Jacek Kaczmarczyk M.D.,Ph.D Ass.Prof.
Department of Orthopaedics and Traumatology, University of Medical Sciences in Poznan
28 Czerwca Street, no 135, 61-545 Poznan, POLAND
1) In your experience, is there any difference among the several products belonging to the pharmacological class of NSAIDs from a clinical point of view?
In my opinion, the choice of a given NSAID should be based on an accurate evaluation of the available evidence about the overall risk profile of the drug, and - more specifically - of the risk of possible side effects in a specific patient. The selectivity for the inhibition of a particular isoform of COX is very important from a pharmacological point of view. For example, drugs inhibiting preferentially COX-1 are aspirin, ketoprofen, indomethacin, and its precursor acemetacin, while those which present a similar affinity for COX-1 and COX-2 are lornoxicam, ibuprofen, naproxen, diclofenac, and nabumetone.
NSAIDs that inhibit preferentially COX-2 are nimesulide and meloxicam, while the only selective inhibitor of COX-2 currently registered in Poland is celecoxib.
The lower is the degree of COX-1 inhibition, the lower is the risk of damaging upper gastro-intestinal tract. Having that in mind, it seems that drugs (such as nimesulide) that preferentially or selectively inhibit COX-2 present an advantage in terms of tolerability. On the other hand, high selectivity towards COX-2 may be associated with an increased risk of cardiovascular side effects. Consequently, the optimal choice for minimizing side effects would be the use of preferential inhibitors of COX-2.
From a pharmacological point of view, there is an important parameter that should be taken into account: the plasma half-life of each drug. Drugs with a short half-life are safer because of a limited risk of accumulation in patients who have a reduced elimination. This is the reason why, among NSAIDs, we opt for those with a short half-life, especially in elderly patients.
I'd like to provide some recommendations for an appropriate choice of a NSAID in patients with acute osteo-articular pain:
- Only one NSAID should be used, at the smallest effective dose.
- Dosage should be adapted to the specific patient's pain rhythm/pattern.
- The possibility of interaction with other drugs should be taken into account.
- Prefer NSAIDs with short half-life, especially in case of elderly or of patients with other concomitant diseases.
- Evaluate carefully the risk of complications, especially with respect to gastro-intestinal system, kidney, and cardiovascular system. NSAIDs like indomethacin, naproxene , piroxicam, acethylsalicilic acid, ibuprofen, and diclofenac damage the mucosa of stomach and duodenum, by acting locally and systemically. Drugs administered as suppositories do not irritate the upper GI locally, but may do so systemically.
2) In your opinion, what are the most important features for an oral NSAID aimed at treating acute osteo-articular pain?
One of the most important features for an oral NSAID is the time to onset of the analgesic action. A fast onset of effect is the most desirable characteristics for most patients; this aspect needs to be taken into account in order to meet patients' expectations.
As I have already mentioned, the risk profile is very important, but we always have to keep in mind the therapeutic efficacy.
3) Which are the main reasons for choosing a specific NSAID for a specific patient?
In choosing a specific NSAID for a specific patient we shall take into account the pharmacokinetics of the drug, its pharmacological characteristics and the specific patients' needs. From the patient's point of view the most important factor is the drug effectiveness, in terms of fast onset and duration of the analgesic action. Fast and effective pain-killing is most appreciated by patients. From the physician's point of view, these features come together with an evaluation of the drug's risk profile.
Moreover, the choice of a NSAID should be based on the general rule of "primum non nocere"
4) What is your opinion about the benefit/risk profile of nimesulide?
The European Commission recently confirmed the opinion of the EMA CHMP about the positive benefit-risk profile of nimesulide. Large epidemiological studies have shown that the relative risk of liver damage associated with the use of nimesulide is very low. It is also worth mentioning that a few studies provide data on the hepatic effects of different NSAIDs. From the available scientific literature, we know that all NSAIDs share the same potential in terms of hepatotoxicity.
Anyway, it should be noted that the most common and alarming side effects of NSAIDs involve the gastrointestinal tract. As we know, the most remarkable risk of GI tract damage is associated with the use of NSAIDs that preferentially inhibit COX-1. Having that in mind, the opportunity of prescribing these NSAIDs shall be carefully evaluated, especially in patients with an elevated risk of GI complications. Many studies showed that nimesulide is characterized by a lower risk of GI side effects when compared with other NSAIDs such as ketoprofen, piroxicam, and diclofenac. We can therefore state that for Nimesulide, provided an appropriate use , at the lowest effective dose for no more than 15 days in line with its therapeutic indications, the benefits outweigh the risks.
Comment by Professor Leszek Romanowski, MD, PhD
Vice President of the Polish Orthopaedic and Trauma Society
Prof. Jacek Kaczmarczyk discussed drugs that are extremely important for the modern medicine. As inflammatory pain is present in a high number of diseases, NSAIDs are commonly used in all medical specialties. The main advantages of these drugs depend on the fact that they are effective, easily available, and generally inexpensive.
As outlined in this interview there are many NSAIDs, characterized by different pharmacokinetic and pharmacodynamics characteristics. Those with a shorter half-life should be used especially in elderly patients. NSAIDs which preferentially inhibit COX-2 can be used to reduce the risk of side-effects involving the upper gastro-intestinal tract. These aspects are very important for orthopedic patients, who suffer from both acute and chronic pain. NSAIDs with shorter half-life are also very important for the treatment of acute osteo-articular pain.
Thanks to their pain-killing effect, NSAIDs are also very useful for improving the outcome of rehabilitation in patients with several musculoskeletal disorders.
When choosing the most appropriate NSAID, we always have to take into account the benefit-risk profile of each molecule, as well as the characteristics of each single patient.
Experimental and clinical research in this field is very active, and therefore we expect that even more effective and safer anti-inflammatory drugs will be available in the near future.