Analgesic Efficacy and Safety of Lornoxicam Quick-Release Formulation Compared With Diclofenac Potassium

N. Yakhno; A. Guekht; A. Skoromets; N. Spirin; E. Strachunskaya; A. Ternavsky; K.J. Olsen; P.L. Moller


Clin Drug Invest. 2006;26(5):267-277. 

In This Article


This study demonstrated that lornoxicam administered as a quick-release formulation is not inferior to the equivalent formulation of diclofenac potassium in terms of onset of PAR in patients presenting with acute low back pain. Although the difference observed between both drugs for time to onset of PAR (lornoxicam: 30 minutes vs diclofenac potassium: 36 minutes; ITT analysis) was not statistically significant, it should be noted that the 6-minute difference was very close to the difference that was defined as clinically relevant between both drugs (20% of the diclofenac potassium time to onset, i.e. 7 minutes). Time to onset of PAR with lornoxicam in this study was similar to that observed in a previous study that compared the quick-release formulation of lornoxicam with the standard tablet formulation in dental surgery (32 minutes vs 45 minutes).[16] This formulation also proved to be significantly better than the quick-release formulation of diclofenac potassium in terms of magnitude of effect, as demonstrated by higher PIDs, SPID, peak effects and on the patients' global evaluation of treatment.

Lornoxicam is a highly potent NSAID belonging to the chemical class of oxicams. The drug exhibits anti-inflammatory and analgesic activity in various experimental models for acute and chronic painful inflammatory processes and is approximately ten times more potent than the other oxicams, piroxicam and tenoxicam. It has also been shown to be at least as effective as naproxen, ibuprofen, ketorolac and diclofenac.[14]

Available formulations of lornoxicam include standard film-coated tablets, quick-release film-coated tablets, powder for injection and suppositories. Lornoxicam (4mg twice daily) administered as a standard tablet demonstrated similar efficacy to diclofenac (50mg twice daily) in patients with moderate to severe chronic low back pain.[6] In an open clinical study, 16mg of intramuscular lornoxicam followed by 8mg administered intramuscularly up to twice daily proved to be well tolerated and effective for the treatment of acute low back pain.[19]

The quick-release formulation, designed to obtain a high peak plasma concentration, was developed to achieve early pain relief following oral administration. Bioequivalence between this formulation and the intramuscular formulation of lornoxicam has been demonstrated (manuscript in preparation). Based on the plasma concentration profile of lornoxicam obtained with the quick-release tablet, which is similar to the profile of the intramuscular injection, an initial dose of 16mg (twice the usually recommended dose of 8mg) was selected in order to mimic the intramuscular injection in terms of plasma concentration. The initial dose of the comparator, diclofenac potassium, was determined accordingly and identified as twice the recommended dose of 50mg. Use of a higher first dose of analgesics such as NSAIDs is now common practice with some conditions, for example in the postoperative setting. This practice allows for appropriate management of acute pain at the time when the pain is severe and when the patient needs rapid relief from pain. In our study, administration of a high initial dose was effective, as illustrated by clinically significant pain relief scores, limited use of rescue medication and satisfactory global evaluation by the patient following the first drug administration. Furthermore, based on the positive findings for pain relief scores, use of rescue medication, ability to perform daily activities and global evaluation by the patient, the dose regimen for the entire study period seems to have been appropriately selected. Although lornoxicam was administered in a quick-release formulation, the time to intake of rescue medication did not indicate a shorter duration of analgesic effect for lornoxicam than for diclofenac potassium.

Low back pain was selected as a pain model to characterise the analgesic effect of lornoxicam in terms of onset of PAR (primary criterion), magnitude of effect and peak effect. This model is a recognised pain model for evaluation of analgesics in acute pain.[20] Guidelines for analgesic trials recommend avoiding any other treatments that can modulate perception of pain (i.e. physical therapy, psychological support). Therefore, therapies commonly advocated for the treatment of low back pain such as muscle relaxants, exercise or lumbar support were not allowed during the trial.

Although placebo-controlled designs are recommended in analgesic trials in order to assess the downside sensitivity of the study methods and therefore to validate the study,[21] no placebo group was included in the study as both drugs have already demonstrated their analgesic efficacy in comparison with placebo.

The pain scales used in the study (11-point numerical rating scale for pain intensity and 5-point verbal rating scale for pain relief) are classic scales that are recommended in analgesic guidelines.[2,9] The 11-point numerical rating scale showed a more consistent statistically significant difference between lornoxicam and diclofenac potassium than did the 5-point verbal scale. The reason may be that smaller differences may be detected with the more detailed numerical rating scale.

Safety studies in humans have evaluated single doses of lornoxicam up to 160mg without evidence of serious toxicity. Data from numerous clinical studies conducted in postoperative pain, lumbar conditions, osteoarthritis and rheumatoid arthritis with doses ranging from 2 to 32 mg/day suggest that lornoxicam has an extremely favourable adverse effect profile with no apparent differences in the overall incidence of adverse events between lornoxicam and placebo.[14] In this study, both formulations were equally well tolerated. The most frequently reported adverse events were gastrointestinal disorders, dizziness and headache, which are well known with treatment with NSAIDs.


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