Remdesivir used for covid 19

1. REMDESIVIR USED FOR COVID-19
Mr. Sagar Kishor Savale
4/25/2021
Mr. Sagar Kishor Savale
Remdesivir USED for COVID-19
[Process Development Scientist]
India
Remdesivir-COVID-19
Remdesivir, sold under the brand name Veklury, is a broad-spectrum antiviral medication
developed by the biopharmaceutical company Gilead Sciences. It is administered via
injection into a vein. During the COVID-19 pandemic, remdesivir was approved or
authorized for emergency use to treat COVID‑19 in around 50 countries. Updated
guidelines from the World Health Organization in November 2020 include a conditional
recommendation against the use of remdesivir for the treatment of COVID-19.
Remdesivir is a prodrug that is intended to allow intracellular delivery of GS-441524
monophosphate and subsequent biotransformation into GS-441524 triphosphate, a
ribonucleotide analogue inhibitor of viral RNA polymerase.
In November 2020, the World Health Organization (WHO) updated its guideline on
therapeutics for COVID-19 to include a conditional recommendation against the use of
remdesivir, triggered by results from the WHO Solidarity trial. The European Medicines
Agency announced that they will evaluate new data to see if a revision to the authorization
of remdesivir is needed.
In the European Union, remdesivir is indicated for the treatment of coronavirus disease
2019 (COVID‑19) in adults and adolescents (aged twelve years and older with body weight
at least 40 kilograms (88 lb)) with pneumonia requiring supplemental oxygen.
In the United States, remdesivir is indicated for use in adults and adolescents (aged twelve
years and older with body weight at least 40 kilograms (88 lb)) for the treatment of

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COVID‑19 requiring hospitalization. In November 2020, the FDA issued an emergency
use authorization (EUA) for the combination of baricitinib with remdesivir, for the
treatment of suspected or laboratory confirmed COVID-19 in hospitalized people two years
of age or older requiring supplemental oxygen, invasive mechanical ventilation, or
extracorporeal membrane oxygenation (ECMO).
How Should This Medicine Be Used
Remdesivir comes as a solution (liquid) and as a powder to be mixed with liquid and
infused (injected slowly) into a vein over 30 to 120 minutes by a doctor or nurse in a
hospital. It is usually given once daily for 5 to 10 days. The length of your treatment
depends on how well your body responds to the medication.
Remdesivir injection may cause serious reactions during and after the infusion of the
medication. A doctor or nurse will monitor you carefully while you are receiving the
medication. Tell your doctor or nurse immediately if you experience any of the following
symptoms during or after the infusion: chills or shivering; nausea; vomiting; sweating;
dizziness upon standing up; rash; wheezing or shortness of breath; abnormally fast or slow
heartbeat; or swelling of the face, throat, tongue, lips, or eyes. Your doctor may need to
slow down your infusion or stop your treatment if you experience these side effects.
The FDA has approved an Emergency Use Authorization (EUA) to allow children
weighing 8 pounds (3.5 kg) to less than 88 pounds (40 kg) or children less than 12 years of
age weighing at least 8 pounds (3.5 kg) who are hospitalized with severe COVID-19 to
receive remdesivir.

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Special Precautions- Before Receiving Remdesivir
1. Tell your doctor and pharmacist if you are allergic to remdesivir, any other
medications, or any of the ingredients in remdesivir injection. Ask your pharmacist
for a list of the ingredients.
2. Tell your doctor and pharmacist what other prescription and nonprescription
medications, vitamins, nutritional supplements, and herbal products you are taking
or plan to take. Be sure to mention any of the following: chloroquine or
hydroxychloroquine (Plaquenil). Your doctor may need to change the doses of your
medications or monitor you carefully for side effects.
3. Tell your doctor if you have or have ever had liver or kidney disease.
4. Tell your doctor if you are pregnant, plan to become pregnant, or are breastfeeding.
In Case Of Emergency/Overdose
In case of overdose, call the poison control helpline at 1-800-222-1222.
Information is also available online at https://www.poisonhelp.org/help
[https://www.poisonhelp.org/help]. If the victim has collapsed, had a seizure,
has trouble breathing, or can't be awakened, immediately call emergency
services at 911.
Brand Names: Veklury, GS-5734.

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Mechanism Of Action
As an adenosine nucleoside triphosphate analog (GS-443902), the active metabolite of
remdesivir interferes with the action of viral RNA-dependent RNA polymerase and evades
proofreading by viral exoribonuclease (ExoN), causing a decrease in viral RNA
production. In some viruses such as the respiratory syncytial virus it causes the RNA-
dependent RNA polymerases to pause, but its predominant effect (as in Ebola) is to induce
an irreversible chain termination. Unlike with many other chain terminators, this is not
mediated by preventing addition of the immediately subsequent nucleotide, but is instead
delayed, occurring after five additional bases have been added to the growing RNA
chain.[36] For the RNA-Dependent RNA Polymerase of MERS-CoV, SARS-CoV-1, and
SARS-CoV-2 arrest of RNA synthesis occurs after incorporation of three additional
nucleotides. Hence, remdesivir is classified as a direct-acting antiviral agent that works as
a delayed chain terminator.
Interactions
Remdesivir is at least partially metabolized by the cytochrome P450 enzymes CYP2C8,
CYP2D6, and CYP3A4. Blood plasma concentrations of remdesivir are expected to
decrease if it is administered together with cytochrome P450 inducers such as rifampicin,
carbamazepine, phenobarbital, phenytoin, primidone. Using chloroquine or
hydroxychloroquine with remdesivir may reduce the antiviral activity of remdesivir.
Coadministration of remdesivir and chloroquine phosphate or hydroxychloroquine sulfate
is not recommended based on in vitro data demonstrating an antagonistic effect of
chloroquine on the intracellular metabolic activation and antiviral activity of remdesivir.

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Pharmacology
Remdesivir is a ProTide (Prodrug of nucleoTide). It is able to diffuse into cells where it is
converted to GS-441524 mono-phosphate via the actions of esterases (CES1 and CTSA)
and a phosphoamidase (HINT1); this in turn is further phosphorylated to its active
metabolite triphosphate by nucleoside-phosphate kinases. This pathway of bioactivation is
meant to occur intracellularly, but a substantial amount of remdesivir is prematurely
hydrolyzed in plasma, with GS-441524 being the major metabolite in plasma, and the only
metabolite remaining two hours after dosing.
Side Effects
The most common adverse effects in people treated with remdesivir were respiratory
failure and blood biomarkers of organ impairment, including low albumin, low potassium,
low count of red blood cells, low count of thrombocytes, and elevated bilirubin (jaundice).
Other reported adverse effects include gastrointestinal distress, elevated transaminase
levels in the blood (liver enzymes), infusion site reactions, and electrocardiogram
abnormalities. Remdesivir may cause infusion‐ related reactions, including low blood
pressure, nausea, vomiting, sweating or shivering.
Mr. Sagar Kishor Savale
[Process Development Scientist]
M. 8830658405