Mefenamic acid is a member of the anthranilic acid derivatives (or fenamate) class of

nonsteroidal anti-inflammatory drug Non-steroidal anti-inflammatory drugs (NSAID) are members of a Indication (medicine), therapeutic drug class which Analgesic, reduces pain, Anti-inflammatory, decreases inflammation, Antipyretic, decreases fever, and Antithrombotic, prevents bl ...

s (NSAIDs), and is used to treat mild to moderate pain. Its name derives from its systematic name, dimethylphenylaminobenzoic acid. It was discovered and brought to market by

Parke-Davis Parke-Davis is a subsidiary of the pharmaceutical company Pfizer. Although Parke, Davis & Co. is no longer an independent corporation, it was once America's oldest and largest drug maker, and played an important role in medical history. In 1970 ...

as Ponstel in the 1960s. It became generic in the 1980s and is available worldwide under many brand names such as ''Meftal''.

Medical uses

Mefenamic acid is used to treat pain and inflammation in

rheumatoid arthritis Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects synovial joint, joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and h ...

and

osteoarthritis Osteoarthritis is a type of degenerative joint disease that results from breakdown of articular cartilage, joint cartilage and underlying bone. A form of arthritis, it is believed to be the fourth leading cause of disability in the world, affect ...

, postoperative pain, acute pain including

muscle Muscle is a soft tissue, one of the four basic types of animal tissue. There are three types of muscle tissue in vertebrates: skeletal muscle, cardiac muscle, and smooth muscle. Muscle tissue gives skeletal muscles the ability to muscle contra ...

and

back pain Back pain (Latin: ''dorsalgia'') is pain felt in the back. It may be classified as neck pain (cervical), middle back pain (thoracic), lower back pain (lumbar) or coccydynia (tailbone or sacral pain) based on the segment affected. The lumbar area ...

toothache Toothaches, also known as dental pain or tooth pain,Segen JC. (2002). ''McGraw-Hill Concise Dictionary of Modern Medicine''. The McGraw-Hill Companies. is pain in the teeth or their supporting structures, caused by dental diseases or referred ...

and menstrual pain, as well as being prescribed for

menorrhagia Heavy menstrual bleeding (HMB), previously known as menorrhagia or hematomunia, is a menstrual period with excessively heavy flow. It is a type of abnormal uterine bleeding (AUB). Abnormal uterine bleeding can be caused by structural abnorm ...

. In a 10-year study, mefenamic acid and other oral medicines (

tranexamic acid Tranexamic acid is a medication used to treat or prevent excessive blood loss from major trauma, postpartum bleeding, surgery, tooth removal, nosebleeds, and heavy menstruation. It is also used for hereditary angioedema. It is taken eithe ...

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

migraine headache Migraine (, ) is a complex neurological disorder characterized by episodes of moderate-to-severe headache, most often unilateral and generally associated with nausea, and light and sound sensitivity. Other characterizing symptoms may includ ...

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 Menstruation (also known as a period, among other colloquial terms) is the regular discharge of blood and Mucous membrane, mucosal tissue from the endometrium, inner lining of the uterus through the vagina. The menstrual cycle is characterized ...

. Mefenamic acid is recommended to be taken with food.

Contraindications

Mefenamic acid is contraindicated in people who have shown

hypersensitivity Hypersensitivity (also called hypersensitivity reaction or intolerance) is an abnormal physiological condition in which there is an undesirable and adverse immune response to an antigen. It is an abnormality in the immune system that causes Imm ...

reactions such as

urticaria Hives, also known as urticaria, is a kind of skin rash with red or flesh-colored, raised, itchy bumps. Hives may burn or sting. The patches of rash may appear on different body parts, with variable duration from minutes to days, and typically ...

and

asthma Asthma is a common long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Symptoms include episodes of wh ...

to this drug or to other NSAIDs (e.g.

aspirin Aspirin () is the genericized trademark for acetylsalicylic acid (ASA), a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and inflammation, and as an antithrombotic. Specific inflammatory conditions that aspirin is ...

); those with

peptic ulcer Peptic ulcer disease is when the inner part of the stomach's gastric mucosa (lining of the stomach), the first part of the small intestine, or sometimes the lower esophagus, gets damaged. An ulcer in the stomach is called a gastric ulcer, while ...

s or chronic inflammation of the

gastrointestinal tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the Digestion, digestive system that leads from the mouth to the anus. The tract is the largest of the body's systems, after the cardiovascula ...

; those with

kidney In humans, the kidneys are two reddish-brown bean-shaped blood-filtering organ (anatomy), organs that are a multilobar, multipapillary form of mammalian kidneys, usually without signs of external lobulation. They are located on the left and rig ...

liver disease Liver disease, or hepatic disease, is any of many diseases of the liver. If long-lasting it is termed chronic liver disease. Although the diseases differ in detail, liver diseases often have features in common. Liver diseases File:Ground gla ...

;

heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome caused by an impairment in the heart's ability to Cardiac cycle, fill with and pump blood. Although symptoms vary based on which side of the heart is affected, HF ...

; after

coronary artery bypass surgery Coronary artery bypass surgery, also known as coronary artery bypass graft (CABG, pronounced "cabbage"), is a surgical procedure to treat coronary artery disease (CAD), the buildup of plaques in the arteries of the heart. It can relieve chest ...

; and during the third trimester of pregnancy.

Side effects

Known mild

side effects In medicine, a side effect is an effect of the use of a medicinal drug or other treatment, usually adverse but sometimes beneficial, that is unintended. Herbal and traditional medicines also have side effects. A drug or procedure usually used ...

of mefenamic acid include

headache A headache, also known as cephalalgia, is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of Depression (mood), depression in those with severe ...

s, nervousness, and

vomiting Vomiting (also known as emesis, puking and throwing up) is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose. Vomiting can be the result of ailments like food poisoning, gastroenteritis, pre ...

. Potentially serious side effects may include

diarrhea Diarrhea (American English), also spelled diarrhoea or diarrhœa (British English), is the condition of having at least three loose, liquid, or watery bowel movements in a day. It often lasts for a few days and can result in dehydration d ...

gastrointestinal perforation Gastrointestinal perforation, also known as gastrointestinal rupture, is a hole in the wall of the gastrointestinal tract. The gastrointestinal tract is composed of hollow digestive organs leading from the mouth to the anus. Symptoms of gastroi ...

, peptic ulcers,

hematemesis Hematemesis is the vomiting of blood. It can be confused with hemoptysis (coughing up blood) or epistaxis (nosebleed), which are more common. The source is generally the upper gastrointestinal tract, typically above the suspensory muscle of du ...

(vomiting blood), skin reactions (rashes, itching, swelling; in rare cases

toxic epidermal necrolysis Toxic epidermal necrolysis (TEN), also known as Lyell's syndrome, is a type of severe skin reaction. Together with Stevens–Johnson syndrome (SJS) it forms a spectrum of disease, with TEN being more severe. Early symptoms include fever and f ...

) and rarely blood cell disorders such as

agranulocytosis Agranulocytosis, also known as agranulosis or granulopenia, is an acute condition involving a severe and dangerous lowered white blood cell count (leukopenia, most commonly of neutrophils) and thus causing neutropenia in the circulating blood. I ...

. 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 The ductus arteriosus, also called the ductus Botalli, named after the Italian physiologist Leonardo Botallo, is a blood vessel in the developing fetus connecting the trunk of the pulmonary artery to the proximal descending aorta. It allows mos ...

in pregnancy. In October 2020, the U.S.

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...

(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. 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 Drug rash with eosinophilia and systemic symptoms or drug reaction with eosinophilia and systemic symptoms (DRESS), also termed drug-induced hypersensitivity syndrome (DIHS), is a rare reaction to certain medications. It involves primarily a wi ...

due to use of mefenamic acid.

Overdose

Symptoms of overdosing include

kidney failure Kidney failure, also known as renal failure or end-stage renal disease (ESRD), is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney fa ...

gastrointestinal The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The tract is the largest of the body's systems, after the cardiovascular system. ...

problems, bleeding, rashes, confusion,

hallucination A hallucination is a perception in the absence of an external stimulus that has the compelling sense of reality. They are distinguishable from several related phenomena, such as dreaming ( REM sleep), which does not involve wakefulness; pse ...

vertigo Vertigo is a condition in which a person has the sensation that they are moving, or that objects around them are moving, when they are not. Often it feels like a spinning or swaying movement. It may be associated with nausea, vomiting, perspira ...

seizure A seizure is a sudden, brief disruption of brain activity caused by abnormal, excessive, or synchronous neuronal firing. Depending on the regions of the brain involved, seizures can lead to changes in movement, sensation, behavior, awareness, o ...

s, and loss of consciousness. It is treated with induction of vomiting,

gastric lavage Gastric lavage, also commonly called stomach pumping or gastric irrigation or gastric suction, is the process of cleaning out the contents of the stomach using a tube. Since its first recorded use in the early 19th century, it has become one of the ...

bone char Bone char () is a porous, black, granular material produced by charring animal bones. Its composition varies depending on how it is made; however, it consists mainly of tricalcium phosphate (or hydroxyapatite) 57–80%, calcium carbonate 6–10% ...

, and control of

electrolytes An electrolyte is a substance that conducts electricity through the movement of ions, but not through the movement of electrons. This includes most soluble salts, acids, and bases, dissolved in a polar solvent like water. Upon dissolving, t ...

and vital functions.

Interactions

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 Warfarin, sold under the brand name Coumadin among others. It is used as an anticoagulant, anticoagulant medication. It is commonly used to prevent deep vein thrombosis and pulmonary embolism, and to protect against stroke in people who ha ...

and

phenprocoumon Phenprocoumon (marketed under the brand names Marcoumar, Marcumar and Falithrom) is a long-acting anticoagulant to be taken by mouth, and a coumarin derivative. It acts as a vitamin K antagonist and inhibits blood clotting (coagulation) by blocki ...

because it displaces them from their

plasma protein Plasma proteins, sometimes referred to as blood proteins, are proteins present in blood plasma. They perform many different functions, including transport of hormones, vitamins and minerals in activity and functioning of the immune system. Other b ...

binding and increases their free concentrations in the bloodstream. It adds to the risk of gastrointestinal ulcera associated with

corticosteroid Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are invo ...

s and

selective serotonin reuptake inhibitor Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs that are typically used as antidepressants in the treatment of major depressive disorder, anxiety disorders, and other psychological conditions. SSRIs primarily work by blo ...

s. It can increase the risk for adverse effects of

methotrexate Methotrexate, formerly known as amethopterin, is a chemotherapy agent and immunosuppressive drug, immune-system suppressant. It is used to treat cancer, autoimmune diseases, and ectopic pregnancy, ectopic pregnancies. Types of cancers it is u ...

and

lithium Lithium (from , , ) is a chemical element; it has chemical symbol, symbol Li and atomic number 3. It is a soft, silvery-white alkali metal. Under standard temperature and pressure, standard conditions, it is the least dense metal and the ...

by lowering their excretion via the kidneys. It can increase the kidney toxicity of

ciclosporin Ciclosporin, also spelled cyclosporine and cyclosporin, is a calcineurin inhibitor, used as an immunosuppressant medication. It is taken Oral administration, orally or intravenously for rheumatoid arthritis, psoriasis, Crohn's disease, nephr ...

and

tacrolimus Tacrolimus, sold under the brand name Prograf among others, is an immunosuppressive drug. After Allotransplantation, allogenic organ transplant, the risk of organ Transplant rejection, rejection is moderate. To lower the risk of organ rejectio ...

. Combination with

antihypertensive drug Antihypertensives are a class of drugs that are used to treat hypertension (high blood pressure). Antihypertensive therapy seeks to prevent the complications of high blood pressure, such as stroke, heart failure, kidney failure and myocardial infa ...

s such as

ACE inhibitor Angiotensin-converting-enzyme inhibitors (ACE inhibitors) are a class of medication used primarily for the treatment of high blood pressure and heart failure. This class of medicine works by causing relaxation of blood vessels as well as a decr ...

sartan Angiotensin II receptor blockers (ARBs), formally angiotensin II receptor type 1 (AT1) antagonists, also known as angiotensin receptor blockers, angiotensin II receptor antagonists, or AT1 receptor antagonists, are a group of pharmaceuticals tha ...

s and

diuretic A diuretic () is any substance that promotes diuresis, the increased production of urine. This includes forced diuresis. A diuretic tablet is sometimes colloquially called a water tablet. There are several categories of diuretics. All diuretics ...

s 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 (or fenamate) class of

NSAID Non-steroidal anti-inflammatory drugs (NSAID) are members of a therapeutic drug class which reduces pain, decreases inflammation, decreases fever, and prevents blood clots. Side effects depend on the specific drug, its dose and duration of ...

s, it inhibits both isoforms of the enzyme

cyclooxygenase Cyclooxygenase (COX), officially known as prostaglandin-endoperoxide synthase (PTGS), is an enzyme (specifically, a family of isozymes, ) that is responsible for biosynthesis of prostanoids, including thromboxane and prostaglandins such a ...

(

COX-1 Cyclooxygenase 1 (COX-1), also known as prostaglandin-endoperoxide synthase 1 ( HUGO PTGS1), is an enzyme that in humans is encoded by the ''PTGS1'' gene. In humans it is one of three cyclooxygenases. History Cyclooxygenase (COX) is the centr ...

and

COX-2 Cyclooxygenase-2 (COX-2), also known as prostaglandin-endoperoxide synthase 2 ( HUGO PTGS2), is an enzyme that in humans is encoded by the ''PTGS2'' gene. In humans it is one of three cyclooxygenases. It is involved in the conversion of arachid ...

). This prevents formation of

prostaglandin Prostaglandins (PG) are a group of physiology, physiologically active lipid compounds called eicosanoids that have diverse hormone-like effects in animals. Prostaglandins have been found in almost every Tissue (biology), tissue in humans and ot ...

s, which play a role in pain sensitivity, inflammation and fever, but also in

hemostasis In biology, hemostasis or haemostasis is a process to prevent and stop bleeding, meaning to keep blood within a damaged blood vessel (the opposite of hemostasis is hemorrhage). It is the first stage of wound healing. Hemostasis involves three ...

, kidney function, sustaining of pregnancy, and protection of the

gastric mucosa The gastric mucosa is the mucous membrane layer of the stomach, which contains the gastric pits, to which the gastric glands empty. In humans, it is about one mm thick, and its surface is smooth, soft, and velvety. It consists of simple secretor ...

Pharmacokinetics

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

blood plasma Blood plasma is a light Amber (color), amber-colored liquid component of blood in which blood cells are absent, but which contains Blood protein, proteins and other constituents of whole blood in Suspension (chemistry), suspension. It makes up ...

after one to four hours. When in the bloodstream, over 90% of the substance are bound to

s. It probably crosses the

placenta The placenta (: placentas or placentae) is a temporary embryonic and later fetal organ that begins developing from the blastocyst shortly after implantation. It plays critical roles in facilitating nutrient, gas, and waste exchange between ...

, and is found in the breast milk in small amounts. It is metabolized by the liver enzyme

CYP2C9 Cytochrome P450 family 2 subfamily C member 9 (abbreviated CYP2C9) is an enzyme protein. The enzyme is involved in the metabolism, by oxidation, of both xenobiotics, including drugs, and endogenous compounds, including fatty acids. In humans, t ...

to the only weakly active 3'-hydroxymethylmefenamic acid. 3'-carboxymefenamic acid has also been identified as a metabolite, as well as carboxy

glucuronide A glucuronide, also known as glucuronoside, is any substance produced by linking glucuronic acid to another substance via a glycosidic bond. The glucuronides belong to the glycosides. Glucuronidation, the conversion of chemical compounds to glucu ...

s 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 Biological half-life (elimination half-life, pharmacological half-life) is the time taken for concentration of a drug, biological substance (such as a medication) to decrease from its maximum concentration (chemistry), concentration (Cmax (pharm ...

of two hours; the half-life of its metabolites may be longer.

History

Scientists led by Claude Winder from

invented mefenamic acid in 1961, along with fellow members of the class of anthranilic acid derivatives, flufenamic acid in 1963 and

meclofenamate sodium Meclofenamic acid (used as meclofenamate sodium, brand name Meclomen) is a drug used for joint, muscular pain, arthritis and dysmenorrhea. It is a member of the anthranilic acid derivatives (or fenamate) class of nonsteroidal anti-inflammatory d ...

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''.

Chemistry

Synthesis

Analogous to

fenamic acid Fenamic acid is an organic compound, which, especially in its ester form, is called fenamate. serves as a parent structure for several nonsteroidal anti-inflammatory drugs (NSAIDs), including mefenamic acid, tolfenamic acid, flufenamic acid, and ...

, this compound may be made from 2-chlorobenzoic acid and 2,3-dimethylaniline.

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. Recent experimental studies have unveiled two additional hidden conformers of mefenamic acid. 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 but also in supercritical fluids, aerogels, and lipid bilayers. 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. 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. By contrast, in the UK, a weeks supply is £1.66, or £8.17 for branded Ponstan. In New Zealand, a weeks's supply of Ponstan costs NZ$9.08, around US$5.50.

Research

While studies have been conducted to see if mefenamic acid can improve behavior in transgenic mouse models of

Alzheimer's disease Alzheimer's disease (AD) is a neurodegenerative disease and the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As the disease advances, symptoms can include problems wit ...

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.