Update 3

Remdesivir

Remdesivir is an investigational nucleotide analog with broad-spectrum

antiviral activity. The limited preclinical data on Remdesivir in MERS and

SARS indicate that Remdesivir may have potential activity against

coronavirus disease 2019 (COVID-19).

Remdesivir is an experimental medicine that does not have established

safety or efficacy for the treatment of any condition, but it has been used as

part of emergency usage in the treatment of ongoing COVID-19 infection.

Adult Dosage

Coronavirus disease 2019

MoHFW India regimen (EUA, June 2020)

● Patients with moderate disease requiring oxygen supplementation

IV

○ Loading dose: 200 mg on day 1

○ Maintenance dose: 100 mg OD, for 4 days
○ Dosage is contraindicated in patients with severe hepatic or renal
impairment, patients with serum AST/ALT level >5 times the
upper limit of the normal range (ULN), and pregnant or lactating
females.
NOTE Clinical criteria for moderate disease, as per MoHFW India, is patients

having pneumonia with no signs of severe disease (respiratory rate

15–30/min, SpO2 90%–94%).

1 Updated: 05/05/2020
 Or

FDA regimen (EUA, May 2020)

● Patients with severe disease requiring invasive mechanical ventilation

and/or requiring extracorporeal membrane oxygenation (ECMO)
IV

○ Loading dose: 200 mg OD, infused over 30–120 minutes on day

1
○ Maintenance dose: 100 mg OD, for 9 days
○ Treatment should not be initiated in patients with serum ALT
level ≥5 times ULN at baseline
● Patients with severe disease not requiring invasive mechanical
ventilation and/or ECMO
IV

○ Loading dose: 200 mg OD, on day 1

○ Maintenance dose: 100 mg OD, for 4 days
○ If clinical improvement is not demonstrated, treatment may be
extended for up to 5 additional days (i.e. up to a total of 10
days).
○ Treatment should not be initiated in patients with serum ALT
level ≥5 times ULN at baseline
NOTE Clinical criteria for severe disease, as per FDA, is SpO2 ≤94% on

ambient air, requiring supplemental oxygen, mechanical ventilation, or

EMCO.

Pediatric Dosage

Coronavirus disease 2019

MoHFW India regimen (EUA, June 2020)

● Patients of age >12 years with moderate disease requiring oxygen

supplementation

1 Updated: 05/05/2020
 IV

○ Loading dose: 200 mg on day 1

○ Maintenance dose: 100 mg OD, for 4 days
○ Dosage is contraindicated in patients with severe hepatic or renal
impairment, patients with serum AST/ALT level >5 times ULN,
and in pregnant or lactating females.
NOTE Clinical criteria for moderate disease, as per MoHFW India, is patients

having pneumonia with no signs of severe disease (respiratory rate

15–30/min, SpO2 90%–94%).

Or

FDA regimen (EUA FDA, May 2020)

● Patients with severe disease requiring invasive mechanical ventilation

and/or ECMO
IV

○ Weight between 3.5 kg and <40 kg: Use Remdesivir (100 mg)
lyophilized powder only; 5 mg/kg OD, infused over 30–120
minutes on day 1, followed by 2.5 mg/kg OD, infused over
30–120 minutes OD for 9 days
○ Weight ≥40 kg: 200 mg OD, infused over 30–120 minutes on
day 1, followed by 100 mg OD, infused over 30–120 minutes for
9 days
○ Treatment should not be initiated in patients with serum ALT
level ≥5 times ULN at baseline
● Patients with severe disease not requiring invasive mechanical
ventilation and/or ECMO
IV

○ Weight between 3.5 kg and <40 kg: Use Remdesivir (100 mg)
lyophilized powder only; 5 mg/kg OD, infused over 30–120 min
on day 1, followed by 2.5 mg/kg OD, infused over 30–120
minutes OD for 4 days, extendable up to 5 additional days (i.e.
up to a total of 10 days) if no clinical improvement is seen

1 Updated: 05/05/2020
 ○ Weight ≥40 kg: 200 mg OD, infused over 30–120 minutes on
day 1 followed by 100 mg OD, infused over 30–120 minutes for
4 days; if a patient does not demonstrate clinical improvement,
treatment may be extended for up to 5 additional days (i.e. up
to a total of 10 days)
○ Treatment should not be initiated in patients with serum ALT
level ≥5 times ULN at baseline
NOTE Clinical criteria for severe disease, as per FDA, is SpO2 ≤94% on

ambient air, requiring supplemental oxygen, mechanical ventilation, or

EMCO.

Dosage Adjustments

Hepatic Impairment

● Use is not recommended unless the potential benefit outweighs the

risk
● Hepatic laboratory testing should be performed in all patients before
starting Remdesivir and daily while receiving Remdesivir.
Renal Impairment

● eGFR ≥30 mL/min: No dosage adjustment necessary

● eGFR <30 mL/min in adults and pediatric patients older than 7–28
days: Use is not recommended unless the potential benefit outweighs
the risk
● Serum creatinine level 1 mg/dL or greater in full-term neonates
between 7–28 days: Use is not recommended unless the potential
benefit outweighs the risk
Hypersensitivity reaction

● Consider a slower infusion time to prevent reaction; maximum of up to

120 minutes
Hepatotoxicity during therapy

● ALT level ≥5 times the ULN: Discontinue Remdesivir; may resume

when the ALT level is <5 times the ULN

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 ● ALT level elevation accompanied by signs or symptoms of liver
inflammation or increasing levels of conjugated bilirubin, alkaline
phosphatase, or INR: Discontinue Remdesivir

Pregnancy & Lactation

● Remdesivir should be used during pregnancy only if the potential

benefit justifies the potential risk for the mother and the fetus.
● Excretion in breast milk is unknown. Because of the potential for viral
transmission to SARS-CoV-2-negative infants and adverse reactions
from the drug, breastfeeding should be considered along with the
mother’s clinical need and any potential adverse effects on the
breastfed child.

Mode of Action

Remdesivir is an adenosine nucleotide prodrug that distributes into cells

where it is metabolized to form the pharmacologically active nucleoside

triphosphate metabolite. Metabolism of Remdesivir to remdesivir

triphosphate has been demonstrated in multiple cell types. Remdesivir

triphosphate acts as an analog of adenosine triphosphate (ATP) and

competes with the natural ATP substrate for incorporation into nascent RNA

chains by the SARS-CoV-2 RNA-dependent RNA polymerase, which results in

delayed chain termination during replication of the viral RNA. Remdesivir

triphosphate is a weak inhibitor of mammalian DNA and RNA polymerases

with low potential for mitochondrial toxicity.

Adverse Drug Reactions

Frequency not defined

● Gastrointestinal: Nausea and vomiting

● Hematologic: Prolonged prothrombin time
● Hepatic: Increased levels of serum ALT and/or AST
● Renal: ARF, decreased eGFR, and increased levels of serum creatinine

1 Updated: 05/05/2020
 ● Others: Infusion-related reaction (hypotension, nausea, and vomiting),
and fever

Contraindications & Warnings

Contraindicated in

● Patients with known hypersensitivity to any ingredient of Remdesivir

Increased risk for

● Serious and unexpected adverse events

● Infusion-related reactions
● Transaminase level elevations
Use with caution

● In patients with hepatic and renal impairment

● In patients above 65 years of age
● In pediatric patients and neonates
Special warning

Co-administration of Remdesivir and chloroquine phosphate or

hydroxychloroquine sulfate is not recommended as it may result in reduced

antiviral activity of Remdesivir. (FDA June 2020)

Monitoring Parameters

● Serum biochemistry, hematology, and levels of ALT, AST, bilirubin,

and ALP (should be performed daily)
● Monitor for potential adverse events
● Renal function tests (creatinine and creatinine clearance)

1 Updated: 05/05/2020
 Remdesivir

Remdesivir is an adenosine triphosphate analog first investigated as a potential drug for the
treatment of Ebola. It has shown activity against the coronavirus family, and the FDA has issued
an Emergency Use Authorization (EUA) to permit the emergency use of the unapproved product
Remdesivir for the treatment of suspected or laboratory-confirmed coronavirus disease 2019
(COVID-19) in severe hospitalized patients.

Adult dosing
Severe coronavirus disease 2019 (COVID-19) (EUA FDA)
IV
Patients with invasive mechanical ventilation and/or requiring extracorporeal membrane
oxygenation (ECMO)
● Loading dose: 200 mg OD, on day 1
● Maintenance dose:100 mg OD, for 9 days
Patients not requiring invasive mechanical ventilation and/or ECMO
● Loading dose: 200 mg OD, on day 1
● Maintenance dose: 100 mg OD, for 4 days. If a patient does not demonstrate clinical
improvement, treatment may be extended for up to 5 additional days (i.e. up to a total of
10 days).

Pediatric dose
Coronavirus disease 2019 (COVID-19) (EUA FDA)
IV
Bodyweight ≥40 kg, requiring invasive mechanical ventilation and/or ECMO
● Loading dose: 200 mg OD, infused over 30 to 120 min on day 1
● Maintenance dose: 100 mg OD, infused over 30 to 120 min for 9 days.
Bodyweight ≥40 kg, not requiring invasive mechanical ventilation and/or ECMO
● Loading dose: 200 mg OD, infused over 30 to 120 min on day 1

1 Updated: 05/05/2020
 ● Maintenance dose: 100 mg OD, infused over 30 to 120 min for 4 days. If a patient does
not demonstrate clinical improvement, treatment may be extended for up to 5 additional
days (i.e. up to a total of 10 days).
Bodyweight between 3.5 kg and <40 kg
● Loading dose: 5 mg/kg OD, infused over 30 to 120 min on day 1
● Maintenance dose: 2.5 mg/kg OD, infused over 30 to 120 min once daily for 9 days
(patients requiring invasive mechanical ventilation and/or ECMO) or for 4 days (patients
not requiring invasive mechanical ventilation and/or ECMO). If a patient does not
demonstrate clinical improvement, treatment may be extended for up to 5 additional days
(i.e. up to a total of 10 days).
● Use only Remdesivir for injection, 100 mg, lyophilized powder only.

Dose adjustment
Hepatic impairment
● Hepatic laboratory testing should be performed in all patients prior to starting Remdesivir
and daily while receiving Remdesivir. Treatment should not be initiated in patients with
ALT level ≥ 5 times the upper limit of the normal at baseline
● Remdesivir should be discontinued in patients who develop
○ ALT level ≥ 5 times the upper limit of the normal during treatment with
Remdesivir. Remdesivir may be restarted when the ALT level is < 5 times the
upper limit of normal.
○ ALT level elevation accompanied by signs or symptoms of liver inflammation or
increasing levels of conjugated bilirubin, alkaline phosphatase, or INR
Renal impairment
● Adult and pediatric patients (>28 days old) must have eGFR determined, and full-term
neonates (≥7 days to ≤28 days old) must have serum creatinine level determined before
dosing.
● Remdesivir is not recommended in adults and pediatric patients (>28 days old), with
eGFR less than 30 mL per minute or in full-term neonates (≥7 days and ≤28 days old)
with serum creatinine clearance ≥1 mg/dL, unless the potential benefit outweighs the
potential risk.

Pregnancy and lactation

● Remdesivir should be used during pregnancy only if the potential benefit justifies the
potential risk for the mother and the fetus.

1 Updated: 05/05/2020
 ● Excretion in breast milk is unknown, because of the potential for viral transmission to
SARS-CoV-2-negative infants and adverse reactions from the drug, breastfeeding should
be considered along with the mother’s clinical need and any potential adverse effects on
the breastfed child.

Mechanism of action
Remdesivir is a prodrug that metabolizes into an adenosine nucleotide analog (GS-441524),
which interferes with the action of viral RNA-dependent RNA polymerase and evades
proofreading by viral exoribonuclease (ExoN), causing a decrease in viral RNA production
including SARS CoV-2.
Drug interactions
● Co-administration of Remdesivir and chloroquine phosphate or hydroxychloroquine
sulfate reduces the antiviral activity of Remdesivir.

Adverse drug reactions

Frequency not defined
● Gastrointestinal: Nausea, vomiting
● Hematologic: Prolonged prothrombin time
● Hepatic: Increased serum alanine aminotransferase, increased aspartate aminotransferase

Contraindications and warnings

Contraindicated in
● Patients with known hypersensitivity to any ingredient of Remdesivir
Increased risk for
● Serious and unexpected adverse events
● Infusion-related reactions
● Transaminase level elevations
Use with caution
● In patients with hepatic and renal impairment
● In patients above 65 years of age
● In pediatric patients and neonates

1 Updated: 05/05/2020
 Monitoring parameters

● Serum chemistries, hematology, ALT, AST, bilirubin, and alkaline phosphatase ( should
be performed daily)
● Monitor for potential adverse events
● Renal function tests (creatinine and creatinine clearance).

General considerations
● Remdesivir should not be administered simultaneously with any other medication. The
compatibility of Remdesivir injection with IV solutions and medications other than saline
is not known.
● No preservative or bacteriostatic agent present Remdesivir formulation, aseptic technique
must be used in the preparation of the final parenteral solution. Administer immediately
after preparation and unused portion of a single-dose Remdesivir vial should be
discarded.

1 Updated: 05/05/2020