In this episode, I’ll discuss the remdesivir emergency use prescribing information as it pertains to adult patients.
Remdesivir is a viral RNA inhibitor which just received an emergency use authorization from the FDA for the treatment of COVID-19.
For adult patients there are two different suggested dosage regimens:
The suggested dose for adults and pediatric patients weighing ≥40 kg requiring invasive mechanical ventilation and/or ECMO is a single loading dose of 200 mg infused intravenously over 30 to 120 minutes on Day 1 followed by once-daily maintenance doses of 100 mg infused intravenously over 30 to 120 minutes for 9 days (days 2 through 10).
and
The suggested dose for adults and pediatric patients weighing ≥40 kg not requiring invasive mechanical ventilation and/or ECMO is a single dose of 200 mg infused intravenously over 30 to 120 minutes on Day 1 followed by once-daily maintenance doses of 100 mg infused intravenously over 30 to 120 minutes for 4 days (days 2 through 5). If a patient does not demonstrate clinical improvement, treatment may be extended for up to 5 additional days (i.e., up to a total of 10 days).
A diagnosis of COVID-19 is not required to start remdesivir; it may be started in hospitalized patients with suspected COVID-19 pending laboratory confirmation of infection.
Regarding renal dose adjustment:
All patients must have an estimated glomerular filtration rate (eGFR) determined before dosing. Remdesivir is not recommended in adult and pediatric patients (>28 days old) with eGFR less than 30 mL/min or in full-term neonates (≥7 days to ≤28 days old) with serum creatinine greater than or equal to 1 mg/dL unless the potential benefit outweighs the potential risk. Patients with eGFR greater than or equal to 30 mL/min have received remdesivir for treatment of COVID-19 with no dose adjustment of remdesivir.
Regarding routine lab monitoring:
The following laboratory tests should be performed daily while receiving remdesivir: serum chemistries, hematology, ALT, AST, bilirubin, and alkaline phosphatase; renal function tests (creatinine and creatinine clearance)
Regarding administration:
The prepared diluted solution should not be administered simultaneously with any other medication. The compatibility of remdesivir injection with IV solutions and medications other than saline is not known.
Administration may occur over 30 to 120 minutes. After infusion is complete, the EAU prescribing information suggests to flush the IV with at least 30 mL of normal saline.
Remdesivir is available in both a powder for reconstitution and an injectable solution. There is no preservative or bacteriostatic agent present in remdesivir.
Remdesivir is diluted before administration with normal saline. The recommendation is to gently invert the bag 20 times to mix the solution in the bag. The solution should not be shaken so presumably it should not be delivered by pneumatic tube.
The diluted remdesivir solution for infusion can be stored up to 4 hours at room temperature (20°C to 25°C [68°F to 77°F]) or 24 hours at refrigerated temperature (2°C to 8°C [36°F to 46°F]).
Regarding adverse events:
Infusion-related reactions have been observed during, and/or have been temporally associated with, administration of remdesivir. Signs and symptoms may include hypotension, nausea, vomiting, diaphoresis, and shivering.
Transaminase elevations have been observed in the remdesivir clinical development program, including in healthy volunteers and patients with COVID19. In healthy volunteers who received up to 150 mg daily for 14 days, alanine aminotransferase (ALT) elevations were observed in the majority of patients, including elevations up to 10 times baseline values in one subject without evidence of clinical hepatitis;
Transaminase elevations have also been reported in patients with COVID-19 who received remdesivir, including one patient with ALT elevation up to 20 times the upper limit of normal. As transaminase elevations have been reported as a component of COVID-19 in some patients, discerning the contribution of remdesivir to transaminase elevations in this patient population is challenging.
In response to hepatic testing:
Remdesivir should not be initiated in patients with ALT ≥ 5 times the upper limit of normal at baseline. Remdesivir should be discontinued in patients who develop:
ALT ≥ 5 times the upper limit of normal during treatment with remdesivir. Remdesivir may be restarted when ALT is < 5 times the upper limit of normal. OR ALT elevation accompanied by signs or symptoms of liver inflammation or increasing conjugated bilirubin, alkaline phosphatase, or INR.
The completion of an FDA MedWatch Form to report all medication errors and serious adverse events with remdesivir is considered mandatory.
Regarding interactions:
Drug-drug interaction trials of remdesivir and other concomitant medications have not been conducted in humans. In vitro, remdesivir is a substrate for drug metabolizing enzymes CYP2C8, CYP2D6, and CYP3A4, and is a substrate for Organic Anion Transporting Polypeptides 1B1 (OAPT1B1) and P-glycoprotein (Pgp) transporters. In vitro, remdesivir is an inhibitor of CYP3A4, OATP1B1, OATP1B3, BSEP, MRP4, and NTCP. The clinical relevance of these in vitro assessments has not been established.
You can read the full emergency use authorization prescribing information at this link.
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