Even as the debate rages on about the benefits and side-effects of using the anti-viral drug Favipiravir, the national capital’s first COVID-19 only facility Lok Nayak Hospital has decided to discontinue the drug among its patients.
In a meeting called by LNH director professor of medicine Dr MK Daga on June 29, 2020, to discuss the use of newer drugs for COVID-19 treatment at the hospital, it was decided to discontinue the use of Favipiravir at the hospital. According to the observations made by the doctors of the hospital, the drug was being given for mild and moderate cases. The side-effects of the drug include decreased appetite, nausea, diarrhoea, increased uric acid levels, decreased counts of white blood cells that help heal damaged tissues (neutrophil counts) and increased liver enzymes (AST/ALT levels).
During the use of the drug, it was observed that the heart muscle took longer than normal to recharge between beats (QT prolongation). The doctors were worried about the Uric acid levels too. All of these observations ensured that the committee recommended that Favipiravir should not be used for treatment in the hospital. The doctors who attended the meeting included Dr Urmila Jhamb, Dr Munisha Agarwal and the COVID-19 nodal officer Dr Sandeep Garg. The recommendations of the committee were approved by the hospital’s medical director Dr Suresh Kumar.
Favipiravir is an oral antiviral approved for the treatment of influenza in Japan since 2014 and is known to block a viral enzyme in RNA polymerase, which is necessary for viral replication. This means that the virus is prevented from replicating. In India, Glenmark Pharmaceuticals secured government approval for the manufacturing and marketing of the drug Favipiravir under the brand name FabiFlu to treat mild to moderate COVID-19 cases. The approval was granted under an accelerated process in the third week of June after the recommendation of special Subject Expert Committee (SEC) on Covid-19. The company has been asked to submit a copy of the report of the clinical trials within three months. Favipiravir has been used in the past for treating influenza and Ebola.
According to Glenmark, the drug showed promise in clinical trials when it was given to 150 patients with mild and moderate COVID-19 cases. All of the patients had been hospitalised for COVID-19 treatment and the drug was included in their medical dosages. The research for the drug was done by Glenmark in Navi Mumbai and the drug is being manufactured at its Ankleshwar plant in Gujarat.
The company also cautioned against its usage on patients with severe renal, hepatic impairment, pregnant and lactating women. Its usage is restricted on patient with history of abnormalities in metabolism of uric acid or if they have gout. The company has priced it at ₹3,500 for a pack of 34 tablets, making it a highly priced drug during the pandemic.
Despite the uncertainty, Maharashtra’s Brihanmumbai Municipal Corporation announced that it would buy 27 lakh tablets of Favipiravir at the price of Rs 80 per tablet. This purchase will cost BMC around ₹21 crore.
One of the remarks made by the LN Hospital committee was that there was less data available on the effectiveness of Favipiravir. In fact, the drug has got approval for usage only in India, China and Russia. In the US, researchers at Stanford Medicine will begin a clinical trial on July 6 to evaluate if oral dosages of Favipiravir will reduce symptoms of COVID-19. It is yet to be approved by the US Food and Drug Administration (FDA).
The hospital administration decided to side-step the issue gingerly. “It’s not that we have not recommended it inclusion in the treatment protocol, Lok Nayak Hospital gets only moderate to severe cases. There are no mild cases in the hospital. That is why we have not recommended. We have recommended all the drugs which have been approved for treatment,” said Suresh Kumar, the LN Hospital medical director.
Adding to this was the nodal officer Dr Sandeep Garg. “There are better drugs to treat Covid-19 patients. Moreover, LN Hospital does not get mild cases,” reiterated Garg.
Moreover, it is an extremely expensive drug as a full course will cost ₹25,000. “Everyone is saying a tablet costs only Rs 103 for 200 mg. But, a patient has to be given 1,800 mg (18 tablets per day) twice on the first day. Then subsequently the patient has to be given 800 mg (8 tablets per day) twice in a day for seven days and if the patient has a moderate case of Covid-19, it has to be given for 14 days. A full course costs ₹25,000. There are better treatment protocols available,” underscored Dr Kush Sharma, a senior resident working in the LN Hospital’s intensive care unit.
LN Hospital’s recommendation comes at a time when even though Drugs Controller General of India (DGCI) had approved Favipiravir for restricted medical use, the drug was not part of the treatment protocol recommended by Indian Council of Medical Research (ICMR), according to reports. ICMR experts were not convinced about the drug.
The LN Hospital committee approved the use of three other drugs – Remdesivir, Tocilizumab and Ivermectin – and plasma therapy in the treatment of COVID-19.
The four-member committee stated that Remdesivir could be used for moderate cases of COVID-19 if the patient shows no response to steroids and to oxygen therapy. They cautioned against using Hydroxychloroquine (HCQS) along with Remdesivir as it interfered with Remdesivir action. Even this antiviral medication caused nausea, vomiting, constipation and high liver enzymes. They have recommended caution while using the drug on renal patients, children, pregnant and lactating women.
The immunosuppressive drug Tocilizumab can be used on moderate to severe COVID-19 patients, especially if there is a hyperactive immune response (cytokine storm) in the body. The committee has recommended precautions while using the drug on TB patients, people with systematic bacterial and fungal infection and those on other immunosuppressive therapy such as for cancer treatment. The doctors have warned against using this drug if tests show that there are heightened levels of liver enzymes.
The committee acknowledges that though Ivermectin has shown only laboratory evidence as an inhibitor of the COVID-19 causative virus, it should be considered for hospitalised patients because it is a cheap drug, easily available and is known to be safer than other drugs. Its side effects are only fever and skin rash. This drug, which has been approved by the US FDA for parasitic infections, could help in limiting the viral load and prevent severe disease progression, according to the doctors at LN Hospital.
Plasma therapy will be continued in the hospital though the list of those who will be excluded from the therapy is longer than those who will be included. People with cardio-pulmonary comorbid diseases, liver disease patients, chronic kidney patients, patients younger than 18 and older than 60, those will morbid obesity and pregnant patients will be excluded from the therapy. Only those patients with severe COVID-19 infections within seven days of the onset of the disease will be included in the therapy.
These recommendations have come when Delhi registered 2,373 fresh coronavirus cases on July 2. It increased the total tally of those infected in the capital city to 92,175 and the death toll due to the disease stood at 2,864. On July 2, the Delhi Chief Minister Arvind Kejriwal had announced the launch of the plasma bank for the collection of plasma for the treatment of COVID-19.