Although the US Food and Drug Administration (FDA) has granted emergency use authorization of remdesivir (Gilead Sciences, Inc., Foster City, California) to treat COVID-19, the disease caused by SARS-CoV-2, the drug is considered an investigational agent, not yet formally approved by the FDA and whose efficacy and safety has not yet been fully characterized. Remdesivir has been shown to be effective in reducing the time to recovery of people with COVID-19 disease. It has not been tested in a large controlled clinical trial of pregnant women with COVID-19; however, remdesivir has been given to pregnant women infected with COVID-19 in a compassionate use protocol. For pregnant women, the drug should only be used if the potential benefit justifies the potential risk to the mother and fetus.1
Pharmacology. Remdesivir is a nucleoside RNA polymerase inhibitor. It has a molecular formula of
C27H35N6O8P and a molecular weight of 602.6 g/mol.1
Mechanism of action. From FDA’s fact sheet: “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 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.”1
Remdesivir is authorized for treatment of hospitalized patients with severe COVID-19 disease, defined as patients with an oxygen saturation ≤ 94% on room air or requiring supplemental oxygen or requiring mechanical ventilation or requiring extracorporeal membrane oxygenation (ECMO). The optimal dose and duration of treatment of COVID-19 with remdesivir is unknown.1
Prior to initiating treatment, the estimated glomerular filtration rate should be documented to be ≥ 30 mL/min. An excipient used in the remdesivir formulation—sulfobutylether-β-cylcodextrin sodium salt—is renally cleared and accumulates in patients with decreased renal function.
Baseline liver function tests should be performed prior to treatment and daily during the course of treatment. Remdesivir should not be initiated in patients with an alanine aminotransferase (ALT) level ≥ 5 times the upper limit of normal at baseline. Remdesivir should be discontinued in patients who develop an ALT level ≥ 5 times the upper limit of normal or in patients who develop elevated ALT levels and have increased bilirubin, alkaline phosphatase, or international normalized ratio.1
In one open-label study (GS-US-540-5773), remdesivir treatment was discontinued due to an adverse event in 5% of patients on a 5-day regimen and in 10% of patients on a 10-day regimen.1
Under the emergency use authorization, two treatment protocols have been proposed depending on the clinical severity of the COVID-19 infection1:
- Protocol 1: For people with COVID-19 requiring mechanical ventilation and/or ECMO, the duration of therapy is 10 days, beginning with a loading dose of remdesivir 200 mg infused intravenously for 30 to 120 minutes on day 1 followed by a once-daily dose of 100 mg for 9 days.
- Protocol 2: For people with COVID-19 disease not requiring mechanical ventilation and/or ECMO, the duration of therapy is 5 days, beginning with a loading dose of remdesivir 200 mg infused intravenously for 30 to 120 minutes on day 1 followed by a once-daily dose of 100 mg for 4 days. If the patient does not show clinical improvement, treatment may be extended for an additional 5 days.
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