23 March 2020

Stop prescribing, dispensing hydroxychloroquine for COVID-19: PSA

Communicable Disease Drugs Rheumatology

The Pharmaceutical Society of Australia has asked prescribers, patients and pharmacists to step away from the hydroxychloroquine, after spruiking by US President Donald Trump last week left pharmacies short on supply.

Hydroxychloroquine, sold as Plaquenil, is a less-toxic derivative of the antimalarial chloroquine. Because of its anti-inflammatory effects it is used as a third-line treatment for rheumatoid arthritis, lupus, juvenile idiopathic arthritis and other autoimmune diseases.

Since President Trump touted the drug late last week in interviews and on Twitter, Australian pharmacies are already running dry, TMR has heard, with legitimate patients unable to get refills.

PSA president Associate Professor Chris Freeman wrote an open letter to prescribers on Saturday, saying pharmacists were reporting a surge in doctors prescribing for other doctors and their families, dentists doing the same and non-medical prescribers prescribing bulk amounts of the drug.

“If this medication does indeed have the efficacy that we would desire against COVID-19 then it needs to be prescribed and used judiciously,” Professor Freeman wrote.

“Our strong advice to pharmacists is to refuse the dispensing of hydroxychloroquine if there is not a genuine need, and that need is for those indications for what it is approved for – inflammatory conditions or the suppression and treatment of malaria.”

The evidence for the efficacy of hydroxychloroquine on COVID-19 comes chiefly from in-vitro research and one small, non-randomised French study by Gautret et al. published last week in the International Journal of Antimicrobial Agents.

In that study, “Twenty cases were treated … and showed a significant reduction of the viral carriage at D6-post inclusion compared to controls, and much lower average carrying duration than reported of untreated patients in the literature. Azithromycin added to hydroxychloroquine was significantly more efficient for virus elimination.”

Shane Jackson, PSA policy adviser and senior clinical lecturer at the University of Tasmania, said the French paper was best viewed as “a good hypothesis-generating study”.

“In this time of crisis, it doesn’t mean we throw evidence-based processes out the window,” he told TMR. “We have to follow evidence-based processes to understand whether these drugs will actually be effective or not.”

The PSA letter had three messages, he said: “Patients, don’t ask; prescribers, don’t prescribe; and pharmacists, do not dispense it off-label.”

He said the association had taken the “unprecedented step” of telling pharmacists to refuse to dispense for fear that users for approved indications would miss out because the drug was “sitting on someone’s shelf as a just-in-case measure”.

“I can tell you what I’ve done with my hydroxychloroquine: it’s in my safe with a note saying ‘not to be dispensed unless you call me’,” he said.

“We need to reserve that for the people who have already been on it for the legitimate TGA-approved indications of rheumatoid arthritis or lupus, for example. They potentially will be collateral damage when it comes to access to this medicine.”

According to the American College of Rheumatology, hydroxychloroquine is considered a disease-modifying anti-rheumatic drug that not only decreases pain and swelling of arthritis but also “may prevent joint damage and reduce the risk of long-term disability”.

“It is not clear why hydroxychloroquine is effective at treating autoimmune diseases,” the ACR says. “It is believed that hydroxychloroquine interferes with the communication of cells in the immune system.”

Side effects from hydroxychloroquine include retinal damage, allergic reaction, headache, dizziness, nausea, skin rashes and mood changes.

A commentary in The Lancet earlier this month by two French researchers noted the history of failed attempts to treat acute and chronic viral infections with chloroquine and hydroxychloroquine, and the lack of data available from a Chinese study reported to have positive results with COVID-19.

In Australia, clinical microbiologist and infectious disease physician Dr Bernard Hudson has expressed optimism about the ability of chloroquine and hydroxychloroquine to interfere with the acidification of the lysosomes and some of the membrane systems inside the cell.

“[I]n vitro it does actually inhibit replication of the SARS coronavirus. And the good thing is, is this is at clinically-achievable concentrations,” he said in a recent video lecture for Healthed.

“So it has been put forward that hydroxychloroquine or Plaquenil is a widely available drug that has both anti-inflammatory activities and antiviral activities and appears to be more potent than chloroquine at inhibiting the SARS coronavirus.

“In some of the places where they’ve had significant outbreaks, including both China and Italy, it has actually formed part of the treatment for people who need treatment.”

But he emphasised that most people with COVID-19 would not need treatment.

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