Mefenamic acid is a member of the anthranilic acid derivatives class of nonsteroidal anti-inflammatory drugs, and is used to treat mild to moderate pain. It is not widely used in the United States due to its side effects and high cost compared to other NSAIDs. 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. As of 2015 the cost for a typical course of medication in the United States is more than $200. In some other countries it is cheaper: for example, in Austria 30 tablets cost between €3.80 and €7.15 as of 2020.
Medical uses
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.
Known mild side effects of mefenamic acid include headaches, nervousness, and vomiting. Potentially serious side effects may include diarrhea, gastrointestinal perforation, peptic ulcers, hematemesis, skin reactions and rarely blood cell disorders such as agranulocytosis. It has been associated with acute liver damage. In 2008 the US label was updated with a warning concerning a risk of premature closure of the ductus arteriosus in pregnancy.
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.
Pharmacology
Mechanism of action
Like other members of the anthranilic acid derivatives class of NSAIDs, it inhibits both isoforms of the enzyme cyclooxygenase. 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.
Pharmacokinetics
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 enzymeCYP2C9 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 and the faeces. The parent substance has a biological half-life of two hours; the half-life of its metabolites may be longer.
History
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. U.S. Patent 3,138,636 on the drug was issued in 1964. 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.
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 as of September 2, 2019.
Research
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.
