It’s available and it’s affordable. But science still doesn’t know enough to back the antimalarial drug chloroquine for widespread use against the new coronavirus. A new trial in South Africa may change that at home — and abroad.
Some South African doctors are prescribing unproven treatments for the new coronavirus, warns the national drug regulator. The caution comes as the country prepares to join a global trial to discover possible treatments for the virus.
The South African Health Products Regulatory Authority (SAHPRA) has called on doctors to stop prescribing the medication chloroquine to prevent infection with the new coronavirus or to treat the disease it causes, COVID-19, outside of hospitals.
The warning comes after some pharmacies have run out of the drug.
In a 23 March statement, SAHPRA CEO Boitumelo Semete-Makokotlela said pre-emptive prescribing of chloroquine was leading to “fear-based stockpiling of potentially life-saving medicines” and was a serious misuse of the drug.
Although chloroquine was traditionally used to prevent and treat malaria, rising rates of drug-resistant malaria has led to it being replaced by other treatments, explains University of Cape Town professor of clinical pharmacology Karen Barnes. Chloroquine is, however, still used to treat other diseases like rheumatoid arthritis or the autoimmune disease lupus erythematosus.
There is not enough evidence to know whether the drug protects against infection from the new coronavirus, known as SARS-CoV-2. Scientists are still trying to determine if it can be used to treat COVID-19. South Africa will join a global trial, spearheaded by the World Health Organisation, in the coming months to help answer this question. Meanwhile, chloroquine has been slated for limited use in South Africa’s COVID-19 response.
On Friday, the national health department released new guidelines on the testing and treatment of the new coronavirus. The document allows for chloroquine use only in hospitalised patients with severe COVID-19 and who are part of a clinical trial or have consented to use the experimental treatment.
Doctors prescribing the drug to patients like these who are not in a trial will be required to fill out forms to allow SAHPRA to monitor the use of the drug and possible side effects. This is part of what the drug regulator calls its Monitored Emergency Use of Unregistered Interventions (MEURI) framework.
South Africa to participate in global COVID-19 trial
Monitoring patients will be especially important because doctors still aren’t sure how much chloroquine might be needed to treat COVID-19 — if it actually works, Barnes explains.
When the medication was used to prevent malaria, patients would only take it once a week. But the dosages that may be needed for COVID-19 are likely to be significantly higher and this may increase the risk of some side effects, such as diarrhoea, itchy skin or vomiting, she says.
The World Health Organisation is currently running an international clinical trial to evaluate whether four drugs or combinations of drugs — including possibly chloroquine — could treat COVID-19.
The study, which will also take place in South Africa, will randomly assign volunteers to one of five treatment options.
Some will receive a duo of antiretroviral drugs with or without a multiple sclerosis drug called Interferon beta-1a. Another group will be given a medicine once tested as an Ebola treatment. And a fourth cluster of participants will take either chloroquine or a closely related drug called hydroxychloroquine, according to a health department press release.
And finally, these groups will be compared to patients receiving standard care for COVID-19. Because the disease affects the lungs, standard care for COVID-19 patients focuses mostly on helping patients breathe and giving them oxygen.
South Africa’s new COVID-19 guidelines note that chloroquine’s affordable price — it can cost between R2 to R5 per pill — may tempt doctors to prescribe. But the document also cautions that while chloroquine has shown some promise treating infected cells in labs, there is no evidence from large trials in humans to show that it works to prevent or treat COVID-19.
Earlier this month, a paper published in Clinical Infectious Diseases assessed the use of both chloroquine and hydroxychloroquine in cells infected with the SARS-CoV-2 virus. The research found that while both drugs worked to help stop the virus from replicating — hydroxychloroquine was somewhat better than chloroquine at this — there was no evidence to support its use in treating COVID-19.
And what happens to cells in the lab can be a far cry from what happens in humans in the real world, University of KwaZulu-Natal senior pharmacy lecturer Andy Gray told Bhekisisa earlier this month.
“Even if there are medications that work in cells, that doesn’t necessarily mean that they will work if you try and give them to patients. There are a lot of differences between how something interacts in a cell in a petri dish versus how it interacts with someone’s body,” Gray says.
“When it comes to testing drugs in human trials, the failure rate is high.”
Abuse the drugs we have now and we may pay later
New guidelines follow a previous 19 March draft document that recommended the use of chloroquine for not only hospitalised patients, but also mild cases who were at risk of developing severe symptoms. Although these guidelines were circulated among healthcare workers, the health department never approved the document.
SAHPRA has granted the firm Austell Pharmaceuticals special permission to import 500 000 chloroquine tablets. In a 26 March press release, the company confirmed it would be donating the medication to the national health department. Austell Pharmaceuticals’ statement incorrectly cites the unapproved 19 March guidelines as the government’s official recommendation that the drug be used in mild cases of COVID-19.
Hydroxychloroquine is not currently registered for use in South Africa. Meanwhile, chloroquine, which is registered, remains open to overuse and misuse, Barnes warns.
Unregulated and arbitrary prescription of the medication is not only not backed by science yet, it’s also a missed opportunity to gain information on possible coronavirus treatments in a way that could be useful for future outbreaks.
She concludes: “This was a problem with the Ebola outbreak. People were so desperate to help patients that they often treated them with whatever they could, however they could. We got to the end of that awful epidemic without really knowing enough should an infection like that come our way again.
“It’s lost knowledge and we are very wary of that happening with the COVID-19 pandemic.”
[11:47am 1 April 2020: This story was updated to provide more details regarding the evidence for hydroxychloroquine use from human trials.]