Mefenamic acid

Source: Wikipedia, the free encyclopedia.
Mefenamic acid
Clinical data
Trade namesPonstel, Ponstan, others
AHFS/Drugs.comMonograph
MedlinePlusa681028
Pregnancy
category
  • AU: C
Routes of
administration		By mouth, rectal
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability90%
Protein binding>90%
MetabolismLiver (CYP2C9)
Elimination half-life2 hours
ExcretionKidney (52–67%), faeces (20–25%)
Identifiers
  • 2-(2,3-dimethylphenyl)aminobenzoic acid
JSmol)
  • O=C(O)c2c(Nc1cccc(c1C)C)cccc2
  • InChI=1S/C15H15NO2/c1-10-6-5-9-13(11(10)2)16-14-8-4-3-7-12(14)15(17)18/h3-9,16H,1-2H3,(H,17,18) checkY
  • Key:HYYBABOKPJLUIN-UHFFFAOYSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Mefenamic acid is a member of the anthranilic acid derivatives (or fenamate) class of nonsteroidal anti-inflammatory drugs (NSAIDs), and is used to treat mild to moderate pain.[3][4]

Its name derives from its systematic name, dimethylphenylaminobenzoic acid. It was discovered and brought to market by Parke-Davis as Ponstel in the 1960s. It became generic in the 1980s and is available worldwide under many brand names such as Meftal.[5]

Medical uses

Mefenamic acid is used to treat pain and inflammation in

menorrhagia.[6][7][8] In a 10-year study, mefenamic acid and other oral medicines (tranexamic acid) were as effective as the levonorgestrel intrauterine coil; the same proportion of women had not had surgery for heavy bleeding and had similar improvements in their quality of life.[9][10]

There is evidence that supports the use of mefenamic acid for perimenstrual

migraine headache prophylaxis, with treatment starting two days prior to the onset of flow or one day prior to the expected onset of the headache and continuing for the duration of menstruation.[4]

Mefenamic acid is recommended to be taken with food.[11]

Contraindications

Mefenamic acid is contraindicated in people who have shown

peptic ulcers or chronic inflammation of the gastrointestinal tract; those with kidney or liver disease; heart failure; after coronary artery bypass surgery; and during the third trimester of pregnancy.[7][12]

Side effects

Known mild side effects of mefenamic acid include headaches, nervousness, and vomiting. Potentially serious side effects may include diarrhea, gastrointestinal perforation, peptic ulcers, hematemesis (vomiting blood), skin reactions (rashes, itching, swelling; in rare cases toxic epidermal necrolysis) and rarely blood cell disorders such as agranulocytosis.[13][7] It has been associated with acute liver damage.[14]

In 2008 the US label was updated with a warning concerning a risk of premature closure of the ductus arteriosus in pregnancy.[15]

In October 2020, the U.S. Food and Drug Administration (FDA) required the drug label to be updated for all nonsteroidal anti-inflammatory medications to describe the risk of kidney problems in unborn babies that result in low amniotic fluid.[16][17] They recommend avoiding NSAIDs in pregnant women at 20 weeks or later in pregnancy.[16][17]

In its November 2023 monthly drug safety alert under the Pharmacovigilance Programme of India (PvPI), the Indian Pharmacopoeia Commission flagged a risk of DRESS Syndrome due to use of mefenamic acid.[18]

Overdose

Symptoms of overdosing include

electrolytes and vital functions.[7]

Interactions

Interactions are broadly similar to those of other NSAIDs. Mefenamic acid interferes with the anti–blood clotting mechanism of Aspirin. It increases the

sartans and diuretics can decrease their effectiveness as well as increase the risk for kidney toxicity.[7][8]

Pharmacology

Mechanism of action

Main article: Nonsteroidal anti-inflammatory drug § Mechanism of action

Like other members of the anthranilic acid derivatives (or fenamate) class of

COX-2). This prevents formation of prostaglandins,[14][19] which play a role in pain sensitivity, inflammation and fever, but also in hemostasis, kidney function, sustaining of pregnancy, and protection of the gastric mucosa.[20]

Pharmacokinetics

carboxy groups at the bottom right of each substance can be glucuronidized
.

Mefenamic acid is rapidly absorbed from the gut and reaches highest concentrations in the

plasma proteins. It probably crosses the placenta, and is found in the breast milk in small amounts.[7][12]

It is metabolized by the liver enzyme

carboxy glucuronides of all three substances. Mefenamic acid and its metabolites are excreted via the urine (52–67%) and the faeces (20–25%, or less than 20% following another source). The parent substance has a biological half-life of two hours; the half-life of its metabolites may be longer.[7][8][12]

History

Scientists led by Claude Winder from

meclofenamate sodium in 1964.[21] U.S. Patent 3,138,636 on the drug was issued in 1964.[22][23]

It was approved in the UK in 1963 as Ponstan, in West Germany in 1964 as Ponalar and in France as Ponstyl, and the US in 1967 as Ponstel.[14][23]

Chemistry

Synthesis

Analogous to

2,3-dimethylaniline.[24]

Conformational flexibility

Mefenamic acid, a member of the fenamate, is a chemical compound derived from anthranilic acid . This derivative is created by substituting one of the hydrogen atoms attached to the nitrogen atom with a 2,3-dimethylphenyl fragment. The result is a structurally complex molecule with fascinating conformational properties.

The mefenamic acid molecule exhibits conformational lability, meaning it can exist in various shapes or conformers. This flexibility arises from changes in the position of the carboxylic acid group and the 2,3-dimethylphenyl fragment about the anthranil moiety. Specifically, the arrangement of the substituted benzene fragments relative to each other plays a crucial role in determining the different polymorphic forms of mefenamic acid.[25]

Recent experimental studies have unveiled two additional hidden conformers of mefenamic acid.[26] These conformers result from alterations in the positions of hydroxyl groups within the molecule. This discovery adds to our understanding of the compound's structural diversity.

External factors, including temperature, pressure, and the surrounding medium, highly influence the conformational state of mefenamic acid. Researchers have conducted extensive investigations into its spatial structure not only in organic solvents[27] but also in supercritical fluids,[28][29] aerogels,[30] and lipid bilayers.[31][32] These studies have helped elucidate the impact of different environments on the molecule's conformation.

Society and culture

Availability and pricing

Mefenamic acid is generic and is available worldwide under many brand names.[5]

In the US, wholesale price of a week's supply of generic mefenamic acid has been quoted as $426.90 in 2014. Brand-name Ponstel is $571.70.[33] By contrast, in the UK, a weeks supply is £1.66, or £8.17 for branded Ponstan.[34]

Research

While studies have been conducted to see if mefenamic acid can improve behavior in transgenic mouse models of Alzheimer's disease[35][36] there is little evidence that mefenamic acid or other NSAIDs can treat or prevent Alzheimer's in humans; clinical trials of NSAIDs other than mefenamic acid for treatment of Alzheimer's have found more harm than benefit.[37][38][39] A small controlled study of 28 human subjects showed improved cognitive impairment using mefenamic acid non-steroidal anti-inflammatory therapy.[40]

References

  1. FDA
    . Retrieved 22 Oct 2023.
  2. ^ "Prescription medicines: registration of new generic medicines and biosimilar medicines, 2017". Therapeutic Goods Administration (TGA). 21 June 2022. Retrieved 30 March 2024.
  3. ^ "Ponstel Label" (PDF). U.S. Food and Drug Administration. 19 February 2008.
  4. ^
    S2CID 27966664
    .
  5. ^ a b "International listings for mefenamic acid". Drugs.com. Retrieved 3 July 2015.
  6. doi:10.18578/bnf.855907230
    . Retrieved 2020-04-18.
  7. ^ a b c d e f g Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag. 2020. Parkemed 500 mg-Filmtabletten.
  8. ^ a b c "mediQ: Mefenaminsäure". Retrieved 2020-07-23.
  9. PMID 37924269
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  10. doi:10.3310/nihrevidence_62335
    .
  11. ^ "Side effects for Mefenamic Acid". Medline Plus. National Institutes of Health.
  12. ^ a b c Cerner Multum. "Mefenamic Acid". Drugs.com. Retrieved 2020-07-22.
  13. ISBN 978-0-08-093294-1
    .
  14. ^
    PMID 31643361
    . Retrieved 28 November 2019.
  15. ^ "Safety Labeling Changes: Ponstel (mefenamic acid capsules, USP)". Center for Drug Evaluation and Research (CDER). U.S. Food and Drug Administration. March 2008. Archived from the original on 4 November 2009.
  16. ^ a b "FDA Warns that Using a Type of Pain and Fever Medication in Second Half of Pregnancy Could Lead to Complications". U.S. Food and Drug Administration (FDA) (Press release). 15 October 2020. Retrieved 15 October 2020. Public Domain This article incorporates text from this source, which is in the public domain.
  17. ^ a b "NSAIDs may cause rare kidney problems in unborn babies". U.S. Food and Drug Administration. 21 July 2017. Retrieved 15 October 2020. Public Domain This article incorporates text from this source, which is in the public domain.
  18. ^ "Monthly Drug Safety Alert". Indian Pharmacopoeia Commission. 30 November 2023. Retrieved 10 December 2023.
  19. PMID 19603831
    .
  20. ISBN 978-3-8047-2898-1
    .
  21. PMID 16378496
    .
  22. ^ US 3,138,636, Scherrer RA, issued 23 June 1964, assigned to Parke Davis and Co LLC 
  23. ^ a b Sittig M (1988). "Mefenamic acid". Pharmaceutical Manufacturing Encyclopedia (PDF). Vol. 1 (Second ed.). Noyes Publications. pp. 918–919. Archived from the original (PDF) on 2007-10-23.
  24. S2CID 45211486
    .
  25. ISSN 1528-7483
    .
  26. PMID 36365095
    .
  27. doi:10.1063/1.5087339
    .
  28. S2CID 256259116
    .
  29. S2CID 259822531
    .
  30. PMID 37108046
    .
  31. S2CID 252747244
    .
  32. PMID 37367811
    .
  33. PMID 25157683
    .
  34. ^ "Access leading drug and healthcare references". www.medicinescomplete.com. Retrieved 19 September 2014.
  35. S2CID 20982844
    .
  36. PMID 27509875
    .
  37. S2CID 35357112
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  38. PMID 22336816
    .
  39. PMID 25227314
    .
  40. PMID 34150033
    .

Further reading

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