Antivirals Recommended by Dr Nishtha Singh Saans doctor in Jaipur

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Antivirals

• 1. REMDESIVIR (Gilead)
• 2. FAVIPRAVIR (Fujifilm)
• 3. LOPINAVIR-RITONAVIR (Abbvie)

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Remdesvir recognized as a promising antiviral
drug with in-vivo inhibitory
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What works and what doesnt ?

• 1.ANTI-VIRALS
• 2.ANTI-INFLAMMATORY AGENTS
• 3.CHLOROQUINE /HYDROCHLOROQUINE
• 4.HUMAN CONVALESCENT PLASMA
• 5.VACCINES
• 6.AND WHAT DOESNT WORK ?

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Remdesivir

• A 10 year old IV anti- viral discovered by Gilead
  Sciences
• Shown then to be effective against SARS, MERS,
  some Corona viruses
• First used in clinical trials against Ebola 500
  cases (did not prove effective)
• Currently to be fast- tracked and tested in 5
  COVID-19 clinical trials set up at breakneck
  speed initial results soon
• Safe transient elevation in transaminases
  reported in phase 1 studies
• Used (compassionate) in the first COVID-19 case
  reported in the USA

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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

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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)

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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

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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

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Lopinavir-Ritonavir
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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
  

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Inclusion criteria

• Hospitalised adults
• 1.COVID-19 ve on
  RT-PCR
• 2.Pneumonia
  confirmed on chest imaging
• 3.SaO2 lt 94
  breathing room air or
• 4.PaO2/FiO2 lt 300mg
• Randomly assigned in a 11 ratio to
• Lopinavir-Ritonavir (400/100mg) bid for 14
  days standard Supportive care
• VS
• Standard care alone

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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
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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 days6 drop ok?
• Overall negative study small numbers, standard
  care group sicker

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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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Anti inflammatories

• 1) TOCILIZUMAB (Actemra)
• 2)SARILUMAB(Kevzara)
• 3)HYDROXYCHLOROQUINE