|Pronunciation||mef" e nam' ik|
|Trade names||Ponstel, Ponstan, others|
|By mouth, suppositories|
|Elimination half-life||2 hours|
|Excretion||Urine (52–67%), faeces (20–25%)|
|Chemical and physical data|
|Molar mass||241.290 g·mol−1|
|3D model (JSmol)|
|(what is this?)|
Mefenamic acid is a nonsteroidal anti-inflammatory drugs (NSAIDs) used to treat mild to moderate pain including painful periods. Other uses include for inflammation. Such use is recommended for less than a week. It is taken by mouth.
Common side effects include abdominal pain, heartburn, vomiting, kidney problems, fluid retention, and rashes. Other serious side effects may include cardiovascular disease, allergic reactions, stomach ulcers, hemolytic anemia, liver problems, and heart failure. Use is not recommended in the last third of pregnancy and during breastfeeding. Mefenamic acid works by decreasing the production of prostaglandin by the enzyme cyclooxygenase.
Mefenamic acid was approved for medical use in the United States in 1967. It is available as a generic medication. In the United Kingdom 100 tablets of 250 mg costs the NHS about 23 pounds as of 2020. This amount in the United States costs about 135 USD. It is not widely used in the United States due to concerns of relatively greater side effects compared to some other NSAIDs.
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.
The typical dose is 500 mg three times per day in those over the age of 12 years.
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. It has been associated with acute liver damage.
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.
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 Its name derives from its systematic name, dimethylphenylaminobenzoic acid. 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. In the Philippines, 1 tablet of 500 mg generic mefenamic acid cost PHP25.00 (or the equivalent of US$0.50) as of September 2, 2019. In some other countries it is less expensive: for example, in Austria 30 tablets cost between €3.80 and €7.15 as of 2020.
While studies have been conducted to see if mefenamic acid can improve behavior in transgenic mouse models of Alzheimer's disease there is no good 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.
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