FDA approves use of antiviral drug remdesivir as an outpatient therapy for people with covid-19

Washington Post ^

[Blue Turtle]

Federal regulators Friday approved the use of the antiviral drug remdesivir for covid-19 outpatients at high risk of being hospitalized, providing a new treatment option for doctors struggling with shortages of effective drugs to counter the coronavirus.

[PA Presbyterian]

It’s also Bill Gates favorite poison. It was developed by Gilead and Gates has a major financial stake in Gilead. He and Fauci also backed it against Ebola. It was responsible for many deaths and the trial use of it had to be stopped. Fauci and Gates have been partners for twenty years. Bobby Kennedy’s book, The Real Anthony Fauci, lays out their corrupt partnership. It is a horrifying catalog of abuses.

[PA Presbyterian]

I’ve read that nurses are calling it, “Run, death is near.” At least two members of my church were put on it in the local hospital while they were on respirators being treated for COVID. They both died of organ failure, including the destruction of their kidneys. One was put on dialysis before he died.

[Captain Peter Blood]

That kills people, it’s toxic, and causes Kidney and total renal failure in up to 1/3 of the people it’s given to/ It’s poison, $3000 a dose, costs $10 to make and pushed by Fauci cause he get a cut on the royalties. Developed for Ebola and it didn’t work for that either. Murder pure and simple

[Captain Peter Blood]

Costs $10 to make and they charge $3000 a dose

[Captain Peter Blood]

It’s not even marginally effective, it’s 10 times as toxic as Chemo, it’s nothing but poison and it will kill kids.

[9YearLurker]

Yes—and it’s a killer. They probably finally realized they could rope more victims into the hospital this way.

[WWG1WWA]

Fauci owns the patent for Remdesivir.

[lonestar]

I had a friend who died on it. A[so had kidney failure and was on a ventilator.

[catnipman]

remdesivir is one NASTY drug (plus multiple studies have all shown it basically does NOT work: Adverse Effects >10% eGFR decreased* (18%) Decreased CrCl* (calculated by Cockcroft-Gault) (10-18%) Creatinine increased* (5-15%) Hemoglobin decreased* (6-15%) Glucose increased* (11-12%) Lymphocytes decreased* (11%) 1-10% Prothrombin time increased (9%) ALT increased* (3-8%) AST increased* (6-7%) Nausea (3-5%) Bilirubin increased* (2%) Hypersensitivity reactions (<2%) Generalized seizure (<2%) Rash (<2%) Next: Warnings Contraindications Hypersensitivity to drug or any ingredient Cautions Hypersensitivity, including infusion-related reactions Hypersensitivity, including infusion-related reactions observed during and following administration; most occur within 1 hr of administration Signs and symptoms may include hypotension, hypertension, tachycardia, bradycardia, hypoxia, fever, dyspnea, wheezing, angioedema, rash, nausea, diaphoresis, and shivering Consider slowing infusion rate (up to 120 minutes) to potentially prevent these signs and symptoms; observe patient for 1 hr after completing administration If clinically significant reaction occurs, discontinue immediately and implement appropriate treatment Hepatic transaminases Increased hepatic transaminases reported in healthy volunteers and patients with COVID-19 Because transaminase elevations are reported as a clinical feature of COVID-19, and the incidence in clinical trials was similar in patients receiving placebo versus remdesivir, it is challenging to discern the contribution of remdesivir to transaminase elevations in patients with COVID-19 ALT levels increase to >10x ULN: Consider discontinuing remdesivir ALT elevation accompanied by signs or symptoms of liver inflammation: Discontinue remdesivir Drug interaction overview Drug-drug interaction trials of remdesivir and other concomitant medications have not been conducted in humans In vitro, remdesivir is a substrate of CYP2C8, CYP2D6, and CYP3A4 enzymes; and a substrate of OAPT1B1 and P-glycoprotein transporters In vitro, remdesivir is an inhibitor of CYP3A4, OATP1B1, OATP1B3, BSEP, MRP4, and NTCP Clinical relevance of these in vitro assessments has not been established Coadministration with chloroquine or hydroxychloroquine Coadministration of remdesivir is not recommended with chloroquine or hydroxychloroquine Based on in vitro data, chloroquine demonstrated an antagonistic effect on the intracellular metabolic activation and antiviral activity of remdesivir Next: Pregnancy & Lactation Pregnancy There is a pregnancy exposure registry that monitors pregnancy outcomes in individuals exposed to the drug during pregnancy; pregnant and recently pregnant individuals can go to https://covid-pr.pregistry.com to enroll or call 1-800-616-3791 to obtain information about the registry Available data from published case reports and compassionate use of remdesivir in pregnant women are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes Animal studies In nonclinical reproductive toxicity studies, remdesivir demonstrated no adverse effect on embryofetal development when administered to pregnant animals at systemic exposures of the predominant circulating metabolite of remdesivir (GS-441524) that were 4 times (rats and rabbits) the exposure in humans at the recommended human dose Clinical considerations There are maternal and fetal risks associated with untreated COVID-19 in pregnancy; COVID-19 in pregnancy is associated with adverse maternal and fetal outcomes, including preeclampsia, eclampsia, preterm birth, premature rupture of membranes, venous thromboembolic disease, and fetal death Lactation Data are not available regarding the presence of remdesivir in human milk, effects on breastfed infants, or effects on milk production Animal studies Remdesivir and metabolites detected in plasma of nursing rat pups, likely owing to presence of remdesivir in milk following daily IV remdesivir to pregnant rats from gestation day 6 to lactation day 20 Exposures in nursing pups were ~1% that of maternal exposure on lactation day 10 Pregnancy Categories A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk. B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available. Next: Pharmacology Mechanism of Action Inhibits SARS-CoV-2 RNA-dependent RNA polymerase (RdRp), which is essential for viral replication 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 (RDV-TP) demonstrated in multiple cell types RDV-TP 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 '

[catnipman]

i give up ... can’t cut and paste text without losing linefeeds ...

[catnipman]

Adverse Effects

>10%

eGFR decreased* (18%)

Decreased CrCl* (calculated by Cockcroft-Gault) (10-18%)

Creatinine increased* (5-15%)

Hemoglobin decreased* (6-15%)

Glucose increased* (11-12%)

Lymphocytes decreased* (11%)

1-10%

Prothrombin time increased (9%)

ALT increased* (3-8%)

AST increased* (6-7%)

Nausea (3-5%)

Bilirubin increased* (2%)

Hypersensitivity reactions (<2%)

Generalized seizure (<2%)

Rash (<2%)

Next:

Warnings

Contraindications

Hypersensitivity to drug or any ingredient

Cautions

Hypersensitivity, including infusion-related reactions

Hypersensitivity, including infusion-related reactions observed during and following administration; most occur within 1 hr of administration

Signs and symptoms may include hypotension, hypertension, tachycardia, bradycardia, hypoxia, fever, dyspnea, wheezing, angioedema, rash, nausea, diaphoresis, and shivering

Consider slowing infusion rate (up to 120 minutes) to potentially prevent these signs and symptoms; observe patient for 1 hr after completing administration

If clinically significant reaction occurs, discontinue immediately and implement appropriate treatment

Hepatic transaminases

Increased hepatic transaminases reported in healthy volunteers and patients with COVID-19

Because transaminase elevations are reported as a clinical feature of COVID-19, and the incidence in clinical trials was similar in patients receiving placebo versus remdesivir, it is challenging to discern the contribution of remdesivir to transaminase elevations in patients with COVID-19

ALT levels increase to >10x ULN: Consider discontinuing remdesivir

ALT elevation accompanied by signs or symptoms of liver inflammation: Discontinue remdesivir

Drug interaction overview

Drug-drug interaction trials of remdesivir and other concomitant medications have not been conducted in humans

In vitro, remdesivir is a substrate of CYP2C8, CYP2D6, and CYP3A4 enzymes; and a substrate of OAPT1B1 and P-glycoprotein transporters

In vitro, remdesivir is an inhibitor of CYP3A4, OATP1B1, OATP1B3, BSEP, MRP4, and NTCP

Clinical relevance of these in vitro assessments has not been established

Coadministration with chloroquine or hydroxychloroquine

Coadministration of remdesivir is not recommended with chloroquine or hydroxychloroquine

Based on in vitro data, chloroquine demonstrated an antagonistic effect on the intracellular metabolic activation and antiviral activity of remdesivir

Next:

Pregnancy & Lactation

Pregnancy

There is a pregnancy exposure registry that monitors pregnancy outcomes in individuals exposed to the drug during pregnancy; pregnant and recently pregnant individuals can go to https://covid-pr.pregistry.com to enroll or call 1-800-616-3791 to obtain information about the registry

Available data from published case reports and compassionate use of remdesivir in pregnant women are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes

Animal studies

In nonclinical reproductive toxicity studies, remdesivir demonstrated no adverse effect on embryofetal development when administered to pregnant animals at systemic exposures of the predominant circulating metabolite of remdesivir (GS-441524) that were 4 times (rats and rabbits) the exposure in humans at the recommended human dose

Clinical considerations

There are maternal and fetal risks associated with untreated COVID-19 in pregnancy; COVID-19 in pregnancy is associated with adverse maternal and fetal outcomes, including preeclampsia, eclampsia, preterm birth, premature rupture of membranes, venous thromboembolic disease, and fetal death

Lactation

Data are not available regarding the presence of remdesivir in human milk, effects on breastfed infants, or effects on milk production

Animal studies

Remdesivir and metabolites detected in plasma of nursing rat pups, likely owing to presence of remdesivir in milk following daily IV remdesivir to pregnant rats from gestation day 6 to lactation day 20

Exposures in nursing pups were ~1% that of maternal exposure on lactation day 10

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Next:

Pharmacology

Mechanism of Action

Inhibits SARS-CoV-2 RNA-dependent RNA polymerase (RdRp), which is essential for viral replication

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 (RDV-TP) demonstrated in multiple cell types

RDV-TP 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

'