The national regulatory body for Indian pharmaceuticals and medical devices- Central Drugs Standard Control Organisation (CDSCO) has provided approval as part of restricted & emergency use authorization for the below two medicines considering the unmet medical need for treatment of COVID-19 infected patients-

1. Favipiravir Tablets for mild to moderate COVID-19 infection subject to various conditions and restrictions
2. Remdesivir Injectable Formulations for treatment of patients with severe COVID-19 infection

 

Favipiravir (FabiFlu)

Favipiravir is an antiviral medication chemically it is a pyrazinecarboxamide derivative which is used in the treatment of influenza. This molecule is developed and manufactured by Toyama Chemical (Avigan) and it became generic in the year 2019. This acts by selective inhibition of viral RNA-dependent RNA polymerase, thereby inhibiting the activity of viral replication to reduce the viral load. With the early use of antiviral drugs, a high rate of viral replication can be controlled.

In the midst of COVID-19 pandemic, where the no effective drugs have not developed yet, favipiravir has shown efficacy (80%) in mild to moderate coronavirus patients during clinical trial (a clinical study conducted by Glenmark among 90 mild and 60 moderate COVID-19 patients across 11 sites in India)

On 19-Jun-2020, Glenmark Pharmaceuticals, the India’s generic manufacturer of favipiravir with brand name of FabiFlu has received emergency use authorization (EUA) from the Indian regulatory authority-Drug Controller General of India (DCGI) to manufacture and market in the India.

This medicine is available in oral formulations (Tablet form) which costs about Rs 3,500 for a pack of 34 tablets (Rs 103 per tablet) and with the recommended dosage of 200 mg X 9 tablets on the day one and 200 mg X 4 tablets per day for 14 days of the treatment. This is the first oral antiviral drug in India to treat COVID -19 patients under emergency use authorization. Company stated that Favipiravir can be used for COVID-19 patients with underlying medical conditions such as diabetes and heart disease with mild to moderate corona virus symptoms.

However, the efficacy and safety of Favipiravir in treating coronavirus infected patients is not well established yet! and it got approval in India under emergency use authorization category due to exponential increase in the number of infected patients every day.

Remdesivir (GS-5734)

Remdesivir (GS-5734) is being developed by Gilead Sciences, an American Innovator biopharmaceutical company based in California with a primary therapeutic focus in antiviral medicines. Remdesivir is an antiviral drug (broad spectrum) under clinical trial investigation for the treatment of Ebola virus infection and COVID-19, a coronavirus disease. Remdesivir gained public attention due to publication of some of its clinical study results globally for the treatment of patients with COVID-19.

Gilead has provided approval under voluntary licensing agreements to the below companies for Remdesivir manufacture & distribution in 127 countries-

1. Cipla Ltd.
2. Reddy’s Laboratories Ltd
3. Eva Pharma
4. Ferozsons Laboratories
5. Hetero Labs Ltd
6. Jubilant Lifesciences
7. Mylan
8. Syngene, a Biocon company
9. Zydus Cadila Healthcare Ltd.

As per Licence agreement:

• The above listed companies have right to receive a technology transfer for remdesivir manufacturing process from Gilead which would enable these to scale up production more quickly.
• The above listed companies can set their own prices for the generic remdesivir.
• The agreement is royalty free (for the licensees) till, the development of a pharmaceutical product (other than remdesivir) effective in treatment or vaccine effective in preventing COVID-19 is available or approved, OR when the World Health Organization (WHO) announces the end of this Public Health Emergency of International Concern regarding COVID-19.

On 01-Jun-2020, Gilead received approval from CDSCO for import and marketing the remdesivir drug in India.

On 20-Jun-2020, to ensure early access of this remdesivir for treatment of severe COVID patients in the country under the Restricted Emergency Use, CDSCO has granted permission to Cipla Ltd and Hetero Drugs (Two of the above listed 9 companies) to manufacture and market the same injectable formulations of the remdesivir drug to the indigenous manufacturers for the COVID-19 treatment with the same restrictions and conditions for use as stipulated for GILEAD’s innovator product.

Obligation:

The patients/patient’s representative should sign an informed consent (an undertaking before consuming the medicine) before using remdesivir or favipiravir as part of treatment for corona virus infection.

Individual Benefit-Risk Assessment:

Since these two drugs are not originally developed for COVID-19 treatment and their efficacy, safety profiles were not yet established completely, it is wise to strictly monitor the behaviour of these two medicines during their presence in this time of coronavirus pandemic. Especially, the possibility of identification of new adverse reactions, signals and risks are high during their use. Physicians and other health care professionals are recommended to assess the individual benefit risk balance based on the patient’s current underlying medical conditions, concurrent medications, medical history, special populations like pregnant women, paediatric and geriatric patients and other risk factors which could have impact on the overall benefit risk profile of medicine to use.

Voluntary Medicine Side Effect Reporting:

In order the hasten the establishment of safety profile for these potential medicines for COVID-19 treatment, All health care professionals and consumers are encouraged to be cautious, observe and watch and undesirable experiences (events or reactions) after drug administration. When any signs or symptoms of any adverse drug event or reaction(s) are observed for patient, it is strongly recommended to report the same to national regulatory body.

Early identification of new adverse drug reactions/concerns/potential medication errors could lead to the early implementation of minimization measures for the same thereby improving the patient safety and overall public health.

Channels of Side effects reporting to PvPI in India:

PvPI (Pharmacovigilance Programme of India)-which is actively conducting postmarketing drug safety surveillance in India is collecting all the case reports pertaining to medicinal products across the India. Below are the available channels for reporting side effects PvPI

• PvPI Helpline No.1800 180 3024 (Timing: 9.00 AM to 5.30 PM (Monday to Friday))
• Android Mobile App “ADR PvPI” which is freely available from Google Play Store.
• The Adverse Events/Adverse Drug Reaction may be reported to nearest Adverse Drug Reaction Monitoring Centers (AMCs), the list of AMCs is available on the website of Indian Pharmacopoeia Commission- http://www.ipc.gov.in/images/LIST_OF_270_AMC_UNDER_PvPI.pdf