Drugs

, Volume 34, Issue 3, pp 289–310

Tenoxicam

A Preliminary Review of its Pharmacodynamic and Pharmacokinetic Properties, and Therapeutic Efficacy
  • John P. Gonzalez
  • Peter A. Todd
Drug Evaluation

DOI: 10.2165/00003495-198734030-00001

Cite this article as:
Gonzalez, J.P. & Todd, P.A. Drugs (1987) 34: 289. doi:10.2165/00003495-198734030-00001

Summary

Synopsis

Tenoxicam1 is a new non-steroidal anti-inflammatory and analgesic agent of the oxicam class, and therefore closely related to piroxicam. It possesses a long half-life which enables it to be administered once daily. Clinical trials in patients with rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, gout and non-articular rheumatism suggest that tenoxicam 20mg daily is an equally effective anti-inflammatory and analgesic agent compared with piroxicam 20mg daily, and that it is at least as well tolerated. Additionally, a few small studies in rheumatoid arthritis and osteoarthritis suggest that tenoxicam 20mg daily is as effective and as well tolerated as usual therapeutic dosages of diclofenac, ibuprofen, indomethacin and naproxen. Transient mild or moderate gastrointestinal symptoms, in 8% of patients at a dosage of 20mg daily, are the most frequently reported side effects. If further studies confirm the initially favourable efficacy and tolerability findings, particularly the relatively low incidence of adverse effects, tenoxicam can be considered a useful new agent for the symptomatic treatment of rheumatic and inflammatory diseases, and a worthwhile alternative to other non-steroidal anti-inflammatory drugs.

Pharmacodynamic Studies

In standard animal models of inflammation tenoxicam was as potent as piroxicam, indomethacin and diclofenac, and was more potent than aspirin, mefenamic acid and naproxen. In kaolin-induced inflammation in rats, tenoxicam produced a 3-fold increase in pain threshold. Tenoxicam was at least as effective as piroxicam in standard animal models of analgesic activity. In animal tests of antipyretic activity tenoxicam was equivalent to indomethacin, weaker than piroxicam, diclofenac and naproxen, and more potent than aspirin. The therapeutic index of tenoxicam in rats, as determined from the ratio of the median ulcerogenic and anti-inflammatory doses, was superior to that of piroxicam, indomethacin, mefenamic acid, diclofenac, carprofen and aspirin.

In healthy subjects tenoxicam 20 or 40mg daily produced significantly less faecal blood loss than enteric-coated aspirin 3.6g daily, but there was no significant difference between tenoxicam and piroxicam at dosages of 20mg daily.

Tenoxicam, in common with other non-steroidal anti-inflammatory drugs, is an inhibitor of prostaglandin synthesis. It may also produce its anti-inflammatory effects by scavenging or inhibiting the production of active oxygen radicals, and by inhibiting leucocyte chemotaxis and phagocytosis.

Pharmacokinetic Properties

Following oral administration, mean peak plasma concentrations occur between 0.5 and 2 hours. The bioavailability of tenoxicam is about 100% after oral and 80% after rectal administration. Mean maximum plasma concentrations of about 2 and 4 mg/L, respectively, are attained after single oral doses of tenoxicam 20 and 40mg. Although food and antacids slow absorption and reduce peak plasma concentrations, they do not affect the overall extent of absorption. Steady-state plasma concentrations of about 11 mg/L are achieved 10 to 12 days after administration of tenoxicam 20mg once daily. The apparent volume of distribution is 0.15 L/kg in healthy subjects; mean elimination half-life is 60 to 75 hours and plasma clearance is 0.1 to 0.25 L/h. Over 99% of the drug is bound to human plasma protein in vitro. Tenoxicam readily penetrates the synovial fluid of patients with osteoarthritis or rheumatoid arthritis. About two-thirds of a dose of tenoxicam is recovered in the urine and one-third in faeces as inactive metabolites. No unchanged drug is excreted into bile. The major metabolite is 5′-hydroxytenoxicam in humans, and about one-third of a dose is recovered as this metabolite in urine. Data from small short-term studies suggest that the pharmacokinetics of tenoxicam are unaffected by age, sex, renal impairment, hepatic disease or rheumatic disorders, but these preliminary conclusions require confirmation in larger groups of patients treated for longer periods.

Therapeutic Trials

Tenoxicam has been studied in clinical trials involving patients with rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, gout and various non-articular inflammatory conditions. Many of these trials involved relatively small numbers of patients treated for short periods.

Tenoxicam has been most extensively studied in rheumatoid arthritis and osteoarthritis, and some of these studies included large numbers of patients treated for 6 months or longer. In these conditions tenoxicam 20mg daily was consistently shown to be at least as effective and well tolerated as piroxicam 20mg daily in a relatively large number of studies involving mostly small groups of patients. In a few additional small comparative studies tenoxicam was as effective as several other non-steroidal anti-inflammatory drugs. Increasing the dosage of tenoxicam to 40mg daily tended to improve efficacy, but increased the frequency of side effects.

Tenoxicam 20mg daily was equally as effective and well tolerated as piroxicam 20mg daily in the treatment of ankylosing spondylitis and non-articular rheumatism (e.g. tendinitis, bursitis, sciatica, back pain). Tenoxicam has not, however, been compared with other agents in these conditions. Limited data suggest that tenoxicam may be useful in the treatment of gout but no comparative studies have been reported.

Side Effects

At dosages routinely used in the treatment of rheumatic conditions, tenoxicam has been well tolerated. Gastrointestinal side effects have been the most frequent, occurring in 8% and 14% of patients treated with 20 and 40mg daily, respectively. Central nervous system complaints, such as headache and dizziness, have been reported occasionally, and there have been isolated reports of rash, urticaria and oedema. Withdrawal from therapy because of adverse reactions has been reported in 1.1% and 1.8% of patients with dosages of 20 and 40mg, respectively. A comparative analysis cumulating data from various sources suggests that the overall incidence of side effects with tenoxicam 20mg daily (10.6%) is about one-half that with piroxicam at the same dose (20.9%). However, the comparability of the treatment conditions in this analysis is unclear.

Dosage

The usual dosage of tenoxicam is 20mg once daily administered either orally or as suppositories. For acute attacks of gouty arthritis the recommended dosage is 40mg once daily for 2 days followed by 20mg once daily for a further 5 days.

Copyright information

© ADIS Press Limited 1987

Authors and Affiliations

  • John P. Gonzalez
    • 1
    • 2
  • Peter A. Todd
    • 1
    • 2
  1. 1.Suite 15C Manchester International Office CentreADIS Drug Information ServicesWythenshawe, Manchester, AucklandEngland
  2. 2.ADIS Drug Information ServicesAuckland

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