Remdesvir
Remdesivir is a type of broad-spectrum antiviral medication called a nucleotide analog. It is currently an investigational drug and not approved in any country for any use. Remdesivir is not FDA-approved. The majority of clinical decisions are made based on the historical epidemics Ebola, SARS, and MERS. Remdesivir is an inhibitor of the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp), which is essential for viral replication. Remdesivir is an adenosine nucleotide prodrug that distributes into cells where it is metabolized to form the pharmacologically active nucleoside triphosphate metabolite.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 delayed 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. Remdesivir is an antiviral medication developed for the treatment of certain viral infections, including the Ebola virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19. It belongs to a class of drugs known as nucleotide analogs.-Remdesivir is indicated for the treatment of COVID-19 in adults and pediatric patients (12 years of age and older, weighing at least 40 kg) requiring hospitalization. It is specifically recommended for use in cases with severe disease, including those requiring supplemental oxygen, mechanical ventilation, or extracorporeal membrane oxygenation (ECMO). -For treatment of suspected or laboratory confirmed corona virus disease 2019 (COVID- 19) in adults and children hospitalized with moderate to severe disease.
Lyophilized Powder Remdesivir for injection, 100 mg: Each single-dose vial of remdesivir for injection,100 mg, contains a sterile, preservative-free White to off-white to yellow lyophilized powder or lumps or solid that is to be reconstituted with 19 mL of Sterile Water for Injection and diluted into 0.9% saline prior to administration by intravenous infusion. Following reconstitution, each vial contains 5 mg/mL remdesivir reconcentrated solution with sufficient volume to allow withdrawal of 20 mL of 5 mg/mL solution containing 100 mg of remdesivir. Adult Patients • The dose of the drug for adults should be a single dose of 200 mg infused intravenously over 30-120 minutes on day 1 followed by a once-daily maintenance dose of 100 mg, infused intravenously over 30-120 minutes for 4 days. • Remdesivir is to be administered via intravenous infusion in a total volume of up to 250 mL 0.9% saline over 30 to 120 minutes • Extension of administration of the drug beyond 5 days to 10 days is not recommended. All adult patients must have creatinine clearance determined before dosing. Hepatic laboratory testing should be performed in all patients starting remdesivir and daily while receiving remdesivir dosing Pediatric Patients Dosing in pediatric patients is based upon physiologically based (PBPK) modeling and simulation of pharmacokinetic data from healthy adult subjects. The recommended pediatric dose for pediatric patients weighing between 3.5 kg and <40 kg should be calculated using the mg/kg dose according to the patient’s weight. The dose of the drug for pediatric patients weighing more than 40 kg should be a single dose of 200 mg infused intravenously over 30-120 minutes on day 1 followed by a once-daily maintenance dose of 100 mg, infused intravenously over 30-120 minutes for 4 days. • The dose for pediatric patients with bodyweight between 3.5 kg and less than 40 kg should be a single dose of 5 mg/kg infused intravenously over 30-120 minutes on day 1 followed by a once-daily maintenance dose of 2.5 mg/kg, infused intravenously over 30-120 minutes for 4 days. • Extension of administration of the drug beyond 5 days to 10 days is not recommended. Pediatric patients (>28 days old) must have an eGFR determined and full-term neonates (7 days to 28 days old) must have serum creatinine determined before dosing Hepatic laboratory testing should be performed in all patients before starting remdesivir and daily while receiving remdesivir dosing. -The recommended dose for adults and pediatric patients weighing at least 40 kg is a single loading dose of 200 mg on Day 1, followed by once-daily maintenance doses of 100 mg from Day 2 onwards. The duration of treatment may vary based on the severity of the illness.
-Significant hypersensitivity reactions to remdesivir or any components of the product. -Remdesivir is contraindicated in patients with a known hypersensitivity to the drug. Additionally, it should not be co-administered with strong inducers of CYP3A4 as it may reduce the plasma concentrations of remdesivir, potentially affecting its efficacy.
Paediatric: The safety and effectiveness of remdesivir for treatment of COVID-19 have not been assessed in pediatric patients. Monitor Renal function in paediatric patients. Pregnancy: Remdesivir should be used during pregnancy only if the potential benefit justifies the potential risk for the mother and the fetus. Lactation: There is no information regarding the presence of remdesivir in human milk, the effects on the breastfed infant, or the effects on milk production. Elderly: No overall differences in safety or effectiveness have been observed between elderly and other adult patients. -Healthcare providers should monitor renal and hepatic function in patients receiving remdesivir. It should be used with caution in patients with impaired renal function, and dosage adjustments may be necessary.
-Infusion-Related Reactions Infusion-related reactions have been observed during, and/or been temporally associated with, administration of remdesivir. Signs and symptoms may include hypotension, nausea, vomiting, diaphoresis, and shivering. If signs and symptoms of a clinically significant infusion reaction occur, immediately discontinue administration of remdesivir and initiate appropriate treatment. Increased Risk of Transaminase Elevations Transaminase elevations have been observed in healthy volunteers who received 200 mg of remdesivir followed by 100 mg doses for up to 10 days; the transaminase elevations were mild (Grade 1) to moderate (Grade 2) in severity and resolved upon discontinuation of remdesivir. Transaminase elevations have also been reported in patients with COVID-19 who received remdesivir -Common side effects of remdesivir may include nausea, increased levels of liver enzymes, and infusion-related reactions. Serious adverse events, such as acute respiratory failure, hypotension, and complications related to underlying diseases, have been reported.
-Remdesivir is primarily metabolized by the liver, and drug interactions may occur with drugs that are strong inducers or inhibitors of CYP3A4. Co-administration with these drugs should be approached with caution, and dosage adjustments may be necessary. -Chloroquine phosphate or hydroxychloroquine sulfate
