Remdesivir is approved by the Food and Drug Administration (FDA) for the treatment of COVID-19 in hospitalised adult and paediatric patients (aged ≥12 years and weighing ≥40 kg). It is also available through an FDA Emergency Use Authorization (EUA) for the treatment of COVID-19 in hospitalised paediatric patients weighing 3.5 kg to <40 kg or aged <12 years and weighing ≥3.5 kg. Remdesivir should be administered in a hospital or a healthcare setting that can provide a similar level of care to an inpatient hospital.
Hypothesis for the Use of Remdesivir
Remdesivir was associated with improved time to recovery in patients who required oxygen supplementation but not high-flow oxygen, non-invasive ventilation, or mechanical ventilation. Based on the results from various studies, the Panel recommends Remdesivir (without dexamethasone) as a treatment option for certain patients who require supplemental oxygen (e.g., those who require minimal supplemental oxygen).
Hypothesis for the Use of Remdesivir Plus Dexamethasone
The safety and efficacy of using Remdesivir plus dexamethasone for the treatment of COVID-19 have not been rigorously evaluated in clinical trials. Patients with severe COVID-19 may develop a systemic inflammatory response that leads to multiple organ dysfunction syndrome. The potent anti-inflammatory effects of corticosteroids might prevent or mitigate these hyper inflammatory effects. Thus, the combination of an antiviral agent, such as Remdesivir, with an anti-inflammatory agent, such as dexamethasone, may treat the viral infection and dampen the potentially injurious inflammatory response that is a consequence of the infection.
Patients Who Are Hospitalised With Moderate COVID-19 but Who Do Not Require Supplemental Oxygen
Recommendations
- The Panel recommends against the use of dexamethasone or other corticosteroids. Patients who are receiving dexamethasone or another corticosteroid for other indications should continue therapy for their underlying conditions as directed by their health care provider.
- There are insufficient data to recommend either for or against the routine use of Remdesivir in these patients. The use of Remdesivir may be appropriate in patients who have a high risk of disease progression.
For Hospitalised Patients With COVID-19 Who Require Supplemental Oxygen but Who Do Not Require Oxygen Delivery Through a High-Flow Device, Non-invasive Ventilation, Invasive Mechanical Ventilation, or Extracorporeal Membrane Oxygenation
Recommendations
The Panel recommends one of the following options for these patients:
- Remdesivir (e.g., for patients who require minimal supplemental oxygen)
- Dexamethasone plus Remdesivir (e.g., for patients who require increasing amounts of oxygen) or
- Dexamethasone (e.g., when combination therapy with Remdesivir cannot be used or is not available).
For Hospitalised Patients With COVID-19 Who Require Delivery of Oxygen Through a High-Flow Device or Non-invasive Ventilation but Not Invasive Mechanical Ventilation or Extracorporeal Membrane Oxygenation
Recommendations
- The Panel recommends one of the following options for these patients:
- Dexamethasone alone or
- A combination of dexamethasone plus Remdesivir.
- For patients who were recently hospitalised and who have rapidly increasing oxygen needs and systemic inflammation, add tocilizumab to one of the two options above.
For Hospitalised Patients With COVID-19 Who Require Invasive Mechanical Ventilation or Extracorporeal Membrane Oxygenation
Recommendations
- The Panel recommends the use of dexamethasone in hospitalised patients with COVID-19 who require invasive mechanical ventilation or ECMO.
Monitoring and Adverse Effects
Remdesivir can cause gastrointestinal symptoms (e.g., nausea), elevated transaminase levels, an increase in prothrombin time (without a change in the international normalised ratio), and hypersensitivity reactions.
Liver function tests and prothrombin time should be obtained in all patients before remdesivir is administered and during treatment as clinically indicated. Remdesivir may need to be discontinued if alanine transaminase (ALT) levels increase to >10 times the upper limit of normal and should be discontinued if an increase in ALT level and signs or symptoms of liver inflammation are observed
Considerations in Patients With Renal Insufficiency
Each 100 mg vial of remdesivir lyophilised powder contains 3 g of sulfobutylether beta-cyclodextrin sodium (SBECD), whereas each 100 mg/20 mL vial of remdesivir solution contains 6 g of SBECD.3 SBECD is a vehicle that is primarily eliminated through the kidneys. A patient with COVID-19 who receives a loading dose of remdesivir 200 mg would receive 6 g to 12 g of SBECD, depending on the formulation. This amount of SBECD is within the safety threshold for patients with normal renal function.4 Accumulation of SBECD in patients with renal impairment may result in liver and renal toxicities. Clinicians may consider preferentially using the lyophilised powder formulation (which contains less SBECD) in patients with renal impairment.
Because both remdesivir formulations contain SBECD, patients with an estimated glomerular filtration rate (eGFR) of <50 mL/min were excluded from some clinical trials of remdesivir; other trials had an eGFR cutoff of <30 mL/min. Remdesivir is not recommended for patients with an eGFR <30 mL/min due to lack of data.5 Renal function should be monitored before and during remdesivir treatment as clinically indicated.
Considerations in Pregnancy
- Pregnant patients were excluded from the clinical trials that evaluated the safety and efficacy of remdesivir for the treatment of COVID-19, but preliminary reports of remdesivir use in pregnant patients from the remdesivir compassionate use program are reassuring.
- Among 86 pregnant and postpartum hospitalised patients with severe COVID-19 who received compassionate use remdesivir, the therapy was well tolerated, with a low rate of serious adverse events.8
- Remdesivir should not be withheld from pregnant patients if it is otherwise indicated.
Considerations in Children
- The safety and effectiveness of using remdesivir to treat COVID-19 have not been evaluated in paediatric patients aged <12 years or weighing <40 kg.
- Remdesivir is available through an FDA EUA for the treatment of COVID-19 in hospitalised paediatric patients weighing 3.5 kg to <40 kg or aged <12 years and weighing ≥3.5 kg.
- A clinical trial is currently evaluating the pharmacokinetics of remdesivir in children (ClinicalTrials.gov Identifier NCT04431453).
References:
https://www.covid19treatmentguidelines.nih.gov/therapeutic-management/
https://www.covid19treatmentguidelines.nih.gov/antiviral-therapy/remdesivir/
https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting-sick/prevention.html