Coronavirus disease (COVID-19) is an infectious disease caused by the SARS-CoV-2 virus, which can spread from an infected person’s mouth or nose in small liquid particles when they cough, sneeze, speak, sing or breathe. These particles range from larger respiratory droplets to smaller aerosols. The viral material hangs out in these droplets and can be breathed into the respiratory tract (your windpipe and lungs), where the virus can then cause an infection. It’s possible that you could acquire SARS-CoV-2 if you touch your mouth, nose, or eyes after touching a surface or object that has the virus on it. Older people and those with underlying medical conditions like cardiovascular disease, diabetes, chronic respiratory disease, or cancer are more likely to develop serious illness. Remdesivir is the first antiviral drug which has been approved by the FDA for the treatment of COVID-19. It can be administered by adult and pediatric patients, who are around 12 years of age and older and weighing at least 40 kilograms (about 88 pounds).  Remdesivir is highly advantageous for critically ill patients requiring supplemental oxygen via high-flow nasal cannula or mask, or non-invasive mechanical ventilation, is uncertain. Remdesivir does not benefit and may harm critically ill patients already receiving mechanical ventilation or requiring extra-corporeal membrane oxygenation (ECMO). Importantly, most remdesivir studies were performed before corticosteroids, such as dexamethasone, were widely used to treat COVID-19 patients. Since corticosteroids are effective treatments when prescribed for COVID-19, it is unclear from the remdesivir trial data we reviewed whether remdesivir provides additional benefit.

Remdesivir is a nucleotide prodrug of an adenosine analog which binds to the viral RNA-dependent RNA polymerase, inhibiting viral replication by terminating RNA transcription. Remdesivir is available in two formulations for IV administration, a concentrated solution and a lyophilized powder. Remdesivir is reconstituted using sterile water and should be completely dissolved and clear prior to withdrawal from the vial. It must be further diluted in either 100 mL or 250 mL of normal saline solution using strict aseptic technique, as the product contains no preservative or bacteriostatic agent. Remdesivir has provided its best activity against SARS-CoV-2. Remdesivir should be started within 7 days of symptom onset and administered for 3 days. In vitro and preclinical in vivo animal models supported the effectiveness of remdesivir against SARS-CoV-2 and related coronaviruses. These include a recent in vitro study of remdesivir assessing antiviral activity against SARS-CoV-2.

Interaction with minor substrate of cytochrome P450 (CYP) 3A4 and a substrate of the drug transporters organic anion transporting polypeptide (OATP) 1B1 and P-glycoprotein has been observed with remdesivir administration. Additionally, mild elevation in transaminase levels has been observed among pregnant women. Remdesivir can cause gastrointestinal symptoms (e.g., nausea), elevated transaminase levels, an increase in prothrombin time without a change in the international normalized ratio, and hypersensitivity reactions. Remdesivir should be administered at a stage where severe hypersensitivity reactions, such as anaphylaxis, can be managed.  Any other drug interaction with chloroquine phosphate or hydroxychloroquine sulfate is possible. Thus, Coadministration of these drugs can decrease remdesivir's antiviral activity and should be avoided.

Conclusion:

Recovery from COVID-19 depends more on the host’s immune system than on antiviral therapy, and that sustained viral suppression due to remdesivir is insufficient to reverse the inflammatory cascade associated with progressed disease. Recovery from COVID-19 may depend on both the prompt use of antivirals and modulation of the host immune system.  Remdesivir speeds time to recovery by preventing worsening to clinical states that would extend the course of hospitalization and increase intensive respiratory support, thereby reducing the overall demand for hospital care.

Media Contact:

Denise Williams
Journal Manager
Systematic reviews in pharmacy
Email: submissions@sysrevpharma.org