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 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 (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 joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and hands are involv ...

and

osteoarthritis Osteoarthritis (OA) is a type of degenerative joint disease that results from breakdown of joint cartilage and underlying bone which affects 1 in 7 adults in the United States. It is believed to be the fourth leading cause of disability in the w ...

, postoperative pain, acute pain including

muscle Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscl ...

and

back pain Back pain 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 is the most common area ...

toothache Toothache, also known as dental 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 pain referred to the t ...

and

menstrual pain Dysmenorrhea, also known as period pain, painful periods or menstrual cramps, is pain during menstruation. Its usual onset occurs around the time that menstruation begins. Symptoms typically last less than three days. The pain is usually in th ...

, as well as being prescribed for

menorrhagia Heavy menstrual bleeding (HMB), previously known as menorrhagia or hypermenorrhea, is a menstrual period with excessively heavy flow. It is a type of abnormal uterine bleeding Abnormal uterine bleeding (AUB), also known as (AVB) or as atypical ...

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

migraine headache Migraine (, ) is a common neurological disorder characterized by recurrent headaches. Typically, the associated headache affects one side of the head, is pulsating in nature, may be moderate to severe in intensity, and could last from a few hou ...

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 mucosal tissue from the inner lining of the uterus through the vagina. The menstrual cycle is characterized by the rise and fall of hor ...

. 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) refers to undesirable reactions produced by the normal immune system, including allergies and autoimmunity. They are usually referred to as an over-reaction of the immune s ...

reactions such as

urticaria Hives, also known as urticaria, is a kind of skin rash with red, 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 does not leave any long-lasti ...

and

asthma Asthma is a 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 wheezing, cou ...

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

aspirin Aspirin, also known as acetylsalicylic acid (ASA), is a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and/or inflammation, and as an antithrombotic. Specific inflammatory conditions which aspirin is used to treat inc ...

); those with

peptic ulcer Peptic ulcer disease (PUD) is a break in the inner lining of the stomach, the first part of the small intestine, or sometimes the lower esophagus. An ulcer in the stomach is called a gastric ulcer, while one in the first part of the intestines i ...

s or chronic inflammation of the

gastrointestinal tract 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 GI tract contains all the major organ (biology), organs of the digestive syste ...

; those with

kidney The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blood ...

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. Signs and symptoms Some of the sig ...

;

heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, a ...

; 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 pai ...

; and during the third trimester of pregnancy.

Side effects

Known mild

side effects In medicine, a side effect is an effect, whether therapeutic or adverse, that is secondary to the one intended; although the term is predominantly employed to describe adverse effects, it can also apply to beneficial, but unintended, consequence ...

of mefenamic acid include

headache Headache 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 in those with severe headaches. Headaches can occur as a result ...

s, nervousness, and

vomiting Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the Human nose, nose. Vomiting can be the result of ailments like Food-poisoning, foo ...

. Potentially serious side effects may include

diarrhea Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin wi ...

gastrointestinal perforation Gastrointestinal perforation, also known as ruptured bowel, is a hole in the wall of part of the gastrointestinal tract. The gastrointestinal tract includes the esophagus, stomach, small intestine, and large intestine. Symptoms include severe ab ...

, peptic ulcers,

hematemesis Hematemesis is the vomiting of blood. It is always an important sign. 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 abo ...

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

toxic epidermal necrolysis Toxic epidermal necrolysis (TEN) 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 flu-like symptoms. A few days later th ...

) 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 a neutropenia in the circulating blood. ...

. 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 a ...

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 respon ...

(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.

Overdose

Symptoms of overdosing include

kidney failure Kidney failure, also known as end-stage kidney disease, 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 failure is classified as eit ...

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 GI tract contains all the major organs of the digestive system, in humans and ...

problems, bleeding, rashes, confusion,

hallucination A hallucination is a perception in the absence of an external stimulus that has the qualities of a real perception. Hallucinations are vivid, substantial, and are perceived to be located in external objective space. Hallucination is a combinatio ...

vertigo Vertigo is a condition where a person has the sensation of movement or of surrounding objects moving when they are not. Often it feels like a spinning or swaying movement. This may be associated with nausea, vomiting, sweating, or difficulties w ...

seizure An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much of the body with los ...

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

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

bone char Bone char ( lat, carbo animalis) 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%, calci ...

, and control of

electrolytes An electrolyte is a medium containing ions that is electrically conducting through the movement of those ions, but not conducting electrons. This includes most soluble salts, acids, and bases dissolved in a polar solvent, such as water. Upon di ...

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, is a medication that is used as an anticoagulant (blood thinner). It is commonly used to prevent blood clots such as deep vein thrombosis and pulmonary embolism, and to prevent strok ...

and

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

because it displaces them from their

plasma protein Blood-proteins, also termed plasma proteins, are proteins present in blood plasma. They serve many different functions, including transport of lipids, hormones, vitamins and minerals in activity and functioning of the immune system. Other blood pr ...

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 involv ...

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 increase the extracell ...

s. It can increase the risk for adverse effects of

methotrexate Methotrexate (MTX), formerly known as amethopterin, is a chemotherapy agent and immune-system suppressant. It is used to treat cancer, autoimmune diseases, and ectopic pregnancies. Types of cancers it is used for include breast cancer, leuke ...

and

lithium Lithium (from el, λίθος, lithos, lit=stone) is a chemical element with the symbol Li and atomic number 3. It is a soft, silvery-white alkali metal. Under standard conditions, it is the least dense metal and the least dense solid el ...

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 a natural product. It is taken orally or intravenously for rheumatoid arthritis, psoriasis, Crohn's disease, ...

and

tacrolimus Tacrolimus, sold under the brand name Prograf among others, is an immunosuppressive drug. After allogeneic organ transplant, the risk of organ rejection is moderate. To lower the risk of organ rejection, tacrolimus is given. The drug can also ...

. 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 and myocardial infarction. Evidence suggests that r ...

s such as

ACE inhibitor Angiotensin-converting-enzyme inhibitors (ACE inhibitors) are a class of medication used primarily for the treatment of hypertension, high blood pressure and heart failure. They work by causing relaxation of blood vessels as well as a decrease i ...

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 in ...

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 formation of prostanoids, including thromboxane and prostaglandins such as prosta ...

(

COX-1 Cyclooxygenase 1 (COX-1), also known as prostaglandin G/H synthase 1, prostaglandin-endoperoxide synthase 1 or prostaglandin H2 synthase 1, is an enzyme that in humans is encoded by the ''PTGS1'' gene. In humans it is one of two cyclooxygenases. ...

and

COX-2 Prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) (The HUGO official symbol is PTGS2; HGNC ID, HGNC:9605), also known as cyclooxygenase-2 or COX-2, is an enzyme that in humans is encoded by the ''PTGS2'' gene. ...

). This prevents formation of

prostaglandin The prostaglandins (PG) are a group of physiologically active lipid compounds called eicosanoids having diverse hormone-like effects in animals. Prostaglandins have been found in almost every tissue in humans and other animals. They are derive ...

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. This involves coagulation, whi ...

, 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 glands and the gastric pits. In humans, it is about 1 mm thick, and its surface is smooth, soft, and velvety. It consists of simple columnar epithelium, lamina ...

Pharmacokinetics

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

blood plasma Blood plasma is a light amber-colored liquid component of blood in which blood cells are absent, but contains proteins and other constituents of whole blood in suspension. It makes up about 55% of the body's total blood volume. It is the intra ...

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 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 the physically separate mater ...

, 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 metabolism, by oxidation, of both xenobiotics, including drugs, and endogenous compounds, including fatty acids. In humans, the prote ...

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

carboxy In organic chemistry, a carboxylic acid is an organic acid that contains a carboxyl group () attached to an R-group. The general formula of a carboxylic acid is or , with R referring to the alkyl, alkenyl, aryl, or other group. Carboxylic ...

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 glucur ...

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 (also known as elimination half-life, pharmacologic half-life) is the time taken for concentration of a biological substance (such as a medication) to decrease from its maximum concentration ( Cmax) to half of Cmax in the bl ...

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 Flufenamic acid (FFA) is a member of the anthranilic acid derivatives (or fenamate) class of nonsteroidal anti-inflammatory drugs (NSAIDs). Like other members of the class, it is a cyclooxygenase (COX) inhibitor, preventing the formation of pr ...

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 ...

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.

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.

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 neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...

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.

References

Futher reading

* * * {{Ion channel modulators Nonsteroidal anti-inflammatory drugs Anthranilic acids GABAA receptor positive allosteric modulators