Mefenamic acid is marketed in the USA as Ponstel and is
commonly known in UK as Ponstan.

Mefenamic acid decreases inflammation (swelling) and uterine contractions by a still unknown mechanism.
However it is thought to be related to the inhibition of prostaglandin synthesis. There is also evidence that
supports the use of mefenamic acid for perimenstrual migraine headache prophylaxis, with treatment starting 2
days prior to the onset of flow or 1 day prior to the expected onset of the headache and continuing for the
duration ofmenstruation.[1]

Since hepatic metabolism plays a significant role in mefenamic acid elimination, patients with
known liver deficiency may be prescribed lower doses.Kidney deficiency may also cause accumulation of the
drug and its metabolites in the excretory system. Therefore patients suffering from renal conditions should not
be prescribed mefenamic acid.

Availability

TABLETS 100 mg, 250 mg, 500 mg. CAPSULES: 250 mg. SUSPENSION: 50 mg/5 ml [2]

Mechanism of action

Mefenamic acid is a competitive inhibitor of COX-1 and COX-2, which are responsible for the first committed
step in prostaglandin biosynthesis.[3]Decreasing the activity of these enzymes thus reduces the production of
prostaglandins, which are implicated in inflammation and pain processes.[4]

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. [5]

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%) [6]

Side effects

Known mild side effects of mefenamic acid include headaches, nervousness and emesis. Serious side effects
may include diarrhoea, haematemesis (vomiting blood), haematuria (blood in urine),blurred vision,
skin rash, pruritus, oedema, sore throat and fever. It is advised to consult a doctor immediately if
these symptoms appear while taking this medication.

Mefenamic acid is recommended to be taken with food.[7]

Overdose

Overdose can lead to a range of symptoms

including convulsions, nausea, emesis, haematemesis, bradypnea, coma. Onset of symptoms is usually
between 30 minutes and 4 hours, but signs of renal failure may appear several days after an overdose. Seek
medical attention immediately in the case of overdose. The lethal dose can be as low as 2.5g.

Synthesis

Analogous to fenamic acid, this compound may be synthesized from 2-chlorobenzoic acid and 2,3-
dimethylaniline.[8]

Precautions

Mefenamic Acid 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 in reducing fever and inflammation may
diminish the utility of these diagnostic signs in detecting complications of presumed noninfectious, painful
conditions. Renal and hepatic impairment, asthma. Monitor blood counts and liver function during long-term
therapy.[9]

Brand names

Beafemic, Mefalth, Mefalth T, Mefivan, Ponstel, Ponstan, Ponstal, Parkemed, Revalan, Mafepain, Mefamed,
Mephadolor, Meftal, Dyfenamic, Potalon, Dolfenal, Meyerdonal, Alfoxan, Fenagesic, Fenamin, Spiralgin,
Almus, Mefacit.

References

1. ^ Pringsheim, T.; Davenport, W. J.; Dodick, D. (2008). "Acute Treatment and Prevention of Menstrually
Related Migraine Headache: Evidence-Based Review". Neurology 70 (17): 1555–1563.PMID 18427072.

2. ^ National formulary of India, 4th Ed. New Delhi, India, Indian Pharmacopoeia commission; 2011: 7

3. ^ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2720641/

4. ^ http://onlinelibrary.wiley.com/doi/10.1038/sj.bjp.0704092/abstract;jsessionid=62C075BC55DE8389CE3C5

6CBD0035181.d03t03

5. ^ http://www.drugs.com/ppa/mefenamic-acid.html

6. ^ http://www.drugs.com/ppa/mefenamic-acid.html

7. ^ "Side effects for Mefenamic Acid". Medline Plus. National Institutes of Health.

8. ^ Trinus, F. P.; Mokhort, N. A.; Yagupol'skii, L. M.; Fadeicheva, A. G.; Danilenko, V. S.; Ryabukha, T. K.;

Fialkov, Yu. A.; Kirichek, L. M.; Endel'man, É. S.; Get'man, G. A. (1977). "Mefenamic acid — A Nonsteroid
Antiinflammatory Agent". Pharmaceutical Chemistry Journal 11 (12): 1706–1711. doi:10.1007/BF00778304.

9. ^ http://www.drugsupdate.com/generic/view/285