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Know
nimesulide better, then prescribe: Warn experts
A
Special Correspondent - Mumbai
At
a time when nimesulide market is growing fast and is displacing
paracetamol faster, experts warn that in view of the global cautionary
approach to this NSAID, clinicians and pharma companies may need
to look deeper into the safety profile of the drug.
The
DCGI and the DTAB could possibly undertake an exercise to rule out
the possibility of nimesulide-induced arrhythmias considering its
structural type to drugs like dofetilide and sotalol which are implicated.
‘Torsade
de Pointes’ is a life threatening left ventricular arrhythmia
that is triggered by an imbalance caused in the ion channels in
our bodies at the cellular level. This could be drug-induced and
the problem is known to be associated with antihistamines like terfenadine
and astemizole, particularly in association with increased blood
concentrations.
A
specific type of K+ channel known as HERG regulating potassium current
in the cardiac potential gets disturbed leading to long QT syndrome
detectable on the ECG. A large number of drugs interact with HERG
leading to cardiotoxicity.
Drugs
like cisapride, ondansetron, haloperiodol, erythromycin are known
to cause this syndrome particularly when co-administered with drugs
suppressing hepatic metabolism. There are some methanesulphonanilide
compounds like dofetilide & sotalol that interact with HERG.
Nimesulide, a widely used NSAID in India is another drug having
the methanesulphonanilide pharmacophore (CH3.SO2.NH-) The question
is, do all methanesulphonanilide compounds cause QT prolongation?
Is nimesulide under a cloud internationally due to this reason in
addition to its known liver toxicity & GI associated problems?
Answers that clinicians, medical advisors and marketing gurus of
pharma companies need to know. Dofetilide is a drug having two methanesulphonanilide
structures and sotalol and nimesulide have one each. If a wide range
of drugs interact with HERG, structural types can be problematic
and are a matter of concern. There are problems with drug metabolites
too. Terfenadine, having serious interaction with HERG, gets metabolised
to fexafenadine which does not interact with HERG. However, if hepatic
metabolism is impaired or suppressed, then fexafenadine is not formed
& cardiotoxicity of terfenadine is assured. In the case of astemizole,
its desmethyl metabolite is more potent when it comes to interaction
with HERG. The chances of surviving a Torsade de Pointes episode
is 50:50. It would be worthwhile to know about the metabolites of
nimesulide and how they react with HERG. Nimesulide may be a good
selective COX-2 inhibitor, but experts believe that it has just
marginal advantages and doubt any breakthrough benefits. They say
that marketing departments gloss over the advantages and do not
bother about cautioning on the safety issues. “The clinicians
do not have much idea about chemistry and those with chemistry background
unfortunately are not good at medicine,” say researchers. However,
experts in India are unsure if even simple in-vitro testing are
done on drugs to know if they inhibit HERG channel activity before
they are introduced in the market. When death due to cardiac reasons
is the number one killer, someone has to ensure that drug-induced
problems do not add to such fatalities.
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