Meloxicam
Encyclopedia
Meloxicam is a nonsteroidal anti-inflammatory drug (NSAID) with analgesic
and fever reducer effects. It is a derivative of oxicam
, closely related to piroxicam
, and falls in the enolic acid group of NSAIDs. It was developed by Boehringer-Ingelheim
.
(COX), the enzyme
responsible for converting arachidonic acid
into prostaglandin H2
—the first step in the synthesis of prostaglandin
s, which are mediators of inflammation.
Meloxicam has been shown, especially at its low therapeutic dose, selectively to inhibit COX-2 over COX-1.
Meloxicam concentrations in synovial fluid
range from 40% to 50% of those in plasma. The free fraction in synovial fluid is 2.5 times higher than in plasma, due to the lower albumin content in synovial fluid as compared to plasma. The significance of this penetration is unknown, but it may account for the fact that it performs exceptionally well in treatment of arthritis in animal models.
, blinding headaches, rash, and very dark or black stool (a sign of intestinal bleeding). It has fewer gastrointestinal side effects than diclofenac
, piroxicam
, naproxen
, and perhaps all other NSAIDs which are not COX-2 selective. Although meloxicam does inhibit thromboxane
A, it does not appear to do so at levels that would interfere with platelet
function.
field, most commonly in dogs, but also sees off-label use
in other animals such as cattle, cats and exotics. The U.S. Food and Drug Administration
sent a Notice of Violation to the manufacturer for its promotional materials which included promotion of the drug for off-label use. In the U.S. the drug is indicated for management of pain and inflammation associated with osteoarthritis
in dogs only. In Europe, where the product has been available since the early 1990s, it is also prescribed and licensed for other anti-inflammatory benefits including relief from both acute and chronic pain
in dogs. Side effects in animals are similar to those found in humans; the principal side effect is gastrointestinal irritation (vomiting, diarrhea and ulceration
). Rarer but important side effects include liver and kidney toxicity.
Since 2003, the oral (liquid
) formulations of meloxicam have been licensed in the U.S for use in dogs only, with the January 2005 product insert specifically warning in bold-face type: "Do not use in cats." An injectable formulation for use in dogs was approved by the FDA November 2003, with a formulation for cats, for surgical use only, approved in October, 2004.
In the U.S., per the manufacturer's clinical instructions as of July 2010, injectable meloxicam is indicated in operative use with felines as a single, one-time dose only, with specific and repeated warnings not to administer a second dose. In June 2007, a new oral version of meloxicam was licensed in Europe
for the long-term relief of pain in cats. As of June 2008, meloxicam is registered for long term use in cats in Australia, New Zealand, and throughout Europe.
In Europe, meloxicam is marketed under the brand names Movalis, Melox, and Recoxa. In the UK, U.S., Middle East, Argentina, Paraguay, Uruguay and Australia it is marketed under the brand name Mobic, in Germany as Mobec, and in Canada as Mobicox. In Latin America, the drug is marketed as Tenaron, Ilacox, Mavicam, Melocam, or Artriflam. A veterinary
formulation of the drug is marketed as Metacam, Meloxidyl, Meloxoral, Meloxidolor or Petcam. In the Philippines, it is generally marketed under the brand name Moxen. In Greece
, it is manufactured under licence from aVianex S.A under the name Loxitan.
Analgesic
An analgesic is any member of the group of drugs used to relieve pain . The word analgesic derives from Greek an- and algos ....
and fever reducer effects. It is a derivative of oxicam
Oxicam
Oxicam are members of a class of non-steroidal anti-inflammatory drugs that bind closely to plasma proteins. Most oxicams are unselective inhibitors of the cyclooxygenase enzymes...
, closely related to piroxicam
Piroxicam
Piroxicam is a non-steroidal anti-inflammatory drug of the oxicam class used to relieve the symptoms of rheumatoid and osteoarthritis, primary dysmenorrhoea, postoperative pain; and act as an analgesic, especially where there is an inflammatory component...
, and falls in the enolic acid group of NSAIDs. It was developed by Boehringer-Ingelheim
Boehringer-Ingelheim
C.H. Boehringer Sohn AG & Ko. KG is the parent company of Boehringer Ingelheim, which was founded in 1885 by Albert Boehringer in Ingelheim am Rhein. The Boehringer Ingelheim group is one of the world's 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally...
.
Mechanism of action
Meloxicam inhibits cyclooxygenaseCyclooxygenase
Cyclooxygenase is an enzyme that is responsible for formation of important biological mediators called prostanoids, including prostaglandins, prostacyclin and thromboxane. Pharmacological inhibition of COX can provide relief from the symptoms of inflammation and pain...
(COX), the enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
responsible for converting arachidonic acid
Arachidonic acid
Arachidonic acid is a polyunsaturated omega-6 fatty acid 20:4.It is the counterpart to the saturated arachidic acid found in peanut oil, Arachidonic acid (AA, sometimes ARA) is a polyunsaturated omega-6 fatty acid 20:4(ω-6).It is the counterpart to the saturated arachidic acid found in peanut oil,...
into prostaglandin H2
Prostaglandin H2
Prostaglandin H2 is a type of Prostaglandin which is derived from arachidonic acid and is a precursor for many other biologically significant molecules.It is acted upon by:* prostacyclin synthase to create prostacyclin...
—the first step in the synthesis of prostaglandin
Prostaglandin
A prostaglandin is any member of a group of lipid compounds that are derived enzymatically from fatty acids and have important functions in the animal body. Every prostaglandin contains 20 carbon atoms, including a 5-carbon ring....
s, which are mediators of inflammation.
Meloxicam has been shown, especially at its low therapeutic dose, selectively to inhibit COX-2 over COX-1.
Meloxicam concentrations in synovial fluid
Synovial fluid
Synovial fluid is a viscous, non-Newtonian fluid found in the cavities of synovial joints. With its yolk-like consistency , the principal role of synovial fluid is to reduce friction between the articular cartilage of synovial joints during movement.-Overview:The inner membrane of synovial joints...
range from 40% to 50% of those in plasma. The free fraction in synovial fluid is 2.5 times higher than in plasma, due to the lower albumin content in synovial fluid as compared to plasma. The significance of this penetration is unknown, but it may account for the fact that it performs exceptionally well in treatment of arthritis in animal models.
Adverse effects
Meloxicam use can result in gastrointestinal toxicity and bleeding, tinnitusTinnitus
Tinnitus |ringing]]") is the perception of sound within the human ear in the absence of corresponding external sound.Tinnitus is not a disease, but a symptom that can result from a wide range of underlying causes: abnormally loud sounds in the ear canal for even the briefest period , ear...
, blinding headaches, rash, and very dark or black stool (a sign of intestinal bleeding). It has fewer gastrointestinal side effects than diclofenac
Diclofenac
Diclofenac is a non-steroidal anti-inflammatory drug taken to reduce inflammation and as an analgesic reducing pain in certain conditions....
, piroxicam
Piroxicam
Piroxicam is a non-steroidal anti-inflammatory drug of the oxicam class used to relieve the symptoms of rheumatoid and osteoarthritis, primary dysmenorrhoea, postoperative pain; and act as an analgesic, especially where there is an inflammatory component...
, naproxen
Naproxen
Naproxen sodium is a nonsteroidal anti-inflammatory drug commonly used for the reduction of pain, fever, inflammation and stiffness caused by conditions such as:...
, and perhaps all other NSAIDs which are not COX-2 selective. Although meloxicam does inhibit thromboxane
Thromboxane
Thromboxane is a member of the family of lipids known as eicosanoids. The two major thromboxanes are thromboxane A2 and thromboxane B2. The distinguishing feature of thromboxanes is a 6-membered ether-containing ring....
A, it does not appear to do so at levels that would interfere with platelet
Platelet
Platelets, or thrombocytes , are small,irregularly shaped clear cell fragments , 2–3 µm in diameter, which are derived from fragmentation of precursor megakaryocytes. The average lifespan of a platelet is normally just 5 to 9 days...
function.
Veterinary use
Meloxicam is also used in the veterinaryVeterinary medicine
Veterinary Medicine is the branch of science that deals with the prevention, diagnosis and treatment of disease, disorder and injury in non-human animals...
field, most commonly in dogs, but also sees off-label use
Off-label use
Off-label use is the practice of prescribing pharmaceuticals for an unapproved indication or in an unapproved age group, unapproved dose or unapproved form of administration...
in other animals such as cattle, cats and exotics. The U.S. Food and Drug Administration
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
sent a Notice of Violation to the manufacturer for its promotional materials which included promotion of the drug for off-label use. In the U.S. the drug is indicated for management of pain and inflammation associated with osteoarthritis
Osteoarthritis
Osteoarthritis also known as degenerative arthritis or degenerative joint disease, is a group of mechanical abnormalities involving degradation of joints, including articular cartilage and subchondral bone. Symptoms may include joint pain, tenderness, stiffness, locking, and sometimes an effusion...
in dogs only. In Europe, where the product has been available since the early 1990s, it is also prescribed and licensed for other anti-inflammatory benefits including relief from both acute and chronic pain
Chronic pain
Chronic pain has several different meanings in medicine. Traditionally, the distinction between acute and chronic pain has relied upon an arbitrary interval of time from onset; the two most commonly used markers being 3 months and 6 months since the initiation of pain, though some theorists and...
in dogs. Side effects in animals are similar to those found in humans; the principal side effect is gastrointestinal irritation (vomiting, diarrhea and ulceration
Peptic ulcer
A peptic ulcer, also known as PUD or peptic ulcer disease, is the most common ulcer of an area of the gastrointestinal tract that is usually acidic and thus extremely painful. It is defined as mucosal erosions equal to or greater than 0.5 cm...
). Rarer but important side effects include liver and kidney toxicity.
Since 2003, the oral (liquid
Suspension (chemistry)
In chemistry, a suspension is a heterogeneous fluid containing solid particles that are sufficiently large for sedimentation. Usually they must be larger than 1 micrometer. The internal phase is dispersed throughout the external phase through mechanical agitation, with the use of certain...
) formulations of meloxicam have been licensed in the U.S for use in dogs only, with the January 2005 product insert specifically warning in bold-face type: "Do not use in cats." An injectable formulation for use in dogs was approved by the FDA November 2003, with a formulation for cats, for surgical use only, approved in October, 2004.
In the U.S., per the manufacturer's clinical instructions as of July 2010, injectable meloxicam is indicated in operative use with felines as a single, one-time dose only, with specific and repeated warnings not to administer a second dose. In June 2007, a new oral version of meloxicam was licensed in Europe
Europe
Europe is, by convention, one of the world's seven continents. Comprising the westernmost peninsula of Eurasia, Europe is generally 'divided' from Asia to its east by the watershed divides of the Ural and Caucasus Mountains, the Ural River, the Caspian and Black Seas, and the waterways connecting...
for the long-term relief of pain in cats. As of June 2008, meloxicam is registered for long term use in cats in Australia, New Zealand, and throughout Europe.
Consumer confidence
As issues arise with any drug used off-label, the off-label use of meloxicam in cats has led to many reports of irreversible renal damage and death. A peer-reviewed journal article cites feline overdose of NSAIDs, including meloxicam, as being a cause of severe kidney damage in cats.Brands
Veterinary medicine
Veterinary Medicine is the branch of science that deals with the prevention, diagnosis and treatment of disease, disorder and injury in non-human animals...
formulation of the drug is marketed as Metacam, Meloxidyl, Meloxoral, Meloxidolor or Petcam. In the Philippines, it is generally marketed under the brand name Moxen. In Greece
Greece
Greece , officially the Hellenic Republic , and historically Hellas or the Republic of Greece in English, is a country in southeastern Europe....
, it is manufactured under licence from aVianex S.A under the name Loxitan.