Meloxicam

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Meloxicam
Meloxicam2DACS.svg
Systematic (IUPAC) name
4-hydroxy-2-methyl-N-(5-methyl-2-thiazolyl)-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide.
Clinical data
Trade namesMobic
AHFS/Drugs.commonograph
MedlinePlusa601242
Pregnancy cat.
Legal status
RoutesOral
Pharmacokinetic data
Bioavailability89%[1]
Protein binding99.4%[1]
MetabolismHepatic (CYP2C9 and 3A4-mediated)[1]
Half-life20 hours[1]
ExcretionUrine and faeces equally[1]
Identifiers
CAS number71125-38-7 YesY
ATC codeM01AC06
PubChemCID 5281106
DrugBankDB00814
ChemSpider10442740 YesY
UNIIVG2QF83CGL YesY
KEGGD00969 YesY
ChEBICHEBI:6741 N
ChEMBLCHEMBL599 YesY
PDB ligand IDMXM (PDBe, RCSB PDB)
Chemical data
FormulaC14H13N3O4S2 
Mol. mass351.403 g/mol
 N (what is this?)  (verify)
 
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Meloxicam
Meloxicam2DACS.svg
Systematic (IUPAC) name
4-hydroxy-2-methyl-N-(5-methyl-2-thiazolyl)-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide.
Clinical data
Trade namesMobic
AHFS/Drugs.commonograph
MedlinePlusa601242
Pregnancy cat.
Legal status
RoutesOral
Pharmacokinetic data
Bioavailability89%[1]
Protein binding99.4%[1]
MetabolismHepatic (CYP2C9 and 3A4-mediated)[1]
Half-life20 hours[1]
ExcretionUrine and faeces equally[1]
Identifiers
CAS number71125-38-7 YesY
ATC codeM01AC06
PubChemCID 5281106
DrugBankDB00814
ChemSpider10442740 YesY
UNIIVG2QF83CGL YesY
KEGGD00969 YesY
ChEBICHEBI:6741 N
ChEMBLCHEMBL599 YesY
PDB ligand IDMXM (PDBe, RCSB PDB)
Chemical data
FormulaC14H13N3O4S2 
Mol. mass351.403 g/mol
 N (what is this?)  (verify)

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.[2] It was developed by Boehringer-Ingelheim. Meloxicam starts to relieve pain about 30–60 minutes after administration.[3]

Mechanism of action[edit]

Meloxicam inhibits cyclooxygenase (COX), the enzyme responsible for converting arachidonic acid into prostaglandin H2—the first step in the synthesis of prostaglandins, which are mediators of inflammation. Meloxicam has been shown, especially at its low therapeutic doses, selectively to inhibit COX-2 over COX-1.[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,[2] but it may account for the fact that it performs exceptionally well in treatment of arthritis in animal models.[4]

Side effects[edit]

Meloxicam use can result in gastrointestinal toxicity and bleeding, tinnitus, blinding headaches, rash, and very dark or black stool (a sign of intestinal bleeding). It has fewer gastrointestinal side effects than diclofenac,[5] piroxicam,[6] naproxen,[7] and perhaps all other NSAIDs which are not COX-2 selective.[5] Although meloxicam does inhibit thromboxane A, it does not appear to do so at levels that would interfere with platelet function. A pooled analysis of randomized, controlled studies of meloxicam therapy of up to 60 days duration found that meloxicam was associated with a statistically significantly lower number of thromboembolic complications than the NSAID diclofenac (0.2% verses 0.8% respectively) but a similar incidence of thromboembolic events to naproxen and piroxicam .[8]

Potential serious cardiovascular side effects[edit]

Meloxicam is known to cause sudden high blood pressure, angina, myocardial infarction, stroke and death. Persons with hypertension, high cholesterol, or diabetes are at risk for cardiovascular side effects. Persons with family history of heart disease, heart attack or stroke must tell their treating physician as the potential for serious cardiovascular side effects is significant.Medline PlusDrugs.com

Veterinary use[edit]

Meloxicam is also used in the veterinary field, most commonly in dogs and cats, but also sees off-label use in other animals such as cattle and exotics.[9][10] 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.[11] 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,[citation needed] 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,[12] with the January 2005 product insert specifically warning in bold-face type: "Do not use in cats."[13] An injectable formulation for use in dogs was approved by the FDA in November 2003,[14] with a formulation for cats, for surgical use only, approved in October 2004.[15]

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.[16] 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.

Safety hazards[edit]

The off-label use of meloxicam in cats has led to many reports of irreversible renal damage and death.[17] A peer-reviewed journal article cites feline overdose of NSAIDs, including meloxicam, as being a cause of severe kidney damage in cats.[18]

References[edit]

  1. ^ a b c d e f Noble, S; Balfour, JA (March 1996). "Meloxicam.". Drugs 51 (3): 424–30; discussion 431–32. doi:10.2165/00003495-199651030-00007. PMID 8882380. 
  2. ^ a b "Meloxicam official FDA information, side effects, and uses". Drugs.com. March 2010. Retrieved 17 March 2010. 
  3. ^ Auvinet, B; Ziller, R; Appelboom, T; Velicitat, P (November–December 1995). "Comparison of the onset and intensity of action of intramuscular meloxicam and oral meloxicam in patients with acute sciatica.". Clinical Therapeutics 17 (6): 1078–98. doi:10.1016/0149-2918(95)80086-7. PMID 8750399. 
  4. ^ Engelhardt, G; Homma, D; Schlegel, K; Utzmann, R; Schnitzler, C (Oct 1995). "Anti-inflammatory, analgesic, antipyretic and related properties of meloxicam, a new non-steroidal anti-inflammatory agent with favourable gastrointestinal tolerance". Inflammation Research 44 (10): 423–433. doi:10.1007/BF01757699. PMID 8564518. 
  5. ^ a b Hawkey, C; Kahan, A; Steinbrü, K; Alegre, C; Baumelou, E; Bégaud, B; Dequeker, J; Isomäki, H et al. (Sep 1998). "Gastrointestinal tolerability of meloxicam compared to diclofenac in osteoarthritis patients". Rheumatology 37 (9): 937–945(9). doi:10.1093/rheumatology/37.9.937. 
  6. ^ Dequeker, J; Hawkey, C; Kahan, A; Steinbruck, K; Alegre, C; Baumelou, E; Begaud, B; Isomaki, H et al. (1998). "Improvement in gastrointestinal tolerability of the selective cyclooxygenase (COX)-2 inhibitor, meloxicam, compared with piroxicam: results of the Safety and Efficacy Large-scale Evaluation of COX- inhibiting Therapies (SELECT) trial in osteoarthritis". The British Journal of Rheumatology 37 (9): 946–51. doi:10.1093/rheumatology/37.9.946. PMID 9783758. 
  7. ^ Wojtulewski, JA; Schattenkirchner, M; Barceló, P; Le Loët, X; Bevis, PJR; Bluhmki, E; Distel, M. "A Six-Month Double-Blind Trial to Compare the Efficacy and Safety of Meloxicam 7.5 mg Daily and Naproxen 750 mg Daily in Patients with Rheumatoid Arthritis". Rheumatology. 35, Supplement 1: 22–8. 
  8. ^ Singh, G; Lanes, S; Steinbrü, G; Triadafilopoulos (2004). "Gastrointestinal tolerability of meloxicam compared to diclofenac in osteoarthritis patients". Am J Med 117 (9): 100–6. doi:10.1016/j.amjmed.2004.03.012. PMID 15234645. 
  9. ^ Off-label use discussed in: Arnold Plotnick MS, DVM, ACVIM, ABVP, Pain Management using Metacam, and Stein, Robert, Perioperative Pain Managemment Part IV, Looking Beyond Butorphanol, Sep 2006.
  10. ^ For off-label use example in rabbits, see Krempels, Dana, Hind Limb Paresis and Paralysis in Rabbits, University of Miami Biology Department.
  11. ^ US FDA Notice of Violation for off-label use promotion, April 2005.
  12. ^ "NADA 141-213: New Animal Drug Application Approval (for Metacam (meloxicam) 0.5 mg/mL and 1.5 mg/mL Oral Suspension)". US Food and Drug Administration. April 15, 2003. Retrieved 24 July 2010. 
  13. ^ Metacam Client Information Sheet, product description: "Non-steroidal anti-inflammatory drug for oral use in dogs only", and in the "What Is Metacam" section in bold-face type: "Do not use in cats.", January 2005.
  14. ^ Metacam 5 mg/mL Solution for Injection
  15. ^ Metacam 5 mg/mL Solution for Injection, Supplemental Approval October 28, 2004.
  16. ^ See the manufacturer's FAQ on its website, and its clinical dosing instructions for cats.
  17. ^ Discussion of Metacam use at persiancats.org in Metacam Risks In Cats, and at the consumer site metacamkills.com.
  18. ^ Merola, Valentina, DVM, DABT, and Dunayer Eric, MS, VMD, DABT, The 10 most common toxicoses in cats, Toxicology Brief, Veterinary Medicine, pp. 340–342, June, 2006.

External links[edit]