Monograph: |
REMDESIVIR, OR GS-5734, IS AN ADENOSINE TRIPHOSPHATE ANALOG FIRST DESCRIBED IN THE LITERATURE IN 2016 AS A POTENTIAL TREATMENT FOR EBOLA. IN 2017, ITS ACTIVITY AGAINST THE CORONAVIRUS FAMILY OF VIRUSES WAS ALSO DEMONSTRATED. REMDESIVIR IS ALSO BEING RESEARCHED AS A POTENTIAL TREATMENT TO SARS-COV-2, THE CORONAVIRUS RESPONSIBLE FOR COVID-19.
PHARMACOLOGY
INDICATION
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%.13 THIS IS NOT THE SAME AS AN FDA APPROVAL.12
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.,,10 EARLY DATA SUGGESTS THAT SOME PATIENTS MAY BENEFIT FROM ONLY 5 DAYS OF TREATMENT.
REMDESIVIR WAS ORIGINALLY INVESTIGATED AS A TREATMENT FOR EBOLA VIRUS, BUT HAS POTENTIAL TO TREAT A VARIETY OF RNA VIRUSES. ITS ACTIVITY AGAINST THE CORONAVIRUS (COV) FAMILY OF VIRUSES, SUCH AS SARS-COV AND MERS-COV, WAS DESCRIBED IN 2017, AND IT IS ALSO BEING INVESTIGATED AS A POTENTIAL TREATMENT FOR SARS-COV-2 INFECTIONS.,
ASSOCIATED CONDITIONS
Β· NOVEL CORONAVIRUS INFECTIOUS DISEASE (COVID-19)
PHARMACODYNAMICS
REMDESIVIR IS A NUCLEOSIDE ANALOG USED TO INHIBIT THE ACTION OF RNA POLYMERASE. THE DURATION OF ACTION IS MODERATE, AS IT IS GIVEN ONCE DAILY.13 PATIENTS SHOULD BE COUNSELLED REGARDING THE RISK OF INFUSION RELATED REACTIONS, ELEVATED TRANSAMINASES, AND POTENTIAL DECREASED EFFICACY WHEN COMBINED WITH HYDROXYCHLOROQUINE OR CHLOROQUINE .13
MECHANISM OF ACTION
REMDESIVIR IS A NUCLEOSIDE ANALOG THAT IS EXPECTED TO INHIBIT THE ACTION OF RNA POLYMERASE. BY INCORPORATING INTO RNA, ADDITIONAL NUCLEOTIDES CANNOT BE ADDED, TERMINATING RNA TRANSCRIPTION. VIRUSES WITH MUTATIONS IN RNA POLYMERASE TO DEVELOP PARTIAL RESISTANCE TO REMDESIVIR HAVE BEEN SHOWN TO BE LESS INFECTIVE.
ROUTE OF ELIMINATION
REMDESIVIR IS 74% ELIMINATED IN THE URINE AND 18% ELIMINATED IN THE FECES.13 49% OF THE RECOVERED DOSE IS IN THE FORM OF THE METABOLITE GS-441524 , AND 10% IS RECOVERED AS THE UNMETABOLIZED PARENT COMPOUND.13
HALF LIFE
A 10MG/KG INTRAVENOUS DOSE IN NON HUMAN PRIMATES HAS A PLASMA HALF LIFE OF 0.39H. THE NUCLEOSIDE TRIPHOSPHATE METABOLITE HAS A HALF LIFE OF 14H IN NON HUMAN PRIMATES. THE NUCLEOSIDE TRIPHOSPHATE METABOLITE HAS A HALF LIFE OF APPROXIMATELY 20 HOURS IN HUMANS.
CLEARANCE
DATA REGARDING THE CLEARANCE OF REMDESIVIR IS NOT READILY AVAILABLE.
TOXICITY
DATA REGARDING OVERDOSES OF REMDESIVIR ARE NOT READILY AVAILABLE.13 OVERDOSES OF OTHER NUCLEOSIDE ANALOGS LIKE ACYCLOVIR CAN BE MANAGED WITH SYMPTOMATIC AND SUPPORTIVE TREATMENT.
CHLOROQUINE THE THERAPEUTIC EFFICACY OF REMDESIVIR CAN BE DECREASED WHEN USED IN COMBINATION WITH CHLOROQUINE.
HYDROXYCHLOROQUINE THE THERAPEUTIC EFFICACY OF REMDESIVIR CAN BE DECREASED WHEN USED IN COMBINATION WITH HYDROXYCHLOROQUINE.
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