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Gatifloxacin and side effects

Posted by draniltuladhar on 20 Jul 2007 at 20:10 GMT

I read with interest an article published on PloS online journal on 27th June 2007. It is a very interesting article and if proven without a side-effect Gatifloxacin could be a wonder drug for a developing country like Nepal.

However, more I read about Gatifloxacin, more worried I became. This is a drug which has been on “Black Box” warning in USA, not licensed in the UK and withdrawn from European Market for at least few years for its life-threatening side effects like dysglycaemia and 10% mortality in one of the Canadian study in elderly group and there is no concrete evidence to suggest that it is neither safe nor harmful in younger adults including children. I was amazed to see that the investigators didn’t even look into the blood sugar on this trial, the very reason why Gatifloxacin came to disrepute. I would have thought the result then would have either been more robust or otherwise in support of Gatifloxacin. The authors tried in their defence of omitting blood sugar level by quoting another study involving children.(Pichichero ME, Arguedas A, Dagan R, Sher L, Saez-Lorens X, et al. (2005) Safety and efficacy of gatifloxacin therapy for children with recurrent acute otitis media (AOM) and/or AOM treatment failure. Clin Infect Dis 41: 470–478.) The safety data in this study is hardly enough to conclude that Gatifloxacin is safe.

RE: Gatifloxacin and side effects

NJWhite replied to draniltuladhar on 23 Jul 2007 at 10:38 GMT

I was a member of the data and safety monitoring committee for this trial. It is important to know that this trial was started well before any information on gatifloxacin and blood glucose control was in the public domain. As soon as the Canadian study was published we reconsidered the risks and benefits of gatifloxacin in this trial (even though it had nearly finished). We concluded that we could not extrapolate the findings from an elderly Canadian population in whom dysglycaemia would be frequent, to a largely young and previously fit Nepali population. Obviously future studies should include increased vigilance for hypoglycaemia or hyperglycaemia to assess the risk if any. Meanwhile the investigators have shown that gatifloxacin is remarkably effective, and is well tolerated, and is thus an important advance in the treatment of quinolone resistant typhoid fever -a potentially life threatening disease. The benfits are thus established, and any potential risks must be balanced against these.

RE: RE: Gatifloxacin and side effects

draniltuladhar replied to NJWhite on 24 Jul 2007 at 17:54 GMT

Thanks for Prof. White’s reply. There is no doubt that this study has proven that Gatifloxacin is efficacious in decreasing the days of defervescence with decreased relapsed rate.

However, I believe it is premature to conclude its efficacy without giving attention to its potentially fatal dysglycaemic side effects. I completely agree that the Canadian study was published only after the termination of this study in question. But there have been number of other studies highlighting this particular side effect of Gatifloxacin irrespective of blood glucose status of the patients. Hence, authors should have at least mentioned about this potential side effect in their abstract (since the article was submitted for publication almost a year after the Canadian study was published).

I am bringing this to everyone’s attention repeatedly because once the drug is approved, they are unscrupulously available over the counter in Nepal and one doesn’t need prescription to buy these drugs. Most of the local pharmacists themselves prescribe these drugs to the patients without any sort of monitoring system in place. In short, I don’t know about Vietnam and Thailand, once approved there are no stringent measures in place to monitor the drug usage and its side effects in Nepal.

Your study population was very well followed and the complications were picked up and dealt with early by the health workers. But this is not the true reflection of what happens with the patients on day to day basis. In developing country like Nepal, as it is, enteric fever is potentially fatal disease, if there is not going to be any robust stringent measures to monitor these patients of this potentially fatal side effect, it will be impossible to ascertain the cause of death in these patients.

Hence, we need to have robust trial confirming that dysglycaemic side effects of Gatifloxacin are common only in elderly patients and not in younger population before showing a green light to Gatifloxacin. It is premature to conclude that we should prefer Gatifloxacin with unproven potentially fatal side effects, to other drugs which have known minor side effects.

For every approved indication for Gatifloxacin, there are safer, equally effective, and less costly alternatives. In comparison with other recent experiences regarding adverse drug effects, this choice should not be a difficult one for physicians, patients, regulators, and manufacturers.

Lastly, I would like to hear from either authors or readers, whether there are any trials looking into this particular side effect of Gatifloxacin for its other indications in the developed world (I stress here not developing countries) following the Canadian study. That will be very interesting to see.