Meloxicam

Source: Wikipedia, the free encyclopedia.

Meloxicam
Clinical data
Trade namesMobic, Metacam, Anjeso, others
AHFS/Drugs.comMonograph
MedlinePlusa601242
License data
Pregnancy
category
intravenous
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability89%[6]
Protein binding99.4%[6]
MetabolismLiver (CYP2C9 and 3A4-mediated)[6]
Elimination half-life20 hours[6]
ExcretionUrine and feces equally[6]
Identifiers
  • 4-Hydroxy-2-methyl-N-(5-methyl-2-thiazolyl)-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide
JSmol)
  • Cc1cnc(s1)NC(=O)C\3=C(/O)c2ccccc2S(=O)(=O)N/3C
  • InChI=1S/C14H13N3O4S2/c1-8-7-15-14(22-8)16-13(19)11-12(18)9-5-3-4-6-10(9)23(20,21)17(11)2/h3-7,18H,1-2H3,(H,15,16,19) checkY
  • Key:ZRVUJXDFFKFLMG-UHFFFAOYSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Meloxicam, sold under the brand name Mobic among others, is a

injection into a vein.[8][9] It is recommended that it be used for as short a period as possible and at a low dose.[8]

Common side effects include abdominal pain, dizziness, swelling, headache, and a rash.

third trimester of pregnancy.[8] It blocks cyclooxygenase-2 (COX-2) more than it blocks cyclooxygenase-1 (COX-1).[8] It is in the oxicam family of chemicals and is closely related to piroxicam.[8]

Meloxicam was patented in 1977 and approved for medical use in the United States in 2000.

generic medication.[8] In 2021, it was the 32nd most commonly prescribed medication in the United States, with more than 18 million prescriptions.[11][12] An intravenous version of meloxicam (Anjeso) was approved for medical use in the United States in February 2020.[13][9]

Adverse effects

See also: Nonsteroidal anti-inflammatory drug

Meloxicam use can result in

gastrointestinal toxicity and bleeding, headaches, rash, and very dark or black stool (a sign of intestinal bleeding). It has fewer gastrointestinal side effects than diclofenac,[14] piroxicam,[15] naproxen,[16] and perhaps all other NSAIDs which are not COX-2 selective.[14]

In October 2020, the U.S. Food and Drug Administration (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.[17][18] They recommend avoiding NSAIDs in pregnant women at 20 weeks or later in pregnancy.[17][18]

Cardiovascular

Like other

heart attack and stroke.[19] Although meloxicam inhibits formation of thromboxane A, it does not appear to do so at levels that would interfere with platelet function.[20][21] 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% versus 0.8% respectively) but a similar incidence of thromboembolic events to naproxen and piroxicam.[22]

People with hypertension, high cholesterol, or diabetes are at risk for cardiovascular side effects. People with family history of heart disease, heart attack, or stroke should tell their treating physician as the potential for serious cardiovascular side effects is significant.[23][24]

Gastrointestinal

NSAIDs cause an increase in the risk of serious gastrointestinal adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. Elderly patients are at greater risk for serious gastrointestinal events.[25]

Mouth

It is recommended to withhold meloxicam use for at least four to six half-lives prior to surgical or dental procedures due to increased risk for

ulcerative stomatitis and dry mouth.[medical citation needed
]

Mechanism of action

Main article:
Non-steroidal anti-inflammatory drug

Meloxicam blocks 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 low

COX-1.[6]

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,[25] but it may account for the fact that it performs exceptionally well in treatment of arthritis in animal models.[26]

Pharmacokinetics

Absorption

The

bioequivalent.[8] Use of oral meloxicam following a high-fat breakfast increases the mean peak drug levels by about 22%; however, the manufacturer does not make any specific meal recommendations. In addition, the use of antacids does not show pharmacokinetic interactions.[4] With chronic dosing, the time to maximum plasma concentration following oral administration is approximately 5–6 hours.[27]

Distribution

The mean volume of distribution of meloxicam is approximately 10 L. It is highly protein-bound, mainly to albumin.[21][27]

Metabolism

Meloxicam is extensively metabolized in the liver by the enzymes CYP2C9 and CYP3A4 (minor) into four inactive metabolites. Peroxidase activity is thought to be responsible for the other two remaining metabolites.[4][28]

Excretion

Meloxicam is predominantly excreted in the form of metabolites and occurs to equal extents in the urine and feces.[4] Traces of unchanged parent drug are found in urine and feces.[4] The mean elimination half-life ranges from 15 to 20 hours.[4]

Specific populations

Geriatrics

Use of meloxicam is not recommended in people with peptic ulcer disease or increased gastrointestinal bleed risk, including those over 75 years of age or those taking medications associated with bleeding risk.[29] Adverse events have been found to be dose-dependent and associated with length of treatment.[29][4]

Veterinary use

Meloxicam is used in veterinary medicine to treat dogs,[30][31] but also sees off-label use in other animals such as cattle and exotics.[32][33]

The most common side effects include gastrointestinal irritation (vomiting, diarrhea, and

ulceration).[30]

In healthy dogs given meloxicam, no perioperative adverse effects on the cardiovascular system have been reported at recommended dosages.[34] Perioperative administration of meloxicam to cats did not affect postoperative respiratory rate nor heart rate.[35]

Meloxicam has been investigated as an alternative to diclofenac by the Royal Society for the Protection of Birds (RSPB) to prevent deaths of vultures.[36]

The Use of Meloxicam in Cats

The issue of using meloxicam in cats involves conflicting guidelines, differing legislation, and a narrow therapeutic safety margin that can easily turn the drug from cure to poison. More specifically:

The

acute renal failure and death and has added the following boxed warning to the products' label: "Repeated use of meloxicam in cats has been associated with acute renal failure and death. Do not administer additional injectable or oral meloxicam to cats. See Contraindications, Warnings, and Precautions for detailed information."[39] In contrast, in the European Union and other continents or countries, the use of the drug in cats is allowed.[40][41]

Another conflicting guideline concerns a specific meloxicam oral suspension product for cats. Its instruction sheet states that: "Typical adverse reactions of

NSAIDs such as loss of appetite, vomiting, diarrhoea, faecal occult blood, apathy and renal failure have occasionally been reported. These side effects are in most cases transient and disappear following termination of the treatment but in very rare cases may be serious or fatal."[42] However, the main page of the official website of the same meloxicam product states: "Important Safety Information: DO NOT USE [...] ORAL SUSPENSION IN CATS. Acute renal failure and death have been associated with the use of meloxicam in cats."[43]

The data sheets for meloxicam products for cats also state that: "Meloxicam has a narrow therapeutic safety margin in cats and clinical signs of overdose may be seen at relatively small overdose levels."[42] The dosage policy for meloxicam oral suspension products for cats as described in the data sheets defines the amount administered as proportional to body weight. There is no separate dosage guideline for overweight or obese cats. This is worth mentioning on the one hand because the article Drug dosing in obese adults[44] advocates that the use of total body weight in obese adults may lead to drug toxicity and suggests individualised dosing based on the patient's ideal rather than actual body weight, and, on the other hand, precisely because the range safety of meloxicam for cats is so limited.

Some additional information about giving meloxicam to cats from researchers is as follows: A peer-reviewed journal article cites NSAIDs, including meloxicam, as causing gastrointestinal upset and, at high doses, acute kidney injury and CNS signs such as seizures and comas in cats. It adds that cats have a low tolerance for NSAIDs.[45][46] Also, in another scientific journal there is talk of research according to which cats that received meloxicam had greater proteinuria at 6 months than cats that received placebo. It was concluded that meloxicam should be used with caution in cats with chronic kidney disease.[47]

Pharmacokinetics

In dogs, the

absorption of meloxicam from the stomach is not affected by the presence of food,[48] with the peak concentration (Cmax) of meloxicam occurring in the blood 7–8 hours after administration.[48] The half-life of meloxicam is approximately 24 hours in dogs.[48]

In the koala (Phascolarctos cinereus), very little meloxicam is absorbed into the blood after oral administration (that is, it has poor bioavailability).[49]

Legal status

United States

In 2003, meloxicam was approved in the U.S. for use in dogs for the management of pain and inflammation associated with

injectable formulation for use in dogs was approved by the U.S. Food and Drug Administration (FDA) in November 2003.[52]

In October 2004, a formulation for use in cats was approved for use prior to surgery only.[53] This is an injectable meloxicam, indicated for as a single, one-time dose only, with specific and repeated warnings not to administer a second dose.[54]

In 2005, the FDA sent a Notice of Violation to the manufacturer for its promotional materials which included promotion of the drug for off-label use.[55]

In February 2020, meloxicam injection was approved for use in the United States. The FDA granted the approval of Anjeso to Baudax Bio.[9][56]

European Union

In Europe the product is licensed for other anti-inflammatory benefits including relief from both

musculoskeletal disorders.[57]

Meloxicam was authorised for use in cattle throughout the European Union in January 1998, via a centralised marketing authorisation.[58] The first generic meloxicam product was approved in 2006.[58]

Other countries

As of June 2008, meloxicam is registered for long-term use in cats in Australia, New Zealand, and Canada.[59] In the United Kingdom, meloxicam is licensed for use in cats, guinea pigs, horses, and livestock including pigs and cattle. [60]

See also

References

  1. ^ Use During Pregnancy and Breastfeeding
  2. FDA
    . Retrieved 22 October 2023.
  3. ^ "Health product highlights 2021: Annexes of products approved in 2021". Health Canada. 3 August 2022. Retrieved 25 March 2024.
  4. ^ a b c d e f g "Mobic- meloxicam tablet". DailyMed. Retrieved 15 May 2021.
  5. ^ "Anjeso- meloxicam injection". DailyMed. Retrieved 15 May 2021.
  6. ^
    S2CID 260452199
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  7. ISBN 9780857113382
    .
  8. ^ a b c d e f g h i j k "Meloxicam Monograph for Professionals". Drugs.com. AHFS. Archived from the original on 23 December 2018. Retrieved 23 December 2018.
  9. ^ a b c "Baudax Bio Announces FDA Approval of Anjeso for the Management of Moderate to Severe Pain". Baudax Bio, Inc. (Press release). 20 February 2020. Archived from the original on 21 February 2020. Retrieved 20 February 2020.
  10. ISBN 9783527607495. Archived
    from the original on 10 July 2020. Retrieved 30 June 2020.
  11. ^ "The Top 300 of 2021". ClinCalc. Archived from the original on 15 January 2024. Retrieved 14 January 2024.
  12. ^ "Meloxicam - Drug Usage Statistics". ClinCalc. Retrieved 14 January 2024.
  13. ^ "Anjeso- meloxicam injection". DailyMed. 22 February 2022. Retrieved 8 October 2022.
  14. ^
    PMID 9783757
    .
  15. PMID 9783758
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  16. PMID 8630632
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  17. ^ a b "FDA Warns that Using a Type of Pain and Fever Medication in Second Half of Pregnancy Could Lead to Complications". U.S. Food and Drug Administration (FDA) (Press release). 15 October 2020. Retrieved 15 October 2020. Public Domain This article incorporates text from this source, which is in the public domain.
  18. ^ a b "NSAIDs may cause rare kidney problems in unborn babies". U.S. Food and Drug Administration. 21 July 2017. Retrieved 15 October 2020. Public Domain This article incorporates text from this source, which is in the public domain.
  19. PMID 2012
    .
  20. S2CID 205715393
    .
  21. ^
    S2CID 25512189
    . Meloxicam is extensively bound to plasma proteins (99.4%), primarily to albumin. Meloxicam has an apparent volume of distribution (Vd) 10 – 15 L in humans (0.1 – 0.2 L/kg) after oral administration and a mean volume of distribution at steady-state of 0.2 L/kg after intravenous administration."
    "None of the meloxicam treatment groups demonstrated inhibition of platelet aggregation to either arachidonic acid (AC) or adenosine diphosphate (ADP). However, there were no significant changes in the platelet count, prothrombin and activated partial thromboplastin time in any of the meloxicam and indomethacin groups. Other crossover studies also confirmed that meloxicam 15 mg/day caused a major reduction of maximum thromboxane production, but no reduction in collagen- or AC-induced platelet aggregation.
  22. PMID 15234645
    .
  23. ^ "Meloxicam". MedlinePlus. Archived from the original on 29 November 2014. Retrieved 15 November 2014.
  24. ^ "Meloxicam". Drugs.com. Archived from the original on 16 November 2014. Retrieved 15 November 2014.
  25. ^ a b "Meloxicam official FDA information, side effects, and uses". Drugs.com. March 2010. Archived from the original on 16 March 2010. Retrieved 17 March 2010.
  26. S2CID 37937305
    .
  27. ^
    PMID 30774225
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  28. ^ "Meloxicam (Professional Patient Advice)". Drugs.com. Archived from the original on 6 August 2019. Retrieved 6 August 2019.
  29. ^
    S2CID 59338182
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  30. ^ a b "Metacam- meloxicam suspension". DailyMed. Retrieved 15 May 2021.
  31. ^ "Metacam- meloxicam injection, solution". DailyMed. Retrieved 15 May 2021.
  32. ^ Off-label use discussed in: Arnold Plotnick MS, DVM, ACVIM, ABVP, Pain Management using Metacam Archived 14 July 2011 at the Wayback Machine, and Stein, Robert, Perioperative Pain Management Archived 18 April 2010 at the Wayback Machine Part IV, Looking Beyond Butorphanol, Sep 2006, Veterinary Anesthesia & Analgesia Support Group.
  33. ^ For off-label use example in rabbits, see Krempels, Dana, Hind Limb Paresis and Paralysis in Rabbits Archived 17 June 2010 at the Wayback Machine, University of Miami Biology Department.
  34. PMID 16412133
    .
  35. S2CID 30649716
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  36. PMID 16435886
    .
  37. ^ Medicine Cf (29 September 2022). "Get the Facts about Pain Relievers for Pets". FDA.
  38. ^ Medicine Cf (15 August 2023). "What Veterinarians Should Advise Clients About Pain Control and Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) in Dogs and Cats". FDA.
  39. ^ Medicine Cf (14 August 2023). "Information about the Boxed Warning on Meloxicam Labels regarding Safety Risks in Cats". FDA.
  40. ^ "Metacam | European Medicines Agency". www.ema.europa.eu. Retrieved 29 March 2024.
  41. ^ "Cats: Meloxicam Question for Department for Environment, Food and Rural Affairs". UK Parliament Written questions, answers and statements.
  42. ^ a b "Clinical particulars - Meloxidyl® 0.5 mg/ml oral suspension for cats". www.noahcompendium.co.uk. Retrieved 29 March 2024.
  43. ^ "Meloxidyl® from Ceva Animal Health". Retrieved 29 March 2024.
  44. PMID 29109603
    .
  45. ^ "Toxicology Brief: The 10 most common toxicoses in cats". Dvm360. 1 June 2006. Archived from the original on 29 August 2018. Retrieved 16 September 2018.
  46. ^ Merola V, Dunayer E (June 2006). "The 10 most common toxicoses in cats" (PDF). Veterinary Medicine: 340–342. Archived (PDF) from the original on 9 August 2019. Retrieved 9 August 2019.
  47. S2CID 220256059
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  48. ^
    PMID 22381180
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  49. PMID 23406022
    .
  50. ^ "NADA 141-213: New Animal Drug Application Approval (for Metacam (meloxicam) 0.5 mg/mL and 1.5 mg/mL Oral Suspension)" (PDF). Food and Drug Administration (FDA). 15 April 2003. Archived from the original (PDF) on 6 April 2017. Retrieved 24 July 2010.
  51. ^ "Client Information Sheet For Metacam (meloxicam) 1.5 mg/mL Oral Suspension" (PDF). Food and Drug Administration (FDA). January 2005. Archived from the original (PDF) on 15 November 2017. Metacam is a prescription non-steroidal anti-inflammatory drug (NSAID) that is used to control pain and inflammation (soreness) due to osteoarthritis in dogs. Osteoarthritis (OA) is a painful condition caused by "wear and tear" of cartilage and other parts of the joints that may result in the following changes or signs in your dog: Limping or lameness, decreased activity or exercise (reluctance to stand, climb stairs, jump or run, or difficulty in performing these activities), stiffness or decreased movement of joints. Metacam is given to dogs by mouth. Do not use Metacam Oral Suspension in cats. Acute kidney injury and death have been associated with the use of meloxicam in cats.
  52. ^ "NADA 141-219: Metacam (meloxicam) 5 mg/mL Solution for Injection" (PDF). U.S. Food and Drug Administration (FDA). 12 November 2003. Archived from the original (PDF) on 15 November 2017. Retrieved 8 August 2019.
  53. ^ "Metacam 5 mg/mL Solution for Injection, Supplemental Approval" (PDF). U.S. Food and Drug Administration (FDA). 28 October 2004. Archived from the original (PDF) on 15 November 2017. Retrieved 8 August 2019.
  54. ^ See the manufacturer's FAQ Archived 2 July 2011 at the Wayback Machine on its website, and its clinical dosing instructions for cats. Archived 6 September 2008 at the Wayback Machine
  55. ^ "Notice of Violation" (PDF). U.S. Food and Drug Administration (FDA). 19 April 2005. Archived from the original (PDF) on 13 January 2017. Retrieved 8 August 2019.
  56. ^ "Anjeso (meloxicam) injection, for intravenous use" (PDF). U.S. Food and Drug Administration (FDA). February 2020. Archived (PDF) from the original on 22 February 2020. Retrieved 21 February 2020.
  57. ISBN 9780702028588
    .
  58. ^ a b Wright E (March 2007). "Generic and biosimilar medicinal products in the European Union" (PDF). Chemistry Today. 25 (2): 4–6. Archived (PDF) from the original on 28 January 2020. Retrieved 28 January 2020.
  59. ISBN 9781482226065. Archived
    from the original on 1 September 2020. Retrieved 28 January 2020.
  60. ^ "Product Information Database". Veterinary Medicines Directorate. DEFRA. Retrieved 29 March 2023.
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