Drugs

, Volume 51, Issue 4, pp 639–657

Lornoxicam

A Review of its Pharmacology and Therapeutic Potential in the Management of Painful and Inflammatory Conditions
  • Julia A. Balfour
  • Andrew Fitton
  • Lee B. Barradell
Drug Evaluation

Abstract

Synopsis

Lornoxicam (chlortenoxicam), a new nonsteroidal anti-inflammatory drug (NSAID) of the oxicam class with analgesic, anti-inflammatory and antipyretic properties, is available in oral and parenteral formulations. It is distinguished from established oxicams by a relatively short elimination half-life (3 to 5 hours), which may be advantageous from a tolerability standpoint.

Data from preliminary clinical trials suggest that lornoxicam is as effective as the opioid analgesics morphine, pethidine (meperidine) and tramadol in relieving postoperative pain following gynaecological or orthopaedic surgery, and as effective as other NSAIDs after oral surgery. Lornoxicam was also as effective as other NSAIDs in relieving symptoms of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, acute sciatica and low back pain. Lornoxicam has a tolerability profile characteristic of an NSAID, with gastrointestinal disturbances being the most common adverse events.

Limited clinical experience to date suggests that, as with a number of other NSAIDs, lornoxicam may provide a better-tolerated alternative or adjuvant to opioid analgesics for the management of moderate to severe pain. It has also demonstrated potential as an alternative to other NSAIDs for the management of arthritis and other painful and inflammatory conditions. These preliminary findings require confirmation in further comparative and long term studies.

Pharmacodynamic Properties

As with other nonsteroidal anti-inflammatory agents (NSAIDs), lornoxicam (chlortenoxicam) inhibits prostaglandin (PG) synthesis via inhibition of cyclo-oxygenase, but it does not inhibit 5-lipoxygenase. Lornoxicam was reported to be 100-fold more potent (on a molar basis) than tenoxicam in inhibiting PGD2formation in rat polymorphonuclear leucocytes in vitro and more active than indomethacin or piroxicam in preventing arachidonic acid-induced lethality in mice in vivo.

Lornoxicam has demonstrated analgesic and anti-inflammatory activity in both animal and human models. It produced dose-related analgesia in the human dental extraction model and showed approximately 10-fold greater analgesic activity than tenoxicam in the acetylcholine-induced writhing test in mice. It was also 10-fold more active than tenoxicam in inhibiting carrageenin-induced oedema in the rat and paw swelling in the adjuvant-induced polyarthritic rat.

In comparative studies in healthy volunteers, lornoxicam 16 mg/day induced significantly less endoscopically verified gastroduodenal injury than naproxen 1000 mg/day, and lornoxicam 8 mg/day tended to cause less faecal blood loss than indomethacin 100 mg/day. Moreover, lornoxicam did not increase serum pepsinogen I levels (an index of gastric mucosal status), when given at a dosage of 4mg twice daily for 2 weeks.

Studies in healthy volunteers and patients with renal impairment did not reveal any evidence of nephrotoxicity following administration of lornoxicam (≤16 mg/day for ≤3 weeks).

Pharmacokinetic Properties

Lornoxicam is completely absorbed after oral administration, reaching peak plasma concentrations of 270 μg/L within 2.5 hours after a 4mg dose. It exhibits dose-related kinetics over a dosage range of 2 to 6mg twice daily. The absorption of lornoxicam is delayed and marginally reduced (≈20%) in the presence of food. Instances of excessively high plasma concentrations associated with delayed drug elimination in healthy volunteers suggest that lornoxicam metabolism may be impaired in certain individuals.

As with other oxicam NSAIDs, lornoxicam is highly bound (99%) to plasma proteins with a low apparent volume of distribution (0.2 L/kg). However, it readily penetrates into perivascular interstitial spaces, including synovial fluid.

Lornoxicam is extensively metabolised in the liver, to the inactive metabolite 5′-hydroxy-lornoxicam. Excretion is shared between the renal (42%) and faecal (51%) routes. Lornoxicam has a relatively short terminal plasma elimination half-life (mean 3 to 5 hours in healthy young volunteers), with considerable interindividual variability.

The pharmacokinetics of lornoxicam do not appear to be appreciably modified by advanced age or renal impairment, but accumulation of the inactive major metabolite occurred in patients with impaired hepatic function. Enhanced enterohepatic elimination of the drug may compensate for reduced renal elimination in those with severe renal dysfunction.

Therapeutic Potential

Acute Pain. A small number of preliminary placebo-controlled and other comparative clinical studies have shown that lornoxicam provides effective analgesia following oral or other surgery. Intravenous lornoxicam 8mg was reported to be as effective as pethidine (meperidine) 50mg and at least as effective as tramadol 50mg in providing intravenous analgesia following gynaecological or orthopaedic surgery. Lornoxicam was also comparable to morphine for patient-controlled analgesia in an orthopaedic setting. When used after oral surgery, oral lornoxicam 8mg was as effective as oral ketorolac 10mg, ibuprofen 400mg and aspirin (acetylsalicylic acid) 650mg.

In patients with acute sciatic or lumbosciatic pain, lornoxicam 8mg twice daily was superior to placebo and comparable to oral diclofenac 50mg 3 times daily.

Chronic Pain. In short term (up to 3 months) randomised, double-blind studies, lornoxicam (orally administered in dosages ranging from 4mg twice daily to 8mg twice daily) exhibited efficacy similar to diclofenac in osteoarthritis; diclofenac, naproxen or piroxicam in rheumatoid arthritis; indomethacin in ankylosing spondylitis, and diclofenac or naproxen in low back pain. Although some slight differences in efficacy parameters were noted, none of these were statistically significant. The efficacy of lornoxicam was maintained during long term studies of up to 1 year’s duration in patients with osteoarthritis or rheumatoid arthritis. Lornoxicam 4mg 3 times daily was also reported to be superior to placebo for prophylaxis against migraine.

Tolerability and Drug Interactions

Lornoxicam has a tolerability profile characteristic of NSAIDs, with gastrointestinal disturbances (pain, dyspepsia, nausea, vomiting) being the most prominent events. In comparative clinical trials, the tolerability of oral lornoxicam appeared to be similar to that of diclofenac and better than that of indomethacin in patients with arthritic conditions or chronic low back pain. As would be expected, parenterally administered lornoxicam tended to be better tolerated than parenteral opioid analgesics in patients with postoperative pain.

The pharmacokinetics of lornoxicam are not significantly modified by coadministered antacids or ranitidine. Lornoxicam appears to share with other NSAIDs pharmacokinetic and/or pharmacodynamic interactions with Cimetidine, warfarin, sulphonylureas, lithium, furosemide (frusemide) and methotrexate. Lornoxicam did not alter phenazone (antipyrine) clearance in healthy volunteers, indicating a lack of effect on hepatic drug metabolising enzymes.

Dosage and Administration

The most common dosages of lornoxicam used in clinical trials were 4mg twice or 3 times daily or 8mg twice daily (orally) for management of arthritic conditions, low back pain and ankylosing spondylitis, and single or repeated doses of 4 or 8mg (orally or intravenously) for management of postoperative pain.

Caution is recommended when using lornoxicam in patients with impaired renal function (although dosage adjustment does not appear to be necessary) and in those receiving warfarin, oral sulphonylureas, loop or thiazide diuretics, or digoxin.

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Copyright information

© Adis International Limited 1996

Authors and Affiliations

  • Julia A. Balfour
    • 1
  • Andrew Fitton
    • 1
  • Lee B. Barradell
    • 1
  1. 1.Adis International LimitedMairangi Bay, Auckland 10New Zealand

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