Remdesivir Injection

 

Remdesivir is an intravenous nucleotide of an adenosine analogue. The remedivator binds to viral RNA-dependent RNA polymerase and inhibits viral replication by premature termination of RNA transcription. It has been shown in in vitro activity against SARS-COV-2.1 In a Rhesus Mack model of SARS-COV-2 infection, treatment of the remixer was initiated immediately after injection; Remediator-treated animals had lower levels of the virus in their lungs and less lung damage than control animals.

 

Remediators have been approved by the Food and Drug Administration (FDA) for the treatment of hospitalized adult and pediatric patients (under 12 years of age and weighing ≥40 kg). It is also available by FDA Emergency Use Authority (EUA) for the treatment of Kovid-19 in hospitalized pediatric patients ranging from 3.5 kg to <40 kg or 12 years of age and weighing .55.5 kg. The remediator should be installed in a hospital or health care system that can provide the same level of care to a patient's hospital.

 

Remedivasives have been studied in several clinical trials for the treatment of COVID-19. The recommendations of the Covid-19 treatment guidelines panel are based on the results of these studies. Refer to Table 2a for more information.

 

The safety and efficacy of combination therapy with remedesivir with corticosteroids have not been rigorously studied in clinical trials; However, there are theoretical reasons that combination therapy may be helpful in some patients with severe COVID-19. For panel recommendations on the use of remedicator with or without demacethesone in some hospitalized patients, see Treatment Management for Patients with Covid-19.

 

Monitoring and adverse effects

Remedacivir can cause gastrointestinal symptoms (e.g., nausea), elevated levels of elevated transaminases, increased prothrombin time (without changes in the international normal ratio) and hypersensitivity.

 

Liver function tests and prothrobin timing should be obtained in all patients before administering remedicivir and during clinically prescribed treatment. The remediator may need to be discontinued if the level of alanine transaminase (ALT) is 10 times higher than normal and should be discontinued if there is an increase in the level of ALT and symptoms of hepatitis. Is seen.

 

Considerations in patients with renal insufficiency

Each 100 mg vial of Remdesivir lyophilized powder contains 3g of sulfobutyle beta-cyclodextrin sodium (SBECD), while every 100 mg / 20 ml. The remedial solution contains 6 g SBECD.3 SBECD is a vehicle that is excreted primarily by the kidneys. A patient with Kovid-19 who receives a loaded dose of 200 mg of Ramdesivir will receive 6 g to 12 g of SBECD, depending on the formula. This amount of SBECD is within the safety precautions for patients with normal renal function. Accumulation of SBECD in patients with renal impairment may result in liver and renal toxicity. Clinicians may consider the use of lyophilized powdered formulations (which are low in SBECD) in patients with renal impairment.

 

Because both remedial formulas contain SBECD, <50 ml. Patients with an approximate glomerular filtration rate (EGFR) of / min have been excluded from some clinical trials of Remedesivar; In other trials <30 ml. / Min was an EGFR cutoff. EGFR <30 ml. Remedicator is not recommended for patients due to lack of data per minute. Renal function should be monitored as prescribed clinically before and during renal device therapy.

 

In two surveillance studies that evaluated the use of remedicivir in hospitalized patients with COVD-19, an estimated creatinine clearance (CRCL) <30 ml. There were no significant differences in the incidence of side effects or severe kidney injury in patients with / min. With an estimated CRCL of ≥30 mL / min.6,7, one of these studies evaluated patients who primarily prepared a solution of remedacivir (20 patients had an estimated CRCL of <30 ml / min and An estimated CRCL at 115 ≥30 mL / min.); 6 Other studies evaluated patients who received a lyophilized powder powder formulation (40 patients had an estimated CRCL <30 ml / min and 307 had an estimated CRCL ≥30 ml / min.7)

 

Drug-drug interactions

Clinical drug-drug interactions of remedial have not been studied. In vitro, rimadesivir is a substrate of cytochrome P450 (CYP) 3A4 and the drug transporter's organic anion-translating polypeptide (OATP) 1B1 and p-glycoprotein. It is also an inhibitor of CYP3A4, OATP1B1, OATP1B3, and the multidrug and toxin extrusion protein 1 (MAT1) .3.

 

According to information provided by Gilead Sciences (Written Communication, July 2020), when remedesivir is administered with dexamethasone, remedesivar exposure is expected to be minimal. Chlorquine or hydroxychloroquine may reduce the antiviral activity of the remediator; According to information provided by Gilead Sciences (written communication, August and September 2020), the coordination of these drugs is not recommended. Remdesivir is not expected to have any significant interactions with Oseltamivir or Baloxavir.

 

Considerations inpregnancy

Pregnant patients were excluded from clinical trials that assessed the safety and efficacy of remedicators for the treatment of COVID-19, but reports of remedicator use in pregnant patients from the remedicator compassionate use program are reliable.

Of the 86 patients admitted to the hospital for serious pregnancy and postpartum, patients with severe covid-1 who received sympathetic remediators, the therapy was well tolerated, with a very low incidence of adverse events.

Remedacivir should not be discontinued from pregnant patients if it is indicated.

Thoughts in children

The safety and efficacy of the use of remedivir for the treatment of COVID-19 have not been evaluated in pediatric patients aged 12 years and under 40 kg.

Remdesivir is a weight loss of 3.5 kg to <40 kg or 12 years of age or .53.5 kg in pediatric patients admitted to the hospital for treatment of CFDA 19 by an FDA EUA.

A clinical trial is currently evaluating the pharmacokinetics of remedicivir in children (Clinical Trials.gov Identifier NCT 04431453).

Clinical trials

Several clinical trials evaluating the use of remediators for the treatment of COVID-19 are currently underway or in development. Please see Clinical Trials.gov for the latest information. Considerations in patients with renal insufficiency

Each 100 mg vial of Remdesivir lyophilized powder contains 3 g of sulfobutyle beta-cyclodextrin sodium (SBECD), while every 100 mg / 20 ml. The remedial solution contains 6 g SBECD.3 SBECD is a vehicle that is excreted primarily by the kidneys. A patient with Kovid-19 who receives a loaded dose of 200 mg of Ramdesivir will receive 6 g to 12 g of SBECD, depending on the formula. This amount of SBECD is within the safety precautions for patients with normal renal function. Accumulation of SBECD in patients with renal impairment may result in liver and renal toxicity. Clinicians may consider the use of lyophilized powdered formulations (which are low in SBECD) in patients with renal impairment.

 

Because both remedial formulas contain SBECD, <50 ml. Patients with an approximate glomerular filtration rate (EGFR) of / min have been excluded from some clinical trials of Remedesivar; In other trials <30 ml. / Min was an EGFR cutoff. EGFR <30 ml. Remedicator is not recommended for patients due to lack of data per minute. Renal function should be monitored as prescribed clinically before and during renal device therapy.

 

In two surveillance studies that evaluated the use of remedicivir in hospitalized patients with COVD-19, an estimated creatinine clearance (CRCL) <30 ml. There were no significant differences in the incidence of side effects or severe kidney injury in patients with / min. With an estimated CRCL of ≥30 mL / min.6,7, one of these studies evaluated patients who primarily prepared a solution of remedacivir (20 patients had an estimated CRCL of <30 ml / min and An estimated CRCL at 115 ≥30 mL / min.); 6 Other studies evaluated patients who received a lyophilized powder powder formulation (40 patients had an estimated CRCL <30 ml / min and 307 had an estimated CRCL ≥30 ml / min.7)

 

Drug-drug interactions

Clinical drug-drug interactions of remedial have not been studied. In vitro, rimadesivir is a substrate of cytochrome P450 (CYP) 3A4 and the drug transporter's organic anion-translating polypeptide (OATP) 1B1 and p-glycoprotein. It is also an inhibitor of CYP3A4, OATP1B1, OATP1B3, and the multidrug and toxin extrusion protein 1 (MAT1) .3.

 

According to information provided by Gilead Sciences (Written Communication, July 2020), when remedesivir is administered with dexamethasone, remedesivar exposure is expected to be minimal. Chlorquine or hydroxychloroquine may reduce the antiviral activity of the remediator; According to information provided by Gilead Sciences (written communication, August and September 2020), the coordination of these drugs is not recommended. Remdesivir is not expected to have any significant interactions with Oseltamivir or Baloxavir.

 

Considerations inpregnancy

Pregnant patients were excluded from clinical trials that assessed the safety and efficacy of remedicators for the treatment of COVID-19, but reports of remedicator use in pregnant patients from the remedicator compassionate use program are reliable.

Of the 86 patients admitted to the hospital for serious pregnancy and postpartum, patients with severe covid-1 who received sympathetic remediators, the therapy was well tolerated, with a very low incidence of adverse events.

Remedacivir should not be discontinued from pregnant patients if it is indicated.

Thoughts in children

The safety and efficacy of the use of remedivir for the treatment of COVID-19 have not been evaluated in pediatric patients aged 12 years and under 40 kg.

Remdesivir is a weight loss of 3.5 kg to <40 kg or 12 years of age or .53.5 kg in pediatric patients admitted to the hospital for treatment of CFDA 19 by an FDA EUA.

A clinical trial is currently evaluating the pharmacokinetics of remedicivir in children (Clinical Trials.gov Identifier NCT 04431453).

Clinical trials

Several clinical trials evaluating the use of remediators for the treatment of COVID-19 are currently underway or in development. Please see Clinical Trials.gov for the latest information.