|Trade names||Ponstel, Ponstan, many others|
|By mouth, suppositories|
|Elimination half-life||2 hours|
|Excretion||Urine (52–67%), faeces (20–25%)|
|CompTox Dashboard (EPA)|
|Chemical and physical data|
|Molar mass||241.290 g·mol−1|
|3D model (JSmol)|
|(what is this?)|
Its name derives from its systematic name, dimethylphenylaminobenzoic acid. It was discovered and brought to market by Parke-Davis in the 1960s. It became generic in the 1980s and is available worldwide under many brand names such as Meftal.
Mefenamic acid is used to treat pain and inflammation in rheumatoid arthritis and osteoarthritis, postoperative pain, acute pain including muscle and back pain, toothache and menstrual pain, as well as being prescribed for menorrhagia.
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.
Mefenamic acid is recommended to be taken with food.
Mefenamic acid is contraindicated in people who have shown hypersensitivity reactions such as urticaria and asthma to this drug or to other NSAIDs (e.g. aspirin); those with 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.
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.: 334  It has been associated with acute liver damage.
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. They recommend avoiding NSAIDs in pregnant women at 20 weeks or later in pregnancy.
Symptoms of overdosing include kidney failure, gastrointestinal problems, bleeding, rashes, confusion, hallucinations, vertigo, seizures, and loss of consciousness. It is treated with induction of vomiting, gastric lavage, bone char, and control of electrolytes and vital functions.
Interactions are broadly similar to those of other NSAIDs. Mefenamic acid interferes with the anti–blood clotting mechanism of Aspirin. It increases the blood thinning effects of warfarin and phenprocoumon because it displaces them from their plasma protein binding and increases their free concentrations in the bloodstream. It adds to the risk of gastrointestinal ulcera associated with corticosteroids and selective serotonin reuptake inhibitors. It can increase the risk for adverse effects of methotrexate and lithium by lowering their excretion via the kidneys. It can increase the kidney toxicity of ciclosporin and tacrolimus. Combination with antihypertensive drugs such as ACE inhibitors, sartans and diuretics can decrease their effectiveness as well as increase the risk for kidney toxicity.
Mechanism of action
Like other members of the anthranilic acid derivatives (or fenamate) class of NSAIDs, it inhibits both isoforms of the enzyme cyclooxygenase (COX-1 and COX-2). This prevents formation of prostaglandins, 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.
Mefenamic acid is rapidly absorbed from the gut and reaches highest concentrations in the blood plasma after one to four hours. When in the bloodstream, over 90% of the substance are bound to plasma proteins. It probably crosses the placenta, and is found in the breast milk in small amounts.
It is metabolized by the liver enzyme CYP2C9 to the only weakly active 3'-hydroxymethylmefenamic acid. 3'-carboxymefenamic acid has also been identified as a metabolite, as well as 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.
Scientists led by Claude Winder from Parke-Davis invented mefenamic acid in 1961, along with fellow members of the class of anthranilic acid derivatives, flufenamic acid in 1963 and meclofenamate sodium in 1964.: 718 U.S. Patent 3,138,636 on the drug was issued in 1964.: 918–919
Society and culture
Availability and pricing
Mefenamic acid is generic and is available worldwide under many brand names.
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. In contrast, in the UK, a weeks supply is £1.66, or £8.17 for branded Ponstan.
While studies have been conducted to see if mefenamic acid can improve behavior in transgenic mouse models of Alzheimer's disease 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.A small controlled study of 28 human subjects showed improved cognitive impairment using mefenamic acid non-steroidal anti-inflammatory therapy.
- FDA Ponstel Label Updated February 19, 2008
- Pringsheim T, Davenport WJ, Dodick D (April 2008). "Acute treatment and prevention of menstrually related migraine headache: evidence-based review". Neurology. 70 (17): 1555–63. doi:10.1212/01.wnl.0000310638.54698.36. PMID 18427072. S2CID 27966664.
- Drugs.com drugs.com international listings for mefenamic acid Page accessed July 3, 2015
- "Digital Medicines Information Suite". MedicinesComplete. doi:10.18578/bnf.855907230. Retrieved 2020-04-18.
- Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag. 2020. Parkemed 500 mg-Filmtabletten.
- "mediQ: Mefenaminsäure". Retrieved 2020-07-23.
- "Side effects for Mefenamic Acid". Medline Plus. National Institutes of Health.
- Mefenamic Acid Monograph. Accessed 2020-07-22.
- Jeffrey K. Aronson. Meyler's Side Effects of Analgesics and Anti-inflammatory Drugs. Elsevier, 2009 ISBN 9780080932941
- NIH LiverTox Database Mefenamic Acid Last updated June 23, 2015. Page accessed November 28, 2019
- FDA March 2008 FDA advisory
- "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. This article incorporates text from this source, which is in the public domain.
- "NSAIDs may cause rare kidney problems in unborn babies". U.S. Food and Drug Administration. 21 July 2017. Retrieved 15 October 2020. This article incorporates text from this source, which is in the public domain.
- Prusakiewicz JJ, Duggan KC, Rouzer CA, Marnett LJ (August 2009). "Differential sensitivity and mechanism of inhibition of COX-2 oxygenation of arachidonic acid and 2-arachidonoylglycerol by ibuprofen and mefenamic acid". Biochemistry. 48 (31): 7353–5. doi:10.1021/bi900999z. PMC 2720641. PMID 19603831.
- Mutschler, Ernst (2013). Arzneimittelwirkungen. Wissenschaftliche Verlagsgesellschaft Stuttgart. pp. 205–206, 444. ISBN 978-3-8047-2898-1.
- Whitehouse M. Drugs to Treat Inflammation: A Historical Overview. pp 707-729 in Frontiers in Medicinal Chemistry, Volume 4. Eds Rahman A, et al. Bentham Science Publishers, 2009 ISBN 9781608052073
- US Patent 3,138,636
- Marshall Sittig Pharmaceutical Manufacturing Encyclopedia Volume 1 A-K Archived 2007-10-23 at the Wayback Machine Second Edition, Reprint Edition. Noyes Publications, 1988
- Trinus FP, Mokhort NA, Yagupol'skii LM, Fadeicheva AG, Danilenko VS, Ryabukha TK, Fialkov YA, Kirichek LM, Endel'man ÉS, Get'man GA (1977). "Mefenamic acid — A Nonsteroid Antiinflammatory Agent". Pharmaceutical Chemistry Journal. 11 (12): 1706–1711. doi:10.1007/BF00778304. S2CID 45211486.
- Drugs for Osteoarthritis. The Medical Letter, 56(1450):80-84, September 2014
- "Access leading drug and healthcare references". www.medicinescomplete.com. Retrieved 19 September 2014.
- Joo Y, Kim HS, Woo RS, Park CH, Shin KY, Lee JP, Chang KA, Kim S, Suh YH (January 2006). "Mefenamic acid shows neuroprotective effects and improves cognitive impairment in in vitro and in vivo Alzheimer's disease models". Molecular Pharmacology. 69 (1): 76–84. doi:10.1124/mol.105.015206. PMID 16223958. S2CID 20982844.
- Daniels MJ, Rivers-Auty J, Schilling T, Spencer NG, Watremez W, Fasolino V, et al. (August 2016). "Fenamate NSAIDs inhibit the NLRP3 inflammasome and protect against Alzheimer's disease in rodent models". Nature Communications. 7: 12504. Bibcode:2016NatCo...712504D. doi:10.1038/ncomms12504. PMC 4987536. PMID 27509875.
- Miguel-Álvarez M, Santos-Lozano A, Sanchis-Gomar F, Fiuza-Luces C, Pareja-Galeano H, Garatachea N, Lucia A (February 2015). "Non-steroidal anti-inflammatory drugs as a treatment for Alzheimer's disease: a systematic review and meta-analysis of treatment effect". Drugs & Aging. 32 (2): 139–47. doi:10.1007/s40266-015-0239-z. PMID 25644018. S2CID 35357112.
- Jaturapatporn D, Isaac MG, McCleery J, Tabet N (February 2012). "Aspirin, steroidal and non-steroidal anti-inflammatory drugs for the treatment of Alzheimer's disease". The Cochrane Database of Systematic Reviews (2): CD006378. doi:10.1002/14651858.CD006378.pub2. PMID 22336816.
- Wang J, Tan L, Wang HF, Tan CC, Meng XF, Wang C, Tang SW, Yu JT (2015). "Anti-inflammatory drugs and risk of Alzheimer's disease: an updated systematic review and meta-analysis". Journal of Alzheimer's Disease. 44 (2): 385–96. doi:10.3233/JAD-141506. PMID 25227314.
- Melnikov, Valery; Tiburcio-Jimenez, Daniel; Mendoza-Hernandez, Martha A.; Delgado-Enciso, Josuel; De-Leon-Zaragoza, Luis; Guzman-Esquivel, Jose; Rodriguez-Sanchez, Iram P.; Martinez-Fierro, Margarita L.; Lara-Esqueda, Agustin; Delgado-Enciso, Osiris G.; Jacinto-Cortes, Ivan; Zaizar-Fregoso, Sergio A.; Paz-Michel, Brenda A.; Murillo-Zamora, Efren; Delgado-Enciso, Ivan; Galvan-Salazar, Hector R. (2021). "Improve cognitive impairment using mefenamic acid non-steroidal anti-inflammatory therapy: additional beneficial effect found in a controlled clinical trial for prostate cancer therapy". American Journal of Translational Research. 13 (5): 4535–4543. PMC 8205720. PMID 34150033.
- MedlinePlus Drug Information: Mefenamic Acid. Last accessed September 28, 2005.
- Ponstel Pharmacology, Pharmacokinetics, Studies, Metabolism - Mefenamic Acid - RxList Monographs. Last accessed September 28, 2005.
- Consumption of NSAIDs and the Development of Congestive Heart Failure in Elderly Patients
- NSAIDs May Increase Risk for Worsening Heart Failure