Will indomethacin be the rescue drug for Covid-19 in India?

Dr Rajan Ravichandran | Updated on July 08, 2020

It’s an old, inexpensive anti-inflammatory drug that can address cough, a key cause of infection spread

Covid-19 has been spreading rapidly in India, with more than 7 lakh cases till date and related deaths of more than 19,000. Still, the disease has not reached the peak and there is concern over the increasing mortality rate. It is essential that we reduce the spread and hospitalisation, which in turn can ease the strain on the healthcare system.

Indomethacin appears to be a tailor-made drug for that purpose. It is a very old anti-inflammatory drug patented in1960 for the treatment of rheumatoid arthritis. It reduces the production of prostaglandins by inhibiting enzyme cyclooxygenase in the body (COX 1 and COX2). While COX 2 is concerned with the cytokine storm (inflammatory chemicals) seen with infections, COX 1 is concerned with kidney function and stomach secretions.

An interesting action of indomethacin is its antiviral properties. In 2006, in the SARS epidemic, it was shown to act against the coronavirus in dogs. In 2007, it was granted a patent in the US for broad-spectrum anti-viral properties. It has been shown effective against the CMV virus and the human vesicular virus, in 2020.

In monkeys, it has been effective against the corona-2 virus. Of course, the anti viral properties for coronavirus have not been tried in humans. Another interesting effect of the drug is the prevention of lung clots in animals dying of sepsis and multi organ failure.

What is the clinical data?

Dr Jonathan Leibowitz from New York tried it in 60 patients of Covid-19 with 90 per cent showing prompt recovery. One of the effects he described is a dramatic improvement in cough. This observation is significant since cough is one of the main reasons for the spread of the disease.

There is an ongoing trial in Arizona, USA, in combination with other drugs and in Iran for indomethacin alone. Currently, paracetamol is used widely for symptomatic treatment in Covid. The anti-inflammatory properties of indomethacin make it a much superior drug in this context.

If the drug is so promising why is it not used widely? What are the drawbacks?

First and foremost the drug is very old. So many young physicians are not familiar with its use and think it is toxic. Secondly, it is very cheap, which is both an advantage and a disadvantage. The main side-effects are gastritis and reduced kidney function. Both are dose-related, occurring in doses of more than 200 mg per day or at least 100 mg per day. These are reversible if the drug is stopped.

The gastritis is also temporary and disappears with continued usage, which is called gastric adaptation. It is also preventable when used with proton pump inhibitors (anti-acid drugs). The reduction in kidney function is seen mainly in critical patients and with doses of more than 150 mg per day and for long. Short-term (five to seven days) use with doses of less than 75 mg per day is very safe.

So how can we use this as a rescue drug in India?

Like our national programmes for diseases like malaria, anaemia and filariasis, following house-to-house visits in hotspot areas with regular testing can help. Indomethacin 25 mg twice a day for five days can be given to all cases with fever and even close contacts (costs ₹50 for a course of five days) along with omeprazole 20 mg (anti-acid drug).

Since the drug cuts off cough, the spread will come down. Hospitalisation is also likely to come down since patients become rapidly asymptomatic. Only sick patients will need to be hospitalised and considered for expensive treatment options. Stable patients in hospitals can also be given indomethacin to control symptoms and reduce the stay. The patients who cannot take indomethacin are those who are allergic to it or have had recent heart attacks or stomach bleeding.

The drug can be used even in pregnancy till the last few weeks. The role of indomethacin in critical patients requires weighing the risk benefit ratio, haemodynamic stability and other parameters.

Treatment alone cannot be an answer to the Covid problem; however, it will build confidence in people. Social distancing and wearing of masks should continue. Hopefully, a vaccine will be rolled out or the virus will mutate in the near future, getting India out of the crisis.

The writer is Director, Department of Nephrology, MIOT Hospital, Chennai

Published on July 08, 2020

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