Many use malaria drug as coronavirus protection – but evidence lacking

Doug Hendrie

23/03/2020 4:16:21 PM

With the virus pushing health systems to the limit, many doctors are seeking out stocks of hydroxychloroquine and chloroquine.

Production of chloroquine
Australia’s peak pharmacy body has warned the rush for chloroquine could place patients using it for inflammatory conditions at risk. (Image: AAP)

After US President Donald Trump touted hydroxychloroquine and chloroquine as a possible ‘cure’ for coronavirus, there has been a rush for the drugs – even though the top US infectious diseases expert Dr Anthony Fauci has cautioned evidence is minimal.
The drugs are effective against coronaviruses in vitro, but a new French clinical trial has been widely criticised for a lack of rigour, rendering their favourable findings all but useless, according to a GP and evidence-based medicine expert.
Chinese researchers earlier claimed chloroquine was effective in trials with more than 100 patients, though the data from these trials have not been made public.
Despite the lack of evidence, the World Health Organization (WHO) has included them in its fast tracked global ‘megatrial’ of the four most promising treatments for the coronavirus.
In addition, new clinical trials are set to launch to test the effectiveness of the drugs against the coronavirus, with University of Oxford researchers planning to test chloroquine as a prophylactic for 10,000 healthcare workers in a trial starting in May. University of Queensland researchers are also planning a large clinical trial with 60 hospitals to test the drugs.
But the results from these clinical trials will not be known for many months, or even years.
The gap between the evidence base and the speed at which the new coronavirus is pushing health systems to the limits – and beyond – has led to many doctors seeking out stocks of the drug, just in case.
Australia’s peak pharmacy body has warned that the rush for the drug could place patients using it for inflammatory conditions at risk. It has called on pharmacists to refuse dispensing for purposes other than those clinically indicated.
‘The current stock of hydroxychloroquine [a newer, safer version of chloroquine] needs to be managed sensibly, it needs to be available for those who are currently being prescribed this medicine, and it may also be needed for treatment of COVID-19 [coronavirus] in the future,’ Pharmaceutical Society of Australia head Dr Chris Freeman wrote in an open letter.

In response, the Government has clamped down on prescribing of hydroxychloroquine to ensure sufficient supplies for existing patients.

In an amendment passed this week, the drug must now be first authorised by a dermatologist, intensivist, paediatrician, physician or emergency medicine specialist before GPs will be able to authorise an ongoing supply. 
Prominent Melbourne plastic and reconstructive surgeon Dr Allan Kalus told newsGP he is aware of many colleagues who are already using hydroxychloroquine as protection against the coronavirus, despite the current lack of strong clinical evidence .
‘Until new trials give us better evidence, doctors are left in the position of conducting their own risk–benefit analysis of whether it’s worth taking,’ he said.
‘People will say there’s no proof and I’d say you’re right, but this is a special situation where the disease is outrunning science. So we do need bold measures and interpretation of the science we do have.’
However, Dr Kalus said he does not want doctors – or the general public – to hoard the drug.
‘I’m not recommending anyone to take it. There is no absolute proof,’ he said. ‘But given the evidence in the lab, there’s no reason to think it wouldn’t help.
‘People at a high risk of contracting [COVID-19] could consider taking the drug as an added layer of protection in addition to social distancing and personal protective equipment.’
But evidence-based medicine expert Dr Daniel Aronov told newsGP the initial trial from France of hydroxychloroquine in combination with antibiotic azithromycin was too ‘poorly designed’ to allow any conclusions to be drawn from it.
Dr Aronov said the French trial was not randomised, did not report clinical outcomes and was biased in the way it selected controls for treatment.
‘I commend the authors for trying. The last thing you want to do when inundated with trauma, when no one [is] sleeping and everyone is scared, is to run a trial,’ he said.
‘Unfortunately, we don’t know what to do with the evidence. Plus, the community believes in this drug now so it’s very hard to design a trial with true randomisation.
‘The evidence for this is really poor at this stage. It’s not the golden ticket it’s made out to be in the media.
‘We just don’t know if it is effective or not. I very much hope it is, but I’m sceptical of our current evidence base.’
Dr Aronov said that it is common for a drug to be effective in vitro or even in animal trials, only to fail in human trials.
Despite the lack of evidence, Dr Aronov predicts most doctors will begin using it as a prophylactic.
‘On doctor [social media groups], most say they are now taking this drug,’ he said.
‘On the plus side, we have a lot of experience with this drug. We are familiar with its safety profile and its potential risks.’
The interest in hydroxychloroquine comes after a trial of anti-HIV drugs lopinavir and ritonavir published in the New England Journal of Medicine showed no benefit against coronavirus.
‘[Lopinavir and ritonavir] are first-line medications for HIV. They were looking promising against coronavirus after early research into SARS’ Dr Aronov said. ‘But now, when put to the rigour of a randomised clinical trial that’s been well conducted, they have been shown not to be effective.’
Australian National University (ANU) medical researcher and geneticist Dr Gaetan Burgio told newsGP he would counsel against using the drugs either as a prophylactic or treatment without results from a randomised clinical trial.
‘The recent clinical trial from France is inconclusive and flawed in my view,’ he said.
Dr Burgio said that to achieve the in vitro action against coronaviruses, much higher doses were required than for malaria, which could mean a higher risk of side effects.
GP Dr Evan Ackermann told newsGP that evidence for the drug is sparse, but given its low cost and relative safety, it could be worth using clinically in light of the lack of other options.
Pharmacologist Dr Phillip Reece told newsGP that after reviewing the published data, he has concerns about the potential efficacy of chloroquine as a treatment for coronavirus.
‘I would expect that, like influenza, the antiviral would need to be given early in the course of infection, that is, within two days of the first symptoms, to be effective,’ he said.
‘An oral regimen of chloroquine [at 300 mg a day] is unlikely to be effective based on pharmacokinetic grounds as concentrations attained within two days of starting the drug would be too low to be effective.’
Dr Reece said chloroquine could reach higher plasma concentrations if used prophylactically and hence be potentially effective in inhibiting the virus.
But Dr Reece stresses that reaching those concentrations ‘could well be toxic and not justified in otherwise healthy subjects’.
As the US Centers for Disease Control and Prevention points out in a review, both chloroquine and hydroxychloroquine have been linked to cardiotoxicity in the form of prolonged QT syndrome for long-term use.
The RACGP has more information on coronavirus, including self-isolation, available on its website.
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