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Antiviral For COVID-19 Suggested by Best Pulmonologist in Jaipur Dr. Nishtha Singh

Antiviral For COVID-19 Suggested by Best Pulmonologist in Jaipur Dr. Nishtha Singh

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Antiviral For COVID-19 Suggested by Best Pulmonologist in Jaipur Dr. Nishtha Singh

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  1. Antiviral The antiviral drug remdesivir was hailed at an early stage of the pandemic as a potential treatment for COVID-19 Dose :- 200 mg (Day 1) 100 mg (Day 2–5)

  2. Side effects a. Liver function test imbalance b. Renal function test imbalance c. Sweating, and shivering. d. Allergic reaction, symptoms may include:- (rash, especially face/tongue/throat) e. Severe dizziness, trouble breathing f. Nausea, & vomiting

  3. Favipiravir (Avigan):Fujifilm • An experimental antiviral drug: viral RNA polymerase inhibitor- • Licensed for use against Influenza in Japan since in Japan since 5 years: • Japanese Government stockpiled 2 million courses for use in seasonal influenza • Not yet FDA approved: but under Trump pressure to speed up

  4. Favipiravir • Used in Ebola trials in Africa: with evidence of some effect • Used in COVID-19 patients in Wuhan and Shenzen: • Shortened fever duration from 4.2 days to 2.5 days in 340 patients and was ‘’clearly effective’’ Chinese Health Ministry (Guardian 18/3/20) • Respiratory improvement in 80 patients in Shenzhen Chen c et al medRxiv (Pre review, posted 27/3/20)

  5. Favipiravir (Avigan):Fujifilm • Oral • Cheap: $ 5 a pill, $ 650 for a course • Safe • Easy to mass produce, off patent: hence generics possible: • China has already stockpiled large numbers of courses • Probably most effective in moderate cases (not severe) • Must be given early

  6. Lopinavir-Ritonavir • Lopinavir : a PI used in HIV • Ritonavir : boosts half life of Lopinavir by inhibiting cytochrome P450 • The combination (Caletra) showed modest in vivo anti-viral activity against SARS-COV(the virus causing SARS) • A single clinical study showed Lopinavir-Ritonavir(400/100mg) reduced ARDS and mortality in SARS Chu CM Thorax 2004 • This is the first drug tried in the RCT in COVID-19 (SARS-C0V-2) Cao B at NEJM 2020

  7. Lopinavir-Ritonavir

  8. Lopinavir-Ritonavir • An urgent randomised clinical trial of efficacy of Lopinavir-ritonavir in severe COVID-19 • From the epicentre of the pandemic in Jin Yan-Tan Hospital, Wuhan • Open label, individually randomized trial Jan 18- Feb 3rd • No placebo due to the emergency of the situation

  9. Inclusion criteria • Hospitalised adults— 1.COVID-19 +ve on RT-PCR 2.Pneumonia confirmed on chest imaging 3.SaO2 < 94% breathing room air or 4.PaO2/FiO2 < 300mg • Randomly assigned in a 1:1 ratio to: Lopinavir-Ritonavir (400/100mg) bid for 14 days + standard Supportive care • VS Standard care alone

  10. 100 patients in each limb the median age of patients was 58 years(49 to 68 years) 60.3% of the patients were men 35% in each group received steroids

  11. Lopinavir - Ritonavir: Results • Unfortunately trial results disappointing - - • No benefit in time to clinical improvement - - • No discernible effect on viral load - - • Slightly lower 28 day mortality in the Lopinavir-Ritonavir group: • 19% L-R vs 25% placebo (p =0.32) • In ordinary days insignificant: but in extra-ordinary days:6% drop ok? • Overall negative study: small numbers, standard care group sicker

  12. Editorial comments • Remarkable that the trial began days after the virus was identified • The investors appropriately prioritized speed designing a trial that rapidly gave answers • This was a heroic effort as HCWs in Hubei were also providing patient care in an overwhelming epidemic and were themselves high risk for development to disease • Lindsey Baden and Eric Rubin, Editorial NEJM

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