India Cuts Use of Remdesivir, Tocilizumab, Multivitamins, Steroids in Covid-19 Treatment

India has cut down on the use of the experimental drug Remdesivir and immunosuppressive drug Tocilizumab for the treatment of Covid-19.

On Monday, the Indian Council of Medical Research (ICMR), the country’s apex medical research body, released the new treatment guidelines for the management of Covid-19.

According to the new guidelines, Remdesivir may be considered only in patients who have completed 10 days since the start of the symptoms and require supplemental oxygen.

However, it has clarified that the drug cannot be given to patients who are on ventilator or on extracorporeal membrane oxygenation (ECMO), a treatment that uses a pump to circulate blood through an artificial lung back into the bloodstream of a very ill baby.

While it states that doctors can “consider Remdesivir for five days to treat hospitalised patients with Covid-19”, it also mentions that “no evidence of benefit for treatment more than five days”.

Designed by AIIMS and ICMR-led Covid-19 National Task Force, the latest protocol, apart from curtailing the role of controversial drug Remdesivir, has waived off the use of multivitamin pills which was earlier advised for the treatment of mild cases.

Under the management of mild Covid disease, the list of “must-do” activities includes hydration, anti-pyretics and anti-tussive, removing the need to pop multivitamins.

This means that when a patient is suffering mild symptoms with no shortness of breath or low oxygen in blood (SpO2), they must keep themselves hydrated, consume anti-fever medicines and medicines to suppress cough.

Use of Steroids Discouraged

For moderate cases, the protocol clarifies “there is no evidence for benefit for injectable steroids” in patients who are not requiring oxygen supplementation, or on continuation after discharge. The move is triggered by the increase in cases of black fungus after the second wave due to the overuse of steroids.

A total of 51,775 cases of mucormycosis or ‘Black Fungus’ had been reported till November 29, Union Health Minister Mansukh Mandaviya informed the Lok Sabha in December.

Discouraging the overuse of steroids, the protocol for both moderate and severe patients notes that “anti-inflammatory or immunomodulatory therapy (such as steroids) can have risk of secondary infection such as invasive mucormycosis when used too early, at higher dose or for longer than required.”

Additions in the New Guidelines

The latest guidelines include “blood sugar” as an additional test under the laboratory monitoring protocol for both severe and moderate patients.

Earlier, the protocol suggested monitoring of “CRP and D-dimer, complete blood count (CBC), kidney function test (KFT), liver function test (LFT) and IL-6 levels”.

It also suggests that if cough, in mild cases, persists for more than two to three weeks, investigate for tuberculosis and other conditions. The protocol also added people with “active tuberculosis” under the category of high risk for severe disease or mortality.

For the mild, the new treatment does not promote the prescription of multivitamins.

Change in Tocilizumab Guidelines

It also mentions that Tocilizumab can be considered for patients who meet five criteria, including that the patient should not have active tuberculosis, fungal or any systemic bacterial infection.

The immunosuppressant drug can only be given to patients who are on oxygen therapy or on ventilators but not responding to steroids. Also, the inflammatory markers should be significantly raised. But the drug should preferably be given along steroids, it mentions.

The guidelines also emphasise that in case of administration of the drug, long-term follow up should be done for secondary infections such as reactivation of TB or flaring of herpes.

Earlier, the guidelines included a wider set of patients who could be given the drug as it can be given to people with “presence of severe disease” without mentioning any criteria for patient selection.

Carefully Selected Subset of Patients

According to experts treating Covid-19 patients in hospitals across India, the latest guidelines are “evidence-based”, especially on reducing the role of Tocilizumab. However, they pointed out that Remdesivir should be on its way out as several trials have already proved that the drug is of no use in Covid-19.

“Remdesivir has been continued but with lots of caveats,” said Sumit Ray, head of department of Critical Care Medicine at Holy Family Hospital. “The ministry is playing safe. The WHO guidelines have weak recommendations against its use. The time for Remdesivir is running out. It remains a drug in search of a disease. The role of antivirals in a rapidly replicating respiratory virus is going to be very questionable.”

Solidarity trial has not approved Remdesivir, experts said. The trial concluded that Remdesivir, Hydroxychloroquine, Lopinavir, and interferon regimens had little or no effect on hospitalised patients with Covid-19, as indicated by overall mortality, initiation of ventilation, and duration of hospital stay.

“Death occurred in 301 of 2,743 patients receiving Remdesivir and in 303 of 2,708 receiving its control, hence no difference was observed,” said Dr SP Kalantri, Professor of Medicine, Mahatma Gandhi Institute of Medical Sciences, Maharashtra while suggesting that “we also need to ask what additional advantage does Remdesivir offer in hospitalised hypoxic patients who are already on dexamethasone — a steroid that has been shown to save lives in critically ill Covid patients.”

According to Dr Yatin Mehta, chairman, Institute of Critical Care and Anaesthesiology, Medanta, the move to retain Remdesivir makes sense.

“A new study on Remdesivir has shown significant benefit when given to patients at home for three days. However, these guidelines might have been formed prior to the release of the latest study,” he said, hinting that if useful, Remdesivir may also be considered for use in home settings.

India’s clamour for Remdesivir has been a misfit against the World Health Organization (WHO)’s advice. Earlier, WHO had said that there is no evidence to suggest that the antiviral drug can effectively treat Covid-19 patients.

However, guidelines of Tocilizumab are fine, Mehta said.

Ray from Holy Family Hospital emphasised that “the role for Tocilizumab lies in an extremely small carefully chosen subset”.

The problem with India is the clinicians’ ability to make those judgements. Sometimes, he said, these judgements are not well informed due to a lack of continuing medical education to upgrade one’s knowledge of disease processes.

“The side effects of immunosuppression with either high dose steroids or Tocilizumab are very serious, thus, patient selection has to be carefully evaluated, so that the benefits have a fair chance of outweighing the risks.”

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