Tenoxicam

Absorption

Oral absorption of tenoxicam is rapid and complete (absolute bioavailability 100%).

Description

Tenoxicam is a non-steroidal antiinflammatory agent with a profile similar to related piroxicam and now withdrawn isoxicam (55). It is useful in the treatment of rheumatoid arthritis, osteoarthritis and related disorders.

Chemical properties

Yellow Crystalline Powder

Originator

Hoffmann-La Roche (Switzerland)

The Uses of Tenoxicam

Tenoxicam has been used:

• as a non-steroidal anti-inflammatory agent (NSAID) to study its effects on root gravitropism in Arabidopsis thaliana
• as a standard in microanalysis of NSAIDs by spectrophotometry
• to test its effect on surface potential andmembrane fluidity modification in phosphoglyceride monolayers

Background

Tenoxicam, an antiinflammatory agent with analgesic and antipyretic properties, is used to treat osteoarthritis and control acute pain.

What are the applications of Application

Tenoxicam is a nonsteroidal, anti-inflammatory, analgesic agent

Indications

For the treatment of rheumatoid arthritis, osteoarthritis, backache, and pain.

Definition

ChEBI: Tenoxicam is a thienothiazine-derived monocarboxylic acid amide obtained by formal condensation of the carboxy group of 4-hydroxy-2-methylthieno[2,3-e][1,2]thiazine-3-carboxylic acid 1,1-dioxide with the amino group of 2-aminopyridine. Used for the treatment of pain and inflammation in osteoarthritis and rheumatoid arthritis. It is also indicated for short term treatment of acute musculoskeletal disorders including strains, sprains and other soft-tissue injuries. It has a role as a non-steroidal anti-inflammatory drug, a non-narcotic analgesic, an antipyretic and an EC 1.14.99.1 (prostaglandin-endoperoxide synthase) inhibitor. It is a heteroaryl hydroxy compound, a monocarboxylic acid amide, a member of pyridines and a thienothiazine.

brand name

Tilcotil

Biochem/physiol Actions

Tenoxicam (TX) possesses antipyretic?and analgesic effects. It elicits radical scavenging activity and has the potential to treat enkylosing spondylitis, extra-articular diseases, acute gout, and rheumatic diseases. It is also effective in treating primary dysmenorrhea, postpartum uterine contraction pain, and post-operation backaches. TX is capable of inhibiting prostaglandin synthesis.

Pharmacokinetics

Tenoxicam, an antiinflammatory agent with analgesic and antipyretic properties, is used to treat osteoarthritis and control acute pain.

Clinical Use

NSAID and analgesic

Synthesis

The reaction of methyl 3-hydroxythiophene- 2-carboxylate with PCl5 in refluxing CCl4 gives 3-chlorothiophene-2-carboxylic acid, which by treatment with NaHSO3 and Cu in aqueous alkaline solution at 143 ?C in a pressure vessel is converted into 3- sulfothiophene-2-carboxylic acid. Its esterification with refluxing methanol affords methyl- 3-sulfothiophene-2-carboxylate, which by reaction with refluxing SOCl2 yields methyl- 3-chlorosulfonylthiophene-2-carboxylate. The following condensation with sarcosine ethyl ester in hot CHCl3 gives 3-(N-ethoxycarbonylmethyl- N-methylsulfamoyl)thiophene-2-carboxylate, which is cyclized by treatment with sodium methoxide in refluxing methanol affording 3-ethoxycarbonyl-4-hydroxy-2-methyl-2Hthieno--1,2-thiazine 1,1-dioxide. Finally this compound is condensed with 2-aminopyridine in refluxing toluene

Drug interactions

Potentially hazardous interactions with other drugs
ACE inhibitors and angiotensin-II antagonists: antagonism of hypotensive effect; increased risk of nephrotoxicity and hyperkalaemia.
Analgesics: avoid concomitant use of 2 or more NSAIDs, including aspirin (increased side effects); avoid with ketorolac (increased risk of side effects and haemorrhage).
Antibacterials: possibly increased risk of convulsions with quinolones.
Anticoagulants: effects of coumarins and phenindione enhanced; possibly increased risk of bleeding with heparins, dabigatran and edoxaban - avoid long term use with edoxaban.
Antidepressants: increased risk of bleeding with SSRIs and venlaflaxine.
Antidiabetic agents: effects of sulphonylureas enhanced.
Antiepileptics: possibly increased phenytoin concentration.
Antivirals: increased risk of haematological toxicity with zidovudine; concentration possibly increased by ritonavir.
Ciclosporin: may potentiate nephrotoxicity.
Cytotoxics: reduced excretion of methotrexate; increased risk of bleeding with erlotinib.
Diuretics: increased risk of nephrotoxicity; antagonism of diuretic effect; hyperkalaemia with potassium-sparing diuretics.
Lithium: excretion decreased.
Pentoxifylline: increased risk of bleeding.
Tacrolimus: increased risk of nephrotoxicity.

Metabolism

Tenoxicam is metabolized in the liver to several pharmacologically inactive metabolites (mainly 5'-hydroxy-tenoxicam).

Metabolism

Metabolised in the liver via cytochrome P450 2C9 to several pharmacologically inactive metabolites (mainly 5'-hydroxy-tenoxicam).
Metabolites are excreted mainly in the urine; there is some biliary excretion of glucuronide conjugates of the metabolites.