Acemetacin is a

non-steroidal 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 ...

(NSAID) used for the treatment of

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 ...

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 invol ...

, lower back pain, and relieving post-operative pain. It is manufactured by

Merck KGaA The Merck Group, branded and commonly known as Merck, is a German multinational science and technology company headquartered in Darmstadt, with about 60,000 employees and present in 66 countries. The group includes around 250 companies; the ma ...

under the tradename Emflex, and is available in the UK and other countries as a prescription-only drug.

Medical uses

Acemetacin has proven effective in the treatment of osteoarthritis, rheumatoid arthritis,

ankylosing spondylitis Ankylosing spondylitis (AS) is a type of arthritis characterized by long-term inflammation of the joints of the spine typically where the spine joins the pelvis. Occasionally areas affected may include other joints such as the shoulders or hi ...

, and other kinds of rheumatoid inflammation, as well as in post-operative and post-traumatic pain and attack of

gout Gout ( ) is a form of inflammatory arthritis characterized by recurrent attacks of a red, tender, hot and swollen joint, caused by deposition of monosodium urate monohydrate crystals. Pain typically comes on rapidly, reaching maximal intens ...

. Application of a single dose of acemetacin for post-operative pain is not well supported by studies.

Contraindications

Contraindications are basically the same as with other NSAIDs:

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 ...

reactions to NSAIDs in the past (typically asthma or skin reactions),

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 ...

or cerebral bleeding,

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 ...

haematopoietic Haematopoiesis (, from Greek , 'blood' and 'to make'; also hematopoiesis in American English; sometimes also h(a)emopoiesis) is the formation of blood cellular components. All cellular blood components are derived from haematopoietic stem cells. ...

disorders (

anaemia Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, t ...

leukopenia Leukopenia () is a decrease in the number of leukocytes (WBC). Found in the blood, they are the white blood cells, and are the body's primary defense against an infection. Thus the condition of leukopenia places individuals at increased risk of in ...

), and during the third trimester of pregnancy. on Emflex.

Adverse effects

Common side effects (in about 1–10% of patients) include gastrointestinal problems typical of NSAIDs, such as

nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...

, diarrhoea, stomach pain, and peptic ulcer; central nervous effects like headache and dizziness; and skin reactions. Gastrointestinal tolerability is better than that of the related drug

indometacin Indometacin, also known as indomethacin, is a nonsteroidal anti-inflammatory drug (NSAID) commonly used as a prescription medication to reduce fever, pain, stiffness, and swelling from inflammation. It works by inhibiting the production of pros ...

. Severe allergic reactions and haematopoietic disorders occur in fewer than 0.01% of patients.

Interactions

The following interactions, typical of NSAIDs, have been described: * other NSAIDs, corticosteroids: increased frequency of side effects, especially peptic ulcers and gastrointestinal bleeding *

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 i ...

s, ACE inhibitors and other antihypertensive drugs: reduced effectiveness of these drugs * with ACE inhibitors or ciclosporin, increased risk of kidney function disorders * anticoagulants such as warfarin: increased risk of bleeding * increased blood plasma concentrations of digoxin and methotrexate * decreased plasma concentrations of lithium (medication), lithium

Pharmacology

Acemetacin acts as an inhibitor of cyclooxygenase (COX), producing the anti-inflammatory and analgetic (pain relieving) effects. In the body, it is partly metabolized to indometacin, which also acts as a COX inhibitor. The same mechanism is responsible for the antipyretic and Antiplatelet drug, antiplatelet effects, which are however not clinically used, as well as for the typical NSAID adverse effects. An advantage of acemetacin is that it reduces gastric damage as compared to indometacin, possibly because acemetacin has less effect on the increase of leukotriene B4 synthesis and tumor necrosis factor (TNF) expression, leading to less induction of leukocyte-endothelial adherence.

Pharmacokinetics

The substance is quickly and almost completely absorbed from the gut. Highest blood plasma concentrations are reached after two hours. It is bound to plasma proteins to 80–90%. Concentrations in the synovial fluid and synovial membrane, membranes, muscle and bone are higher than in the blood. Apart from the active metabolite indometacin, a number of inactive metabolites are found after application of acemetacin: the O-desmethyl-, des-4-chlorobenzoyl-, and O-desmethyl-des-4-chlorobenzoyl derivatives of both indometacin and acemetacin, as well as all of these substances' glucuronides (mediated at least partly by the enzyme UGT2B7). Elimination half-life is 4.5±2.8 hours (in some individuals up to 16 hours) under steady state conditions. 40% are eliminated via the kidney, and 50% via the faeces.

Chemistry

Acemetacin is the glycolic acid ester of indometacin. It is a fine, slightly yellowish, crystalline powder that melts at . It is Polymorphism (materials science), polymorphic, with four known anhydrous (water-free) and two monohydrate crystalline forms.

Society and culture

Brand names

Other brand names include ''Zadex'' (Hungary), ''Rheutrop'' (Austria), ''Acemetadoc'', ''Acephlogont'', ''Azeat'', ''Rantudil'' (Germany, Hungary, Mexico, Poland, Portugal, Turkey), ''Gamespir'' (Greece), ''Oldan'', ''Reudol'' (Spain), ''Tilur'' (Switzerland), ''ACEO'' (Taiwan), ''Ost-map'' (Egypt).

References

{{Prostanoidergics Indoles Acetic acids Carboxamides Merck brands Indole ethers at the benzene ring Chloroarenes Prodrugs Nonsteroidal anti-inflammatory drugs