Amtolmetin

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Amtolmetin

Amtolmetin guacyl is a NSAID which is a non-acidic prodrug of tolmetin sodium and is used for the treatment of rheumatoid arthritis, osteoarthritis and juvenile rheumatoid arthritis. Apart from the NSAID specific properties of tolmetin, amtolmetin guacyl has additional antipyretic, analgesic and gastro-protective properties.

Indications

  • Rheumatoid arthritis
  • Osteoarthritis
  • Ankylosing spondylitis
  • Articular syndrome
  • Gout exacerbations
  • Bursitis
  • Headache
  • Tenosynovitis
  • Mild to moderate  intensity pain ( arthralgia, myalgia, neuralgia, migraine, toothache and headache, tuberculosis, anguish with injuries, burns)

Pharamcological Action

Amtolmetin stimulates capsaicin receptors present on gastro intestinal walls because of presence of vanillic moiety and also releases nitrogen oxide which is gastro-protective. It also inhibits prostaglandin synthesis and cyclooxygenase (COX). As a result, pain, inflammation, redness, swelling, and fever are reduced.

Dosage

600 mg twice daily

Pharmacokinetics

Amtolmetin readily absorbs after oral administration and Cmax (mean peak concentration) is 2 hours after administration. When this drug enters the system, it gets hydrolyzed into metabolites including tolmetin, MEDS and Guaciol. It mostly eliminates with urine as gluconides products (77%), and as fecal (7.5%).

Contraindications

  • Hypersensitivity to aspirin and NSAID
  • Treatment to peri-operative pain in coronary artery bypass  graft surgery
  • Patients with gastro-duodenal ulcer in active phase

Drug Interactions

  • Increased risk of abdominal pain and cramping  with mefipristone, a synthetic steroidal antiprogestogen
  • Increased risk of bleeding with anticoagulants, other NSAIDs, anti-platelets, low molecular weight heparin
  • Increased risk of convulsions with quinolones
  • Decreased antihypertensive response to loop diuretics and ACE inhibitors
  • Increased plasma concentrations on co administration with lithium, methotrexate and cardiac glycosides
  • Increased risk of nephrotoxicity with ACE inhibitors, penicillamine, cyclosporine, tacrolimus or diuretics

Side effects

Common (affecting between 1 in 10 to 1 in 100)

  • Nausea & Vomiting
  • Dyspepsia & Flatulence
  • Dizziness

Uncommon (affecting between 1 in 100 to 1 in 1000)

  • Gastrointestinal bleeding
  • Hypersensitivity reactions
  • Hypertension
  • Edema
  • Weight gain
  • Visual disturbances
  • Abnormal liver function
  • Erosive esophagitis
  • Tinnitus

Very rare (affecting less than 1 in 10,000)

  • Stevens- Johnson syndrome
  • Serious CV thrombotic events
  • Nephritic syndrome
  • Hepatitis

Precautions

Precaution is advised in following population:

  • Patients with impaired renal and hepatic function
  • Patients with a history of cardio vascular diseases, or heart failure
  • Patients with fluid retention, GI bleeding or gastric ulcers, dehydration or hypertension

Note: Renal function should be monitored regularly during administration of the drug

Clinic Evidence

  • A new non-steroidal anti-inflammatory drug (NSAID) amtolmetin guacyl (AMG) was significantly better than piroxicam in patients with osteoarthritis. Piroxicam shows serious side effects such as perforation, ulcer and bleeding but there were no serious side-effects observed with AMG. Piroxicam also shows epigastric and abdominal pain were more frequent and more intense than AMG. AMG was as effective as piroxicam in controlling the symptoms of osteoarthritis, but showed better gastrointestinal tolerability1.
  • Amtolmetin guacyl belongs to the NSAID class whose action is comparable to that of other drugs belonging to the same class, but with amtolmethin, a low incidence of collateral effects involving the gastric mucosa, equal to around 5%, has been reported in all clinical trials. It has been proven that amtolmetin guacyl provokes an increased production of nitric oxide (NO), an important mediator of the gastric mucosa defense system through the induction of the nitric oxide synthetase (NOS) enzyme ².

References

  1. Montrone F, Santandrea S, Caruso I, Gerli R, Cesarotti ME, Frediani P, et al. Int Med Res. 2000 Mar-Apr; 28(2):91-100.
  2. Biasi G, Marcolongo R. Minerva Med. 2001 Oct;92(5):315-24. ncbi.nlm.nih.gov/pubmed/11675575
  3. Bianchi Porro G, Montrone F, Lazzaroni M, Manzionna G, Caruso I. Ital J Gastroenterol Hepatol. 1999 Jun-Jul; 31(5):378-85.
  4. Hotha KK, Bharathi DV, Kumar SS, Reddy YN, Chatki P, et al. Biomed Chromatogr. 2010 Oct; 24(10):1100-7. ncbi.nlm.nih.gov/pubmed/20853464
  5. Tubaro E, Belogi L, Mezzadri CM. Eur J Pharmacol. 2000 Jan 10; 387(2):233-44. ncbi.nlm.nih.gov/pubmed/10650165
  6. Drugs.com:  drugs.com/international/amtolmetin-guacil.html
  7. MedCLICK: medclik.com/General/pages/Drugmanual/BrandSearch/ZEXTRA.asp

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