Remote-control assisted-suicide.
Clinical Pharmacology & Therapeutics, April 2021. This is the flagship journal of the American Society for Clinical Pharmacology and Therapeutics.
Abstract
Remdesivir is approved for emergency use by the US Food and Drug Administration (FDA) and authorized conditionally by the European Medicines Agency (EMA) for patients with coronavirus disease 2019 (COVID-19). Its benefit-risk ratio is still being explored because data in the field are rather scant. A decrease of the creatinine clearance associated with remdesivir has been inconstantly reported in clinical trials with unclear relevance. Despite these uncertainties, we searched for a potential signal of acute renal failure (ARF) in pharmacovigilance postmarketing data. An analysis of the international pharmacovigilance postmarketing databases (VigiBase) of the World Health Organization (WHO) was performed, using two disproportionality methods. Reporting odds ratio (ROR) compared the number of ARF cases reported with remdesivir, with those reported with other drugs prescribed in comparable situations of COVID-19 (hydroxychloroquine, tocilizumab, and lopinavir/ritonavir). The combination of the terms "acute renal failure" and "remdesivir" yielded a statistically significant disproportionality signal with 138 observed cases instead of the 9 expected. ROR of Acute Renal Failure (ARF) with remdesivir was 20-fold (20.3; confidence interval 0.95 [15.7-26.3], P < 0.0001]) that of comparative drugs. Based on ARF cases reported in VigiBase, and despite the caveats inherent to COVID-19 circumstances, we detected a statistically significant pharmacovigilance signal of nephrotoxicity associated with remdesivir, deserving a thorough qualitative assessment of all available data. Meanwhile, as recommended in its Summary of Product Characteristics, assessment of patients with COVID-19 renal function should prevail before and during treatment with remdesivir in COVID-19.
What I know about remdesivir, could be etched on the head of a straight pin and leave a lot of room on the head of the pin.
Last year, two people, we know and who didn’t know each other received this drug on an experimental trial basis, and in a few days left the Covid ICU in our local hospital.
They are approaching their one year anniversary re remdesivir in a few months.
One is an over 80 year old guy, who needed to lose 40#’s.
He was given this drug in the hospital, and, he was discharged from the hospital after a couple of days later. One of his daughters, an RN completed the course of therapy in her home, where he now lives. A couple of weeks later he got a pace maker and is doing well.
The other patient is a late 40 something woman. She passed out while being driven home from the school, where she was a teacher. She was admitted to the same hospital/ER/Covid ICU, and she was treated with remdesivir and was discharged. She was being considered for a pacemaker before the covid. She had a pace maker installed about 2 weeks later as an outpatient.
She is in her words, “Better than ever, post pacemaker!”
I bet they do. How much will Fauchi make now?
When the worm turns and its time to take heads of the guilty...
Any doctor prescribing remdesivir should be arrested and tried for attempted murder. And if the patient does die, murder in the first.
The information against remdesivir is widely enough available that no doctor can have “I didn’t know” as an excuse.
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
Fauci owns the patent for Remdesivir.
i give up ... can’t cut and paste text without losing linefeeds ...
>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
'