An antiviral medication called Remdesivir (Veklury) has activity against SARS-CoV-2 (COVID-19). It has received FDA approval for the hospitalization-required COVID-19 therapy for adult and pediatric patients.

In conjunction with Baricitinib, Remdesivir has received emergency FDA approval for patients with severe COVID-19 infection who require ECMO, invasive mechanical ventilation, or supplemental oxygen (extracorporeal membrane oxygenation).

Uses of Remdesivir (Veklury):

• Only hospitals or other healthcare facilities equipped to provide acute inpatient hospital care should administer the medication.
• When treating COVID-19 infection in adults and children 12 years of age and older who need to be hospitalized and weigh at least 40 kg, it is advised.

Update November 19th, 2020:

"FDA Approved Baricitinib (Olumiant) in combination with Remdesivir for COVID-19 infection"

FDA on 19th November approved Remdesivir + Baricitinib for the treatment of patients infected with coronavirus fulfilling the following criteria [Ref]:

• Patients requiring extracorporeal membrane oxygenation (ECMO).
• Adult and pediatric patients who are 2 years of age or older
• Patients on invasive mechanical ventilation
• Those who require supplemental oxygen

Update - November 20th, 2020:

"WHO recommends against the use of Remdesivir in patients with COVID-19 infection!"

28 participants were clinical care professionals, 4 were patient companions, and 1 was an ethicist who collaborate internationally to create guidelines created the most recent recommendations telling doctors not to administer "Remdesivir" to patients who have COVID-19 infection.

Data from WHO Solidarity Trial and three randomized clinical trials that were evaluated did not support remdesivir usage in COVID-19 infected patients. The WHO recommendation states [Ref]:

The evidence suggested no important effect on mortality, need for mechanical ventilation, time to clinical improvement, and other patient-important outcomes.

Remdesivir (Veklury) Dose in Adults and children weighing 40 kgs or more:

Note:

• Before treatment initiation, perform renal and liver function testing and calculate the estimated GFR.
• Monitor prothrombin time prior to treatment initiation and during the treatment in all patients.

Remdesivir (Veklury) Dose for COVID-19 Infection Treatment:

• Loading Dose: On day 1, administer a single intravenous infusion of 200 milligrams as the loading dose.
• After a loading dosage on the first day, start your maintenance treatment with a daily intravenous infusion of 100 mg.
• Treatment Duration:
  • Patients needing ECMO or invasive mechanical ventilation
    • Ten days are the suggested length of the course of treatment.
  • Patients who do not need invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO):
    • The suggested duration is a total of five days.
    • The duration of treatment may be delayed to a total of 10 days in patients who do not show significant improvement within the five days of treatment.

Remdesivir (Veklury) Dose in Children:

The drug's safety and effectiveness for usage in patients twelve years of age or younger or weighing less than forty kg have not been established. Children 12 years of age and older who weigh at least 40 kg should refer to "Dose in Adults" for the recommended dosage.

Pregnancy Risk Category: C

• Clinical experiments are being carried out right now. The amount of data is modest. To evaluate for drug-related harmful maternal or fetal outcomes, the data found from published case files and compassionate use of Remdesivir in pregnancies are not adequate.
• Studies on animal reproduction did not reveal any adverse outcomes for fetal health at 4x the recommended doses.
• Patients who are pregnant and are admitted to a hospital are at greater risk for adverse pregnancy outcomes because of COVID-19 infection.

Remdesivir use during breastfeeding:

• It is unknown whether the drug can be excreted into breast milk. The drug was detected in breastmilk from lactating animals in animal studies.
• Manufacturers recommend weighing the benefits and risks of drug treatment for the mother against the benefits of breastfeeding.

Remdesivir Dose in Kidney Disease:

Remdesivir has not been studied for the treatment of patients with kidney dysfunction. The intravenous formulation contains betadex sulfobutyl ether sodium that is excreted via the kidneys. The manufacturer recommends avoiding it in patients with an estimated GFR of less than 30 ml/minute. Renal functions and eGFR should be calculated before treatment initiation and during the treatment.

It is not advised to use in individuals with eGFR that is lower than 30 ml/minute.

Remdesivir Dose in Liver disease:

The manufacturer recommends monitoring liver functions before treatment initiation and as clinically indicated during treatment. There are no dosage adjustments provided in the manufacturer's labeling.

Side effects of Remdesivir (Veklury):

• Hypersensitivity reactions:
  • Hypersensitivity reactions including serious anaphylactic reactions may occur.
  • Urticaria
  • Itching
  • Rash
  • Swelling around the face and eyes.
  • Difficulty breathing
• Hepatotoxicity:
  • Liver enzyme elevations predominantly ALT and AST may occur.
• Extravasation:
  • Administration site extravasation can occur resulting in vesication
• Neurological side effects:
  • Seizures

Contraindications to Remdesivir (Veklury):

Veklury is not recommended for patients suffering from hypersensitivity reactions to any component or drug.

Alerts and precautions

• Hypersensitivity reactions:
  • They may manifest as hypotension or shortness of breath, tachycardia or hypoxia, fever, and angioedema.
  • To avoid hypersensitivity reactions, it is best to give the drug by slow intravenous injection for at least two hours.
  • Hypersensitivity reactions, including infusion-related allergic reactions, may occur. Itching, nausea, urticaria, itching, and other allergic reactions can all occur. Anaphylactoid reactions can be serious and may lead to death.
  • Patients should be monitored closely during and after the administration of the drug.
  • Hypersensitivity reactions can be severe and should be stopped immediately.
  • Patients who have a history of hypersensitivity reactions to the drug should be advised not to take it.
• Hepatotoxicity:
  • It is not uncommon to experience mild or moderate elevations of liver enzymes (ALT, AST), but these usually disappear after discontinuing treatment.
  • Patients with COVID-19 infection may also experience mild to moderate transaminitis.
  • The treatment might need to be stopped if the ALT is higher than 10 times the normal upper limit.
  • As indicated, liver function should be checked at baseline and periodically throughout treatment.
  • Treatment withdrawal may be necessary for patients whose ALT levels are raised but not by more than 10 times the typical upper limit.
• Use Hydroxychloroquine or Chloroquine Phosphate in conjunction
  • Patients who take concomitant hydroxychloroquine and chloroquine may have lower antiviral activity.
  • Remdesivir is not recommended for use with hydroxychloroquine phosphate or chloroquine phosphate due to its antagonistic activity. Both antimalarial drugs block intracellular metabolic activation.

Monitoring Parameters:

• Observe for hypersensitivity reactions
• Monitor liver functions and renal functions at baseline and as clinically indicated during the treatment.
• Monitor the oxygenation status of the patient.

How to administer Remdesivir (Veklury)?

The medication is given slowly intravenously over the course of 30 to 120 minutes. It shouldn't be taken at the same time as any other drug. It is unknown whether the product will work with liquids other than 0.9 percent saline.

There are no preservatives or bacteriostatic agents in the product. While preparing the solution, caution should be exercised to prevent any unintentional contamination.

The prepared solution should be infused as soon as possible following preparation. Before creating the final solution, the injection needs to equilibrate at ambient temperature.

Vials that are sealed can be kept at room temperature for up to 12 hours without dilution. The injection needs to be diluted in a 250 ml infusion bag with 0.9 percent saline.

To mix the solution bag, invert the bag 20 times. Avoid shaking the bag. For 1 day at ambient temperature or 2 days at a refrigerator's temperature, the produced solution is stable.

Mechanism of action of Remdesivir (Veklury):

COVID-19 is susceptible to the antiviral medication Remdesivir (Veklury). It inhibits the crucial for viral replication SARS-CoV2 essential RNA polymerase.

After it has been distributed into cells, it is transformed to AMP intermediate and metabolised. It is converted to active form depending on the type of cell.

Cellular kinases that phosphorylate it to the pharmacologically active nucleoside triphosphate metabolism. RDV-TP (Remdesivir Triphosphate) is incorporated by the SARS-2 RNA-dependent RNA polymerase. It functions as an adenosine triphosphate analogue.

As a result, the viral RNA replication experiences a delayed chain termination.

Protein binding:

• 88 - 93%

Half-life elimination:

• One hour

Metabolism:

• CYP3A (10%)
• CES1 (80%)
• Cathepsin A (10%)

Drug elimination:

• Major pathway of drug removal: 80% of the medicine is metabolized, 10 % is secreted in urine, and 10% (Not detected)

International Brand Names of Remdesivir:

• Veklury (GiLead Sciences)

Remdesivir Brand Names in Pakistan:

Veklury (GiLeads Sciences)

Correct Spelling: Remdesivir Incorrect spellings: Remdesvir, Remedesvir, Ramdesvir, Rimdesvir, Remdesvir, Remdesevir, Remdesiver.