remdesivir

Remdesivir is an antiviral medication used to treat coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has led to the global pandemic that started in 2019. Remdesivir was developed after the outbreak of COVID-19 and was granted Emergency Use Authorization (EUA) in May 2020. Remdesivir was the first drug to receive FDA approval for the treatment of COVID-19, in October, 2020.

SARS-CoV-2 is an RNA virus that spreads through droplets when an infected person talks, coughs, sneezes or laughs. Remdesivir works by inhibiting SARS-CoV-2 RNA-dependent RNA polymerase, the enzyme that is essential for viral replication. Remdesivir is a prodrug that is metabolized in the body into its active form remdesivir triphosphate (RDV-TP). RDV-TP gets incorporated into the growing viral RNA chain and inhibits its synthesis and replication.

• Do not use in patients who are hypersensitive to remdesivir or any of its components
• Hypersensitivity reactions, including infusion-related and anaphylactic reactions have been observed, mostly within an hour of administration; slower infusion rate (up to 120 minutes) may reduce the risk of these reactions; in case of clinically significant reactions, discontinue remdesivir immediately and implement appropriate treatment
• Elevation of liver enzymes (transaminases) can occur; perform liver tests in all patients before starting therapy; consider discontinuing if ALT levels are higher than 10 times the upper normal limit, and discontinue if ALT elevation is accompanied by signs and symptoms of liver inflammation
• Do not co-administer with chloroquine or hydroxychloroquine; may reduce remdesivir’s antiviral activity

Common side effects of remdesivir include:

• Decrease in estimated glomerular filtration rate (eGFR)
• Decrease in creatinine clearance
• Increase in creatinine levels
• Decrease in hemoglobin levels
• Increase in blood glucose levels
• Decrease in lymphocytes
• Increase in blood clotting time (prothrombin time)
• Increase in serum levels of liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST)
• Nausea

Less common side effects of remdesivir include:

• Increase in bilirubin levels
• Generalized seizure
• Skin rash

Rare side effects of remdesivir include:

• Hypersensitivity reactions which may include
  • Low blood pressure (hypotension)
  • High blood pressure (hypertension)
  • Rapid heart rate (tachycardia)
  • Slow heart rate (bradycardia)
  • Low oxygen in tissues (hypoxia)
  • Fever
  • Shortness of breath (dyspnea)
  • Wheezing
  • Swelling of tissue under the skin and mucous membranes (angioedema)
  • Excessive sweating (diaphoresis)
  • Shivering
  • Severe allergic reaction (anaphylaxis)
• Increase in serum alkaline phosphatase
• Redness (erythema) at the injection site
• Leakage of drug from the vein (extravasation)
• Infusion related reactions
• Severe bradycardia
• Heart failure
• Acute liver failure

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug.

Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

Injection, Lyophilized Powder for Reconstitution

• 100mg/vial
• Note: Use lyophilized powder to prepare dose for children younger than 12 years or weight under 40 kg according to EUA for this group

Injection, Concentrated Solution

• 100mg/20mL (5mg/mL)

Adults and pediatric patients 12 years or older

Coronavirus Disease 2019 (COVID-19)

Indicated for treatment of COVID-19 in adults and pediatric patients 12 years or older who weigh 40 kg or more with positive results of direct severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral testing, requiring hospitalization, or are not hospitalized and have mild-to-moderate COVID-19 and are at high risk for progression to severe COVID-19, including hospitalization or death

Inpatient treatment

• Day 1 loading dose: 200 mg intravenous (IV) infused over 30-120 minutes, THEN
• Day 2 and thereafter: 100 mg IV every day
• Treatment duration
  • Not requiring invasive mechanical ventilation and/or extracorporeal membrane oxygenation (ECMO): 5 days; if clinical improvement not demonstrated, treatment may be extended up to 10 days in total
  • Requires invasive mechanical ventilation and/or ECMO: 10 days

Outpatient treatment

• Initiate as soon as possible after diagnosis of symptomatic COVID-19 has been made and within 7 days of symptom onset
• 200 mg IV on Day 1, then 100 mg IV on Days 2-3 (i.e. 3 consecutive days)

Dosage Modifications

Renal impairment

• Pharmacokinetics have not been evaluated in patients with renal impairment
• eGFR 30 mL/min or more: No dose adjustment
• eGFR below 30 mL/min: Not recommended; sulfobutylether-beta-cyclodextrin sodium salt (SBECD) excipient in the concentrated solution is renally cleared and accumulates in patients with decreased renal function

Hepatic impairment

• Not evaluated; unknown if dosage adjustment required

Dosing Considerations

Laboratory tests

• Obtain before initiating in all patients and while receiving as clinically appropriate
• Determine eGFR
• Perform hepatic laboratory testing
• Determine prothrombin time

Children younger than 12 years

COVID-19 in Younger Children (EUA) 

Emergency Use Authorization (EUA) issued for treatment of COVID-19 in pediatric patients weighing 3.5 kg to under 40 kg or children aged younger than 12 years who weigh at least 40 kg, with positive results of direct SARS-CoV-2 viral testing, who are hospitalized, or not hospitalized and have mild-to-moderate COVID-19 and are at high risk for progression to severe COVID-19, including hospitalization or death

Inpatient treatment

• Weight 3.5-40 kg
  • Day 1 loading dose: 5 mg/kg mg IV infused over 30-120 minutes, THEN
  • Day 2 and thereafter: 2.5 mg/kg IV every day
• Age younger than 12 years and weight 40 kg or more
  • Day 1 loading dose: 200 mg IV infused over 30-120 min, THEN
  • Day 2 and thereafter: 100 mg IV every day
• Inpatient treatment duration
  • Not requiring invasive mechanical ventilation and/or ECMO: 5 days; if clinical improvement not demonstrated, treatment may be extended up to 10 days in total
  • Requires invasive mechanical ventilation and/or ECMO: 10 days

Outpatient treatment

• Initiate as soon as possible after diagnosis of symptomatic COVID-19 has been made and within 7 days of symptom onset
• Weight 3.5-40 kg: 5 mg/kg IV on Day 1, then 2.5 mg/kg IV on Days 2-3
• Weight 40 kg or more: 200 mg IV on Day 1, then 100 mg IV on Days 2-3
• Administer for 3 consecutive days

Dosage Modifications

Renal impairment

• eGFR 30 mL/min or more: No dose adjustment
• Pediatric patients (older than 28 days) with eGFR below 30 mL/min: Not recommended
• Full-term neonates (7 days to 28 days) with serum creatinine more than 1 mg/dL: Not recommended
• Sulfobutylether-beta-cyclodextrin sodium salt (SBECD) excipient in the concentrated solution is renally cleared and accumulates in patients with decreased renal function

Hepatic impairment

• Not evaluated; unknown if dosage adjustment required

Dosing Considerations

• Administer only in a hospital or healthcare setting capable of providing acute care comparable to inpatient hospital care
• Use lyophilized powder to prepare dose for children younger than 12 years or weight below 40 kg according to EUA for this group

Laboratory tests

• Obtain before initiating in all patients and while receiving as clinically appropriate
• Determine eGFR for patients older than 28 days
• Measure serum creatinine for all full-term neonates aged 7-28 days
• Perform hepatic laboratory testing
• Determine prothrombin time

• There are no data on overdosage with remdesivir and there is no specific antidote for overdose.
• Overdose should be treated with general supportive measures including monitoring of vital signs and observation of the clinical status of the patient.

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

• Remdesivir has no known severe interactions with other drugs.
• Serious interactions of remdesivir include:
  • Chloroquine phosphate
  • hydroxychloroquine sulfate
• Moderate interactions of remdesivir include:
  • warfarin
• Remdesivir has no known mild interactions with other drugs.

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider of all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or health care provider if you have any questions about the medication.

• Remdesivir treatment should not be withheld if needed during pregnancy.
• Available data on use of remdesivir in pregnant women are insufficient to evaluate drug-related risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes, however, animal reproductive studies did not show any fetal harm.
• Untreated COVID-19 in pregnancy is associated with maternal and fetal risks, including preeclampsia, eclampsia, preterm birth, premature rupture of membranes, venous thromboembolic disease, and fetal death.
• Information on COVID-19 treatment during pregnancy continues to emerge; refer to current guidelines for the treatment of pregnant patients.
• The American College of Obstetricians and Gynecologists (ACOG) and the Society for Maternal-Fetal Medicine (SMFM) have developed an algorithm to help practitioners assess and manage pregnant patients with COVID-19 (https://www.acog.org/covid-19; https://www.smfm.org/covid19). Interim guidance is also available from the CDC at (https://www.cdc.gov/coronavirus/2019-ncov/hcp/inpatient-obstetric-healthcare-guidance.html).
• Data collection to monitor maternal and infant outcomes following exposure to remdesivir during pregnancy is ongoing.
  • Pregnant and recently pregnant patients exposed to remdesivir are encouraged to enroll in the registry (800-616-3791 or http://covidpr.pregistry.com).
  • Health care providers are encouraged to enroll patients exposed to COVID-19 during pregnancy in the Organization of Teratology Information Specialists (OTIS) pregnancy registry (877-311-8972; https://mothertobaby.org/join-study/).
• Remdesivir and its metabolite have been detected in breast milk in concentration considered acceptable for breastfeeding. There is, however, insufficient information and decision should be based benefits to the mother and potential risks to the infant. Viral particles have not been found in breast milk, however, the breastfeeding mother should take all precautions to avoid spreading the virus to the infant.

• Inform your healthcare provider:
  • If you have liver or kidney problems
  • If you are pregnant/breastfeeding or planning to
  • If you are taking chloroquine phosphate or hydroxychloroquine sulfate