Remdesivir


Concise Prescribing Info
Indications/Uses
Coronavirus disease 2019 (COVID-19).

It should be noted that:

- Remdesivir for the treatment of COVID-19 have not been definitely established, some data are available from several initial trials in the US and other countries.
- Remdesivir may be available for use in some countries under special agreement with manufacturer. Please refer to local regulatory agencies for relevant information. The safety and efficacy of remdesivir for the treatment of COVID-19 continue to be evaluated, and preliminary clinical trial results have shown that on average, patients treated with remdesivir had more rapid time to recovery.

- There is still lack of evidence to support the use of remdesivir empirically prior to confirmation of COVID-19, mild to moderate cases of COVID-19, pre- and post-exposure prophylaxis outside of clinical trial setting. On-going clinical trials hope to shed some light in these areas soon.

For healthcare professionals:

- Read the most up-to-date fact sheet when prescribing remdesivir.

- No specific drug-drug interaction data are available. Minimise any unnecessary co-medication whenever possible given lack of information about interaction risk.

- To alleviate the risks of this unapproved drug during pandemic use, local regulatory agencies may require healthcare facilities and healthcare providers to comply with certain regulations for administration of remdesivir. Please refer to respective local regulatory agencies for further information.
Dosage/Direction for Use
Adult : IV In hospitalised patients with severe case: 200 mg as a single dose on day 1, then 100 mg once daily starting on day 2. Duration: Patients not requiring mechanical ventilation/ECMO: 5 days; may extend for up to 5 additional days (total of 10 days) in patients who do not demonstrate clinical improvement. Patients requiring invasive mechanical ventilation/ECMO: 10 days.
Dosage Details
Intravenous
Coronavirus disease 2019 (COVID-19)
Adult: In hospitalised patients with severe case: 200 mg as a single dose on day 1, followed by 100 mg once daily starting on day 2. Treatment duration: Patients not requiring mechanical ventilation/extracorporeal membrane oxygenation (ECMO): 5 days; may extend for up to 5 additional days (total of 10 days) in patients who do not demonstrate clinical improvement. Patients requiring invasive mechanical ventilation/ECMO: 10 days. Doses are given via infusion over 30-120 minutes. Dosage recommendation is based on currently available data from clinical studies and may vary among local guidelines or countries.
Child: In hospitalised patients with severe disease (for compassionate use): As lyophilised powder: 3.5-<40 kg: 5 mg/kg on day 1, followed by 2.5 mg/kg once daily starting on day 2; ≥40 kg: As concentrated solution or lyophilised powder: Same as adult dose. Treatment duration: Patients not requiring mechanical ventilation/ECMO: 5 days; may extend for up to 5 additional days (total of 10 days) in patients who do not demonstrate clinical improvement. Patients requiring invasive mechanical ventilation/ECMO: 10 days. Doses are given via infusion over 30-120 minutes. Dosage recommendations may vary among countries based on currently available data. Dosage recommendation is based on currently available data from clinical studies and may vary among local guidelines or countries.
Renal Impairment
eGFR <30 mL/min and patients receiving renal replacement therapies (e.g. haemodialysis, peritoneal dialysis, CRRT): Contraindicated.
Reconstitution
Lyophilised powder: Reconstitute with 19 mL of sterile water for injection and further dilute in NaCl 0.9% infusion bag prior to administration. Concentrated solution: Dilute in NaCl 0.9% infusion bag prior to administration. Administer immediately after preparation when possible.
Incompatibility
Do not administer simultaneously with any other IV drugs.
Contraindications
Hypersensitivity. Baseline ALT ≥5 times the upper limit of normal (ULN). Severe renal impairment (eGFR <30 mL/min) including patients receiving renal replacement therapies (e.g. haemodialysis, peritoneal dialysis, CRRT).
Special Precautions
Not recommended for the treatment of mild or moderate COVID-19 outside of a clinical trial. Renal and hepatic impairment. Children. Pregnancy and lactation; use only if potential benefits justify potential risks as there is limited data regarding the use of remdesivir in pregnant and lactating women.
Adverse Reactions
Significant: Increased transaminase levels; infusion-related and anaphylactic reactions, including angioedema, diaphoresis, dyspnoea, bradycardia or tachycardia, hypotension, nausea, rash, shivering, vomiting, wheezing.
Blood and lymphatic system disorders: Anaemia.
General disorders and administration site conditions: Pyrexia.
Investigations: Increased blood glucose, decreased Hb.
Metabolism and nutrition disorders: Hyperglycaemia.
Nervous system disorders: Headache.
Renal and urinary disorders: Increased serum creatinine, decreased eGFR or CrCl, acute kidney injury.
MonitoringParameters
Perform LFT, and haematology test at baseline and daily during therapy. Determine eGFR (in adult and children >28 days old) and serum creatinine (in full-term neonates 7-28 days old) prior to initiation and daily during therapy.
Drug Interactions
Diminished therapeutic effect with chloroquine or hydroxychloroquine.
Action
Description: Remdesivir is an adenosine nucleotide prodrug that is metabolised intracellularly to the pharmacologically active nucleoside triphosphate metabolite (GS-443902). Remdesivir triphosphate acts as an ATP analog and competes for incorporation into RNA chains by the RNA-dependent RNA polymerase, resulting in delayed chain termination during replication of the viral RNA. It has a broad spectrum of activity against members of CoVs (e.g. SARS-CoV, MERS-CoV), the filoviruses (e.g. EBOV, MARV), and paramyxoviruses (e.g. respiratory syncytial virus [RSV], Nipah virus [NiV], and Hendra virus) in studies.
Pharmacokinetics:
Absorption: Time to peak plasma concentration: 1.5-2 hours.
Distribution: Distributed to plasma and cellular components of blood. Plasma protein binding: Approx 88% (remdesivir); 2% (GS-441524).
Metabolism: Extensively metabolised intracellularly to the pharmacologically active nucleoside analog triphosphate GS-443902. Undergoes hydrolysis by esterases forming the intermediate metabolite, GS-704277. Phosphoramidate cleavage followed by phosphorylation forms the active triphosphate, GS-443902 while dephosphorylation of all phosphorylated metabolites results in the formation of nucleoside metabolite GS-441524.
Excretion: Mainly via urine (74%; 49% as the GS-441524 metabolite, 10% as unchanged drug); faeces (18%).
Chemical Structure

Chemical Structure Image
Remdesivir

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 121304016, Remdesivir. https://pubchem.ncbi.nlm.nih.gov/compound/Remdesivir. Accessed Aug. 17, 2020.

Storage
Lyophilised powder: Store below 30°C. Reconstituted solution: Store between 20-25°C (stable for up to 4 hours) or between 2-8°C (stable for up to 24 hours). Concentrated solution: Store between 2-8°C. Prior to dilution, equilibrate to 20-25°C (stable for up to 12 hours). Diluted solution for infusion: Store between 20-25°C (stable for up to 4 hours) or between 2-8°C (stable for up to 24 hours).
MIMS Class
References
Beigel JH, Tomashek KM, Dodd, LE et al. Remdesivir for the Treatment of Covid-19 - Preliminary Report. The New England Journal of Medicine. 2020 May. doi: 10.1056/NEJMoa2007764. Accessed 30/07/2020

Anon. Remdesivir. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 07/07/2020 .

Anon. Remdesivir. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 07/07/2020 .

Buckingham R (ed). Remdesivir. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 07/07/2020 .

Fact Sheet for Healthcare Providers Emergency Use Authorization (EUA) of Remdesivir (GS-5734). U.S. FDA. https://www.fda.gov/. Accessed 07/07/2020 .

Remdesivir by Gilead Sciences: FDA Warns of Newly Discovered Potential Drug Interaction That May Reduce Effectiveness of Treatment. U.S. FDA. https://www.fda.gov/. Accessed 07/07/2020 .

Should Remdesivir be used for COVID-19?. Ministry of Health - Singapore. https://www.moh.gov.sg/. Accessed 29/07/2020 .

Summary on Compassionate Use - Remdesivir Gilead. European Medicines Agency [online]. Accessed 07/07/2020 .

Veklury 100 mg Concentrate for Solution for Infusion (Gilead Sciences Ireland UC). European Medicines Agency [online]. Accessed 07/07/2020 .

Disclaimer: This information is independently developed by MIMS based on Remdesivir from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2020 MIMS. All rights reserved. Powered by MIMS.com
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