Remivir

Remdesivir has an FDA Emergency Use Authorization for use in adults and children with suspected or confirmed COVID-19 in hospital with an SpO2 ≤94%.

Requiring Supplemental Oxygen

Mechanical Ventilation

Extracorporeal Membrane Oxgenation(ECMO)

Broad-spectrum antiviral medication

Remdesivir is a preparation of Remdesivir. It 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 act as an analogue 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 polymerase with low potential for mitochondrial toxicity.

Dosing: Adult

Note: Remdesivir is currently under investigation for use in the treatment of coronavirus disease 2019 (COVID-19) (see ClinicalTrials.gov). At this time, safety and efficacy have not been established. However, we provide preliminary dosing information based on clinical trials in process (Gilead 2020; NIH 2020a; NIH 2020b; NIH 2020c). Whenever possible, treatment should be given as part of a clinical trial. No specific drug-drug interaction data are available. Minimize any unnecessary comedication whenever possible given lack of information about interaction risk.

Coronavirus disease 2019 (COVID-19): IV: Limited data available; dosing used in clinical trials: 200 mg as a single dose on day 1, followed by 100 mg once daily for a total duration of 5 to 10 days (Gilead 2020; NIH 2020a; NIH 2020b; NIH 2020c).

The FDA Emergency Use Authorization suggests a loading dose of 200mg once daily in patients ≥ 40 kg or 5 mg/kg once daily in patients 3.5 kg to less than 40 kg, followed by a maintenance dose of 100mg once daily in patients ≥ 40 kg or 2.5 mg/kg once daily in patients 3.5 kg to less than 40 kg.13 Patients not needing invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) should be treated for 5 days (including the loading dose on day 1), up to 10 days if they do not show improvement.13 Patients requiring invasive mechanical ventilation or ECMO should be treated for 10 days.13

Clinical trials used a regimen of 200mg once daily on the first day, followed by 100mg once daily for another 9 days.6,9,10 Early data suggests that some patients may benefit from only 5 days of treatment.8

Dosing: Pediatric

Coronavirus disease 2019 (COVID-19), treatment: No data available; trials ongoing:

Note: Remdesivir is currently under investigation for use in the treatment of COVID-19 (see ClinicalTrials.gov). Pediatric patients with severe disease are being considered for compassionate use access. At this time, safety and efficacy have not been established in adult or pediatric patients; as data and experience in pediatric patients continue to evolve, dosing will be updated as appropriate. Whenever possible, treatment should be given as part of a clinical trial. No specific drug-drug interaction data are available. Minimize any unnecessary comedication whenever possible given lack of information about interaction risk.

Children and Adolescents ≤17 years: Dosing based on clinical experience and trials in pediatric patients treated for Ebola virus disease (WHO 2018); optimal dose has not been established for COVID-19. Optimal duration for treatment of COVID-19 not established; total duration of 5 to 10 days is being evaluated in clinical trials in adults with COVID-19 (NIH 2020a; NIH 2020b; NIH 2020c). In pediatric Ebola virus experience, doses were infused over 30 minutes (WHO 2018).

<40 kg: IV: 5 mg/kg/dose as a single dose on day 1, followed by 2.5 mg/kg/dose once daily.

≥40 kg: IV: 200 mg as a single dose on day 1, followed by 100 mg once daily.

Adolescents ≥18 years: IV: 200 mg as a single dose on day 1, followed by 100 mg once daily for a total duration of 5 to 10 days; dosing based on ongoing clinical trials for COVID-19 in adults (Gilead 2020; NIH 2020a; NIH 2020b; NIH 2020c).

Dosage Modifications:

Renal impairment:

Pharmacokinetics have not been evaluated in patients with renal impairment

Use in patients with renal impairment is based on potential risk and potential benefit considerations

eGFR ≥30 mL/min: No dose adjustment

eGFR <30 mL/min: Not recommended unless the potential benefit outweighs potential risk

Hepatic impairment:

Not evaluated; unknown if dosage adjustment required

Use only if potential benefit outweighs risk

Due to antagonism observed in cell culture, concomitant use of Remdesivir with chloroquine phosphate or hydroxychloroquine sulfate is not recommended and Microbiology Drug-drug interaction trials of VEKLURY and other concomitant medications have not been conducted in humans. Remdesivir and its metabolites are in vitro substrates and/or inhibitors of certain drug metabolizing enzymes and transporters. The clinical relevance of these in vitro assessments has not been established

Remdesivir is at least partially metabolized by the cytochrome P450 enzymes CYP2C8, CYP2D6, and CYP3A4.Blood plasma concentrations of remdesivir are expected to decrease if it is administered together with cytochrome P450 inducers such as rifampicin, carbamazepine, phenobarbital, phenytoin, primidone, and St John's wort.

The most common adverse effects in studies of remdesivir for COVID‑19 include respiratory failure and organ impairment, including low albumin, low potassium, low count of red blood cells, low count of platelets that help with clotting, and yellow discoloration of the skin. Other reported side effects include gastrointestinal distress, elevated transaminase levels in the blood (liver enzymes), and infusion site reactions.

Other possible side effects of remdesivir include:

Infusion‐related reactions. Infusion‐related reactions have been seen during a remdesivir infusion or around the time remdesivir was given.Signs and symptoms of infusion‐related reactions may include: low blood pressure, nausea, vomiting, sweating, and shivering.

Increases in levels of liver enzymes, seen in abnormal liver blood tests.Increases in levels of liver enzymes have been seen in people who have received remdesivir, which may be a sign of inflammation or damage to cells in the liver.

Remdesivir is under study for the treatment of coronavirus disease 2019 (COVID-19). Although pregnancy has been an exclusion during the initial clinical trials (NIH 2020a; NIH 2020b; NIH 2020c), this medication may be available for compassionate use in pregnant women.

The American College of Obstetricians and Gynecologists (ACOG) and the Society for Maternal-Fetal Medicine (SMFM) have developed an algorithm to aid practitioners in assessing and managing pregnant women with suspected or confirmed COVID-19 (https://www.acog.org/topics/covid-19; https://www.smfm.org/covid19). Interim guidance is also available from the CDC for pregnant women who are diagnosed with COVID-19 (https://www.cdc.gov/coronavirus/2019-ncov/hcp/inpatient-obstetric-healthcare-guidance.html).

Data collection to monitor maternal and infant outcomes following exposure to COVID-19 during pregnancy is ongoing. Health care providers are encouraged to enroll females exposed to COVID-19 during pregnancy in the Organization of Teratology Information Specialists (OTIS) pregnancy registry (877-311-8972; https://mothertobaby.org/join-study/) or the PRIORITY (Pregnancy CoRonavIrus Outcomes RegIsTrY) (415-754-3729, https://priority.ucsf.edu/).

There is no human experience of acute overdosage with VEKLURY. Treatment of overdose with VEKLURY should consist of general supportive measures including monitoring of vital signs and observation of the clinical status of the patient. There is no specific antidote for overdose with remdesivir.

Please do not reuse or save unused Remdesivir Lyophilized powder, injection solution or diluted solution for infusion for further use. This product contains no preservatives. Lyophilized Powder: Please store Remdesivir for injection, 100 mg, vials at temperature not exceeding 30°C in a dry place until required for use. Protect from light & moisture. Do not use after expiration date. After reconstitution: vials can be stored up to 4 hours at room temperature (20°C-25°C) prior to administration or 24 hours at refrigerated temperature (2°C-8°C). Please dilute within the same day as administration. Diluted Solution for Infusion: Please store diluted Remdesivir solution for infusion up to 4 hours at room temperature (20°C-25°C) or 24 hours at refrigerated temperature (2°C-8°C).

COVID-19 Only