Indomethacin for early covid-19

Article written by Christine Clark

Indomethacin reduces the severity and duration of covid-19 symptoms and the need for hospital admissions

There is mounting evidence to support the use of indomethacin to control covid-19 symptoms. Since we reported the experience of physicians in New York with the use of indomethacin in early covid-19, further reports and real world findings have added weight to calls for a randomised controlled trial to determine the effectiveness of the drug in this context.     

Here is the story so far:

Indomethacin is a non-steroidal anti-inflammatory drug (NSAID) that has been used for the past 50 years in millions of patients. It has analgesic and anti-pyretic effects. Indomethacin is now a generic drug that is widely available in most countries at low cost. In the United Kingdom it is a prescription-only medicine (POM).

It has been prescribed by doctors in New York for numerous patients with early covid-19 symptoms, with good results in over 60 patients. They found that patients obtained rapid relief from cough, chest pain and headache, sometimes after as little as two doses.¹

Indomethacin has been prescribed by a nephrologist in India to a series of 17 high-risk patients with early covid-19 symptoms (some of whom were immunocompromised) again with good results.²

A further trial of indomethacin in early covid-19 in more than 100 patients is now nearing completion in India. Clinicians in India report the drug has been used successfully in more than 1000 patients with early covid-19 symptoms.

The reported benefits of indomethacin – relief of cough, chest pain and headache, are achieved with low-moderate doses (25-50mg, two or three times a day) that are within the licensed dose range for indomethacin.  Treatment is usually only required for a few days. 

A recent study identified nearly 740,000 patients with documented SARS-CoV-2 infection. Some 244 of these were taking indomethacin and 474 were taking celecoxib (a NSAID that, unlike indomethacin, does not inhibit prostaglandin E synthase 2 (PGES-2)). A comparison of matched groups showed that indomethacin users were less likely than celecoxib users to require hospitalisation or inpatient services (Odds ratio (OR) 0.25; 95% CI 0.08 – 0.76).³  

The beneficial effects reported appear to relate to indomethacin and not to other NSAIDs, such as ibuprofen. Indomethacin was shown to have anti-viral activity against SARS in 2006 in the wake of the SARS-CoV outbreak.⁴ It was subsequently shown to be active against SARS-CoV-2 in vitro and against canine coronavirus in vivo.⁵ Importantly, the antiviral effects were seen at normal anti-inflammatory dose levels.

The evidence for the use of indomethacin for symptom control in patients with early covid-19 is now so strong that we can no longer afford to ignore it.

The use of indomethacin (25 – 50 mg twice a day) early in the course of covid-19 infection can reduce the severity and duration of covid symptoms and reduce the need for hospitalisation.

Much covid research has been directed at management of patients who are critically ill with covid-19; this drug offers the opportunity for upstream prevention of serious illness, at a very modest cost (£1.42 for 28 x 25mg capsules). Moreover, although not specifically authorised for use in covid-19, it is, like other NSAIDs, licensed for use in musculoskeletal pain and fever and could therefore be prescribed by general practitioners or prescribing pharmacists immediately.  

If the drug were put into routine use there could be health benefits and considerable saving of NHS resources. This could result in an easing of restrictions and a move towards normality.

References

1. Rothstein R, Leibowtiz J, Benjamin A, Clark C. Rapid Response: Re: Non-steroidal anti-inflammatory drugs and covid-19. https://www.bmj.com/content/368/bmj.m1185/rr-3

2. Ravichandran R, Srinivasan S, Clark C. Low dose indomethacin for symptomatic treatment of covid-19. Int J Med Rev Case Rep. 2020; 4(Reports in Microbiology, Infectious Diseases and Dermatology): 69-70doi: 10.5455/IJMRCR.LOW-DOSE-INDOMETHACIN. doi:10.5455/IJMRCR.LOW-DOSE-INDOMETHACIN

3. Gordon DE et al.  Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms. Cite as: Science

10.1126/science.abe9403 (2020).

4. Amici C et al.  Indomethacin has potent antiviral activity against SARS coronavirus. Antivir Ther 2006; 11: 1021–1030

5. Xu et al Indomethacin has a potent antiviral activity against SARS CoV-2 in vitro and canine coronavirus in vivo  April 2020 https://doi.org/10.1101/2020.04.01.017624.

CMC 21.10.20