FDA Approves Two Oral Antivirals against COVID-19 - India Got One of Them

COVID-19 Pandemic which started in 2019 is probably getting into its last phases as third wave hits India in December 2020-January 2021. Thankfully now we have got two oral drugs against SARS-CoV2 virus which is responible for COVID-19 diseases. So far as per our experience the latest variant of SARS-CoV2, aka Omnicron is the causative agent in the third wave.

America's drug controller FDA (Food and Drug Administration) has approved these two anti-COVID oral antivirals as Emergency Use Authorization (EUA) - Molnupiravir and Paxlovid. 

Details of the both drugs are given in the table. 

	Molnupiravir	Paxlovid
Company	Merck	Pfizer
Generic Name and Formulation	Molnupiravir 200mg, capsules   Available as Capsules (200mg)—40 count bottles.	Nirmatrelvir 150mg; ritonavir 100mg; tablets.   Available as Blister Card—30 tablets divided in 5 daily-dose blister cards. Each blister card contains 4 nirmatrelvir tablets (150mg each) and 2 ritonavir tablets (100mg each). Morning and evening doses indicated on card.
Pharma-cological Class	Nucleoside analogue that inhibits SARS-CoV-2 replication by viral mutagenesis.	SARS-CoV-2 main protease inhibitor + HIV-1 protease inhibitor and CYP3A inhibitor.
Indications	For the treatment of mild to moderate COVID-19 in adults with positive results of direct SARS-CoV-2 viral testing who are at high risk for progressing to severe COVID-19, including hospitalization or death, and for whom alternative COVID-19 treatment options authorized by FDA are not accessible or clinically appropriate. Prior to initiating treatment carefully consider the known and potential risks and benefits.	For the treatment of mild to moderate COVID-19 in adults and pediatric patients 12 years of age and older weighing at least 40kg with positive results of direct SARS-CoV-2 viral testing, and who are at high risk for progression to severe COVID-19, including hospitalization or death.
Limitations	Molnupiravir is not authorized for patients less than 18 years of age; for those requiring hospitalization due to COVID-19; for use longer than 5 consecutive days; or for preexposure or postexposure prophylaxis for prevention of COVID-19.	Paxlovid is not authorized for initiation of treatment in patients requiring hospitalization due to severe or critical COVID-19; for preexposure or postexposure prophylaxis for prevention of COVID-19; or for use longer than 5 consecutive days.
Dosage	Take as soon as possible after a diagnosis of COVID-19 has been made and within 5 days of symptom onset. Swallow whole 800mg (four 200mg capsules) taken orally every 12 hours for 5 days. May be taken with or without food. Safety and efficacy not established in pediatric patients.	Initiate as soon as possible after diagnosis of COVID-19 and within 5 days of symptom onset. Prescriptions should specify the numeric dose of each active ingredient within Paxlovid. Swallow whole. 300mg nirmatrelvir (two 150mg tablets) with 100mg ritonavir (one 100mg tablet), with all 3 tablets taken together twice daily for 5 days. May be taken with or without food. Moderate renal impairment (eGFR ≥30 to <60 mL/min): 150mg nirmatrelvir (one 150 mg tablet) with 100 mg ritonavir (one 100 mg tablet), with both tablets taken together twice daily for 5 days. Severe renal impairment (eGFR <30 mL/min): not recommended. Severe hepatic impairment (Child-Pugh Class C): not recommended. Not authorized for use in pediatric patients younger than 12 years old or weighing less than 40kg.
Warning and Precautions	Embryo-fetal toxicity; not recommended for use during pregnancy. Individuals of childbearing potential should use effective contraception for the duration of treatment and for 4 days after the last dose. Nursing mothers: not recommended during treatment and for 4 days after the last dose. May affect bone and cartilage growth.	Coadministration with drugs highly dependent on CYP3A for clearance and for which elevated concentrations are associated with serious and/or life-threatening reactions. Coadministration with potent CYP3A inducers where significantly reduced nirmatrelvir or ritonavir plasma concentrations may be associated with the potential for loss of virologic response and possible resistance.   Ritonavir has been associated with hepatic transaminase elevations, clinical hepatitis, and jaundice. May lead to a risk of HIV-1 developing resistance to HIV protease inhibitors in patients with uncontrolled or undiagnosed HIV-1 infection.
Adverse Reactions	Most common: Diarrhea, nausea, and dizziness.	Most common: Dysgeusia, diarrhea, hypertension, and myalgia.

 

In India there are 13 pharma companies are working on to launch the 'magic drug' agaist Covid-19 infection as Molnupiravir got DCGI approval. 

• Dr Reddy's Molflu 200mg cap @354 x 2x 5 = 40 cap @1400
• Mankind Pharma's Molulife @Rs 1400
• Cipla - Cipmolu 200mg x 40 cap @Rs 2000
• JB Chemicals - Molunamax 200 x 40 @ 2600
• Zuventus/Emcure - Lizuvira 
• Brinton Pharma - Molviton 200/400mg cap
• Aurobindo Pharma - Molnaflu 
• Lupin - Molnulup
• Natco - Molnunat @ Rs 2000
• Optimus Pharma - Molcovir @ Rs 2500 approx  
• Mylan Pharma - Molnatris, full package Rs 1970

However ICMR is noarma  t convinced enough with Molnupiravir, as the scientists of ICMR says it should not be used in all COVID-19 patients as they could cause serious liver damage. 

In my personal opinion, I am not prescribing it to all patients as Omicron variant of SARS-CoV2 is quite mild in most of the patients. Given antipyretics & other supportive supplements most COVID-19 positive (omnicron) patients recover with time since end of 2021. Molnupiravir might be a game changer if it was launched during the second wave or Delta wave in India. 

Paxlovid is yet to be launched in India. Given Pfizer's stand not to launch their Covid-19 vaccine in India, I doubt it would come to India anytime soon. 

As of now India has approved use of 8 vaccines on EUA - 

1. COVISHIELD - First COVID-19 vaccine India got. It is co-developed by the University of Oxford and British-Swedish company AstraZeneca, the vaccine is manufactured by Serum Institute of India. Most Indians received this vaccine. 
2. COVAXIN - The indigenous 2-dose vaccine, developed by Hyderabad-based Bharat Biotech in collaboration with ICMR and NIV, uses an inactivated virus developed by chemically treating novel coronavirus samples to make them incapable of reproduction.

3. SPUTNIK V - Developed by Russia's Gamaleya Research Institute, the two-dose Sputnik V is a adenovirus vector vaccine. 

4. ZyCoV-D - Ahmedabad-based Zydus Cadila is producing this 3-dose DNA vaccine. 

5. Moderna's mRNA vaccine

6. Johnson and Johnson (single dose adenovirus vector vaccine)

7. CORBEVAX (from Biological-E)

8. COVOVAX (from Novavax, made by Serum Institute of India).