The Indian Council for Medical Research released a statement on Monday recommending the use of the anti-malarial drug hydroxychloroquine as a preventive medicine for those who face a high risk of coronavirus infection, provided they do not have any symptoms of the disease.

High-risk individuals include healthcare workers involved in the care of suspected or confirmed cases of Covid-19 and household contacts of laboratory confirmed cases. The ICMR director Balram Bhargava emphasised that the recommendation applies only to these two categories of people and only for pre-exposure prophylaxis – or prevention before exposure.

But this advice is likely to be ignored. The drug is already out of stock in many online pharmacies as panicked Indians have started hoarding hydroxychloroquine and another anti-malarial medicine chloroquine in the hope that the drugs are effective against Covid-19. At the moment, the hope is not based on facts. In fact, those who self-medicate face the risk of serious side-effects.

The buying spree began even before the ICMR announcement – United States President Donald Trump set it off actually, as this piece explains, before taking a closer look at the concerns around the use of the drugs to fight Covid-19.

What are chloroquine and hydroxychloroquine?

Chloroquine is primarily an anti-malarial drug discovered in 1934. It is part of the World Health Organisation’s list of essential medicines. It is also used in the treatment of lupus and rheumatoid arthritis – patients need to take the drug for years. Hydroxychloroquine is also from the same family with similar indications and usually preferred over chloroquine for long term use because of lesser toxicity.

Why was chloroquine tried for Covid-19?

The antiviral effects of chloroquine was described in a research paper published in the Lancet in 2003. Chloroquine was reported to be effective in preventing the spread of SARS CoV – severe acute respiratory syndrome-related coronavirus – in lab settings in 2005.

Researchers have tried this drug in HIV and several ongoing clinical trials have attempted to establish the use chloroquine analogs in the prevention or treatment of several viral infections, including hepatitis, rabies, chikungunya, Ebola virus disease, influenza A and B, and dengue viral infections. A limiting factor in most of these studies were the high levels of chloroquine required inside the cells for meaningful action against virus entry. This meant overall increase in drug toxicity.

How toxic is chloroquine and HCQ?

The exact frequency of side effects, called adverse reactions in medical parlance, is not reported. The life-threatening toxicities are mainly heart related in the form of disturbed heart rhythm and heart failure. Patients are usually advised ECGs before and during treatment.

The other much talked about toxicity is irreversible blindness from retinal toxicity, though it is usually not seen in short duration treatment. Patients undergo retinal examination before treatment and yearly. It is not given to patients who already have some retinal diseases.

It is also reported to cause fatal lowering of blood glucose, decrease in blood counts and loss of muscle strength. Increased suicidal tendencies and depression are other serious toxicities.

Needless to say, self medication without a proper indication is dangerous.

Are chloroquine and HCQ effective for Covid-19 treatment?

The data for effectiveness of chloroquine comes from two small studies from China and France and some anecdotal reports of successful treatments in the social media including the case treated in Jaipur in Rajasthan.

The combination of HCQ and azithromycin, an antibiotic drug, was found to be better than HCQ alone in a non-randomised trial. An infection disease expert pointed out the weaknesses of the trial – six out of 26 cases involved in the trial were ineligible, it had a lower threshold for negative, which were described an Infectious disease expert.

The overall evidence so far for chloroquine and HCQ and its combination with azithromycin is very thin.

What did Elon Musk and Donald Trump do?

On March 17, Elon Musk tweeted that chloroquine may be considered for Covid-19 and HCQ may be probably better.

This was followed by statements by Donald Trump hyping up the combination of HCQ and azithromycin as a possible cure for Covid-19. He also made controversial remarks on the need for testing these drugs before using.

What is the position of the WHO and the United States FDA?

The World Health Organisation has not approved the use of chloroquine for Covid-19 yet.

On March 19, the commissioner of the US Food and Drug Administration announced:

“We also must ensure these products are effective; otherwise we risk treating patients with a product that might not work when they could have pursued other, more appropriate, treatments. At the same time, we will engage with domestic manufacturers to ramp up production of this product to mitigate any potential supply chain pressures... We will take all steps to ensure chloroquine remains available for patients who take it to treat severe and life-threatening illnesses such as lupus.”

The FDA also said: “While there are no FDA-approved therapeutics or drugs to treat, cure or prevent COVID-19, there are several FDA-approved treatments that may help ease the symptoms from a supportive care perspective.”

What were the consequences of the hype?

Indian pharmaceutical companies got large US orders and their stocks went up. Trump’s endorsement had a worldwide effect and multiple reports of drugs going out of stock and price hikes surfaced. The United Kingdom banned the export and hoarding of HCQ. Three people were hospitalised in Nigeria from chloroquine poisoning after Trump’s announcement.

What are the potential consequences of India’s announcement?

The announcement is likely to spark off a buying spree – Indians will buy this drug even without a prescription and hoard it. Worse, some may self medicate leading to potential toxicity. There are concerns that large-scale use could lead to anti-malarial resistance.

India has a huge generic market for HCQ but the drug is already out of stock in many online pharmacies. Long term users of chloroquine and HCQ – patients with lupus and rheumatoid arthritis – will find it difficult to procure the drug.

What should have been done?

The drug should have been publicly announced for preventive care and treatment only after a large-scale well designed trial. The World Health Organisation is going to conduct a global trial with four of the most promising treatments for Covid-19.

There is no denying that chloroquine and HCQ will be a game-changer in the management of Covid-19 in India, if large scale trials confirm their effectiveness. The major advantages are the availability and price of the drugs. The other potential drugs used are either too costly or not readily available in India. Toxicity is a pressing concern – the drug use requires monitoring and self medication is dangerous.

Dr Amith Viswanath’s Twitter handle is @avstmd.