Remdesivir (Systemic)

Drug class: Antineoplastic Agents

Usage of Remdesivir (Systemic)

Coronavirus Disease 2019 (COVID-19)

Treatment of COVID-19 caused by SARS-CoV-2 in adults and pediatric patients 28 days of age and older weighing ≥3 kg who are hospitalized or who are not hospitalized but have mild-to-moderate COVID-19 with high risk for progression to severe COVID-19, including hospitalization and death.

NIH COVID-19 Treatment Guidelines Panel states that remdesivir is recommended for treatment of COVID-19 in hospitalized patients who do not require oxygen supplementation but are at high risk of progressing to severe COVID-19 as well as those requiring conventional oxygen. In hospitalized patients who do not require oxygen supplementation, the Panel recommends that remdesivir therapy be given early in disease course (e.g., within 10 days of symptom onset) for greatest benefit. For most hospitalized patients who require conventional oxygen, the Panel recommends administration of remdesivir plus dexamethasone, with dexamethasone alone an appropriate option if remdesivir cannot be obtained. IDSA guidelines on the treatment and management of patients with COVID-19 recommend the initiation of remdesivir within 7 days of symptom onset in hospitalized patients with mild-to-moderate COVID-19 at high risk for progression to severe disease. For hospitalized patients on supplemental oxygen, the IDSA Panel suggests treatment with 5 versus 10 days of remdesivir and in those with severe COVID-19 (defined as a SpO2 ≤94% on room air) the guideline suggests remdesivir over no antiviral treatment. Routine use of remdesivir in hospitalized patients with COVID-19 on invasive ventilation and/or ECMO is not recommended.

The NIH COVID-19 Treatment Guidelines Panel recommends use of ritonavir-boosted nirmatrelvir or remdesivir (in order of preference) for outpatients with mild to moderate COVID-19 who do not require supplemental oxygen but who are at high risk of progressing to severe disease. IDSA guidelines suggest that outpatients with mild-to-moderate COVID-19 at high risk for progression to severe disease be administered remdesivir within 7 days of symptom onset rather than no remdesivir. Options for treatment in these patients include nirmatrelvir/ritonavir, 3-day treatment with remdesivir, molnupiravir, and neutralizing monoclonal antibodies. Choice of agent should be driven by product availability, institutional capacity and infrastructure, and patient-specific factors (e.g., patient age, symptom duration, renal function, drug interactions).

Consult the most recent NIH and IDSA COVID-19 treatment guidelines for additional information.

Relate drugs

How to use Remdesivir (Systemic)

General

Pretreatment Screening

  • Perform hepatic laboratory testing in all patients prior to initiating therapy.
  • Assess prothrombin time (PT) prior to intiating therapy.

    • Patient Monitoring

  • Monitor patients during infusion and observe patients for at least 1 hour after infusion is complete for signs and symptoms of hypersensitivity.
  • Perform hepatic laboratory testing during therapy as appropriate.
  • Monitor PT as clinically appropriate during therapy.

    • Dispensing and Administration Precautions

  • Administer only in settings where healthcare providers have immediate access to medications used to treat severe infusion or hypersensitivity reactions, such as anaphylaxis, and the ability to activate the emergency medication system (EMS) as necessary.

    • Administration

    Administer only by IV infusion. Do not give by any other route.

    Do not administer simultaneously with any other IV drugs.

    Compatible with 0.9% sodium chloride injection; compatibility with other IV solutions or drugs not known.

    Do not shake remdesivir solutions. Manufacturer states do not use pneumatic tube systems to transport or deliver IV infusion bags containing remdesivir; studies not conducted to assess effects of vigorous shaking or vibration on the drug.

    After the IV infusion of remdesivir completed, flush infusion line with sufficient volume of 0.9% sodium chloride to ensure delivery of entire dose.

    Discard solution if discolored or contains particulates.

    Does not contain preservatives or bacteriostatic agents. Discard unused lyophilized powder, solution concentrate, or diluted solutions of the drug; do not reuse or save for future use.

    IV Infusion

    Available in 2 different formulations: lyophilized powder in single-dose vials containing 100 mg of remdesivir that must be reconstituted with sterile water for injection prior to diluting with 0.9% sodium chloride injection, and a solution concentrate in single-dose vials containing 100 mg/20 mL (5 mg/mL) that must be further diluted in 0.9% sodium chloride injection prior to infusion.

    Carefully follow product-specific preparation instructions for each formulation.

    Lyophilized powder formulation is the only approved dosage form for pediatric patients weighing 3 kg to <40 kg.

    Preparation of Lyophilized Powder in Adults and Pediatric Patients Weighing ≥40 kg

    Reconstitute lyophilized powder and further dilute prior to IV infusion.

    Reconstitute single-dose vial containing 100 mg of lyophilized remdesivir by adding 19 mL of sterile water for injection and immediately shaking vial for 30 seconds. Allow vial contents to settle for 2–3 minutes, resulting in a clear, colorless to yellow, solution. If vial contents do not completely dissolve, repeat this process as necessary until drug completely dissolves. Discard vial if contents do not dissolve completely.

    Reconstituted solution contains 100 mg/20 mL (5 mg/mL). Further dilute in a 100- or 250-mL IV infusion bag containing 0.9% sodium chloride injection prior to IV infusion.

    Prior to transferring required volume of reconstituted remdesivir solution to the IV infusion bag, withdraw appropriate volume of 0.9% sodium chloride from the IV bag (using an appropriately sized syringe and needle) and discard (see Table 1).

    After adding appropriate volume of reconstituted remdesivir to the IV bag, mix by gently inverting bag 20 times; do not shake.

    Table 1. Reconstituted Lyophilized Powder: Dilution Instructions for Preparing Loading Dose (200 mg) and Maintenance Doses (100 mg) of Remdesivir for Adults and Pediatric Patients ≥12 Years of Age Weighing ≥40 kg.1

    Remdesivir Dose (mg)

    Initial Volume of 0.9% Sodium Chloride in IV Infusion Bag (mL)

    Volume of 0.9% Sodium Chloride to be Withdrawn from IV Infusion Bag and Discarded (mL)

    Volume of Reconstituted Remdesivir to be Transferred into IV Infusion Bag of 0.9% Sodium Chloride (mL)

    200 (2 vials containing 100 mg)

    250

    40

    40 (2 × 20)

    100

    40

    40 (2 × 20)

    100 (1 vial containing 100 mg)

    250

    20

    20

    100

    20

    20

    Preparation of Lyophilized Powder in Pediatric Patients Weighing 3 to <40 kg

    Reconstitute lyophilized powder and further dilute prior to IV infusion.

    Reconstitute single-dose vial containing 100 mg of lyophilized remdesivir by adding 19 mL of sterile water for injection and immediately shaking vial for 30 seconds. Allow vial contents to settle for 2–3 minutes, resulting in a clear, colorless to yellow, solution. If vial contents do not completely dissolve, repeat this process as necessary until drug completely dissolves. Discard vial if contents do not dissolve completely.

    Reconstituted solution contains 100 mg/20 mL (5 mg/mL). Further dilute in 0.9% sodium chloride injection to a fixed concentration of 1.25 mg/mL prior to IV infusion.

    Calculate total required infusion volume of diluted remdesivir solution containing 1.25 mg/mL based on the pediatric weight-based dosing regimen of 5 mg/kg for loading dose or 2.5 mg/kg for maintenance doses.

    Use a small IV infusion bag (e.g., 25, 50, or 100 mL) or an appropriately sized syringe to administer remdesivir solutions in pediatric patients weighing 3 to <40 kg; a syringe and syringe pump may be used to deliver volumes <50 mL. Administer recommended dose via IV infusion in a total infusion volume based on the indicated dose and calculated to yield the target remdesivir concentration of 1.25 mg/mL.

    Instructions for use of an IV infusion bag:Use an appropriately sized small IV bag (either prefilled with 0.9% sodium chloride or empty). If using prefilled IV bag, withdraw appropriate volume of 0.9% sodium chloride based on patient's dose plus a quantity sufficient to achieve a final 1.25-mg/mL concentration from the bag and discard; then withdraw required volume of reconstituted remdesivir solution containing 100 mg/20 mL (5 mg/mL) from the vial (using an appropriately sized syringe and needle) and transfer into the IV bag containing 0.9% sodium chloride. If using empty IV bag, withdraw required volume of reconstituted remdesivir solution containing 100 mg/20 mL (5 mg/mL) from the vial (using an appropriately sized syringe and needle) and transfer into the IV bag, then add appropriate volume of 0.9% sodium chloride sufficient to achieve a final concentration of 1.25 mg/mL to the bag. Mix by gently inverting bag 20 times; do not shake. The prepared infusion solution is stable for 24 hours at room temperature (20–25°C) or 48 hours in the refrigerator (2–8°C).

    Instructions for use of a syringe:Select an appropriately sized syringe for administration that is equal to or larger than the calculated total infusion volume of the 1.25-mg/mL remdesivir solution that is required for the dose. Using the administration syringe, withdraw required volume of reconstituted remdesivir solution containing 100 mg/20 mL (5 mg/mL) from the vial into the syringe followed by the required volume of 0.9% sodium chloride needed to achieve a final remdesivir solution containing 1.25 mg/mL. Mix by gently inverting the syringe 20 times; do not shake. Use the prepared diluted solution immediately.

    Preparation of Solution Concentrate for Adults and Pediatric Patients Weighing ≥40 kg

    Must dilute solution concentrate prior to IV infusion.

    Remdesivir solution concentrate contains 100 mg/20 mL (5 mg/mL). Must dilute in a 250-mL IV infusion bag containing 0.9% sodium chloride injection.

    Allow vials of the solution concentrate to equilibrate to room temperature prior to dilution.

    Prior to transferring required volume of remdesivir solution concentrate to the IV infusion bag containing 0.9% sodium chloride, withdraw appropriate volume of 0.9% sodium chloride from the IV bag (using an appropriately sized syringe and needle) and discard. (See Table 2.)

    After adding appropriate volume of remdesivir solution concentrate to the IV bag containing 0.9% sodium chloride, mix by gently inverting bag 20 times; do not shake.

    The prepared infusion solution is stable for 24 hours at room temperature (20–25°C) or 48 hours at refrigerated temperature (2–8°C).

    Table 2. Reconstituted Lyophilized Powder: Dilution Instructions for Preparing Loading Dose (200 mg) and Maintenance Doses (100 mg) of Remdesivir for Pediatric Patients <12 Years of Age Weighing ≥40 kg†.26

    Remdesivir Dose (mg)

    Initial Volume of 0.9% Sodium Chloride in IV Infusion Bag (mL)

    Volume of 0.9% Sodium Chloride to be Withdrawn from IV Infusion Bag and Discarded (mL)

    Volume of Reconstituted Remdesivir to be Transferred into IV Infusion Bag of 0.9% Sodium Chloride (mL)

    200 (2 vials containing 100 mg)

    250

    40

    40 (2 × 20)

    100

    40

    40 (2 × 20)

    100 (1 vial containing 100 mg)

    250

    20

    20

    100

    20

    20

    Rate of Administration

    Adults and pediatric patients weighing ≥40 kg: Administer IV infusions over 30–120 minutes. For recommended IV infusion rate when administering remdesivir prepared using the lyophilized powder or solution concentrate, see Table 3.

    Pediatric patients weighing 3 to <40 kg: Infuse diluted solution over 30 to 120 minutes. Calculate the rate of infusion (mL/minute) based on the total infusion volume and total infusion time.

    Table 3. Recommended Rate of IV Infusion in Adults and Pediatric Patients Weighing ≥40 kg.1

    Infusion Bag Volume (mL)

    Infusion Time (minutes)

    Infusion Rate (mL/minute)

    250

    (prepared using lyophilized powder or solution concentrate)

    30

    8.33

    250

    (prepared using lyophilized powder or solution concentrate)

    60

    4.17

    250

    (prepared using lyophilized powder or solution concentrate)

    120

    2.08

    100

    (prepared using lyophilized powder)

    30

    3.33

    100

    (prepared using lyophilized powder)

    60

    1.67

    100

    (prepared using lyophilized powder)

    120

    0.83

    Dosage

    Pediatric Patients

    Coronavirus Disease 2019 (COVID-19) Pediatric Patients ≥28 Days of Age IV

    Hospitalized pediatric patients weighing ≥40 kg: Remdesivir loading dose of 200 mg by IV infusion on day 1, followed by maintenance doses of 100 mg by IV infusion once daily starting on day 2. Recommended total treatment duration for hospitalized patients requiring mechanical ventilation and/or extracorporeal membrane oxygenation (ECMO) is 10 days. Recommended treatment duration for hospitalized patients not requiring invasive mechanical ventilation and/or ECMO is 5 days. If no clinical improvement, the drug may be continued at a dosage of 100 mg by IV infusion once daily for up to 5 additional days (i.e., up to a total treatment duration of 10 days).

    Hospitalized pediatric patients weighing 3 to <40 kg:Remdesivir loading dose of 5 mg/kg by IV infusion on day 1, followed by maintenance doses of 2.5 mg/kg by IV infusion once daily starting on day 2. Recommended total treatment duration for hospitalized patients requiring mechanical ventilation and/or ECMO is 10 days. Recommended treatment duration for hospitalized patients not requiring invasive mechanical ventilation and/or ECMO is 5 days. If there is no clinical improvement, may extend treatment for up to 5 additional days (i.e., up to a total treatment duration of 10 days). The lyophilized powder is the only approved dosage form for pediatric patients weighing 3 to <40 kg.

    Nonhospitalized pediatric patients weighing ≥40 kg:Initiate treatment course as soon as possible after diagnosis of symptomatic COVID-19 has been made and within 7 days of symptom onset. Recommended dosage consists of a remdesivir loading dose of 200 mg by IV infusion on day 1, followed by maintenance doses of 100 mg by IV infusion once daily starting on day 2. Recommended total treatment duration for nonhospitalized patients diagnosed with mild-to-moderate COVID-19 who are at high risk of progression to severe COVID-19 is 3 days.

    Nonhospitalized pediatric patients weighing 3 to <40 kg:Initiate treatment course as soon as possible after diagnosis of symptomatic COVID-19 has been made and within 7 days of symptom onset. Recommended dosage consists of a remdesivir loading dose of 5 mg/kg by IV infusion on day 1, followed by maintenance doses of 2.5 mg/kg by IV infusion once daily starting on day 2. Recommended total treatment duration for nonhospitalized patients diagnosed with mild-to-moderate COVID-19 who are at high risk of progression to severe COVID-19 is 3 days. The lyophilized powder is the only approved dosage form for pediatric patients weighing 3 to <40 kg.

    Adults

    Coronavirus Disease 2019 (COVID-19) IV

    Hospitalized patients: Loading dose of 200 mg by IV infusion on day 1, followed by maintenance doses of 100 mg by IV infusion once daily starting on day 2. Recommended total treatment duration for hospitalized patients requiring mechanical ventilation and/or ECMO is10 days. Recommended treatment duration for hospitalized patients not requiring invasive mechanical ventilation and/or ECMO is 5 days. If no clinical improvement, may continue at a dosage of 100 mg by IV infusion once daily for up to 5 additional days (i.e., up to a total treatment duration of 10 days).

    Nonhospitalized patients:Loading dose of 200 mg by IV infusion on day 1, followed by maintenance doses of 100 mg by IV infusion once daily starting on day 2. Initiate treatment course as soon as possible after diagnosis of symptomatic COVID-19 has been made and within 7 days of symptom onset. Recommended total treatment duration for nonhospitalized patients diagnosed with mild-to-moderate COVID-19 who are at high risk of progression to severe COVID-19 is 3 days.

    Special Populations

    Hepatic Impairment

    Pharmacokinetics not evaluated in patients with hepatic impairment.

    Renal Impairment

    No dosage adjustment is recommended in patients with any degree of renal impairment, including those on dialysis.

    Geriatric Patients

    Dosage adjustment not needed. Consider greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy observed in the elderly.

    Warnings

    Contraindications

  • History of clinically important hypersensitivity reactions to the drug or any ingredient in the formulation.

    • Warnings/Precautions

    Hypersensitivity and Infusion-related Reactions

    Hypersensitivity reactions, including infusion-related and anaphylactic reactions, observed during and following remdesivir administration. Signs and symptoms of such reactions may include hypotension, hypertension, tachycardia, bradycardia, hypoxia, fever, dyspnea, wheezing, angioedema, rash, nausea, diaphoresis, and shivering. Consider a slower rate of IV infusion, with a maximum infusion time of up to 120 minutes, to potentially prevent these signs and symptoms.

    Monitor during infusion and observe patients for at least 1 hour after infusion is complete for signs and symptoms of hypersensitivity. If signs and symptoms of a clinically important hypersensitivity reaction occur, immediately discontinue administration of remdesivir and initiate appropriate treatment.

    Increased Risk of Aminotransferase Elevations

    Aminotransferase elevations observed in healthy individuals who received remdesivir in phase 1 studies and also reported in patients with COVID-19 who received the drug.

    Assess hepatic function prior to and as clinically appropriate during remdesivir treatment.

    Consider discontinuing remdesivir in patients who develop ALT concentrations >10 times the ULN during treatment.

    Discontinue remdesivir in patients who develop elevated ALT concentrations accompanied by signs or symptoms of liver inflammation.

    Risk of Reduced Antiviral Activity if Used Concomitantly with Chloroquine or Hydroxychloroquine

    Concomitant use of remdesivir and chloroquine or hydroxychloroquine not recommended because of in vitro evidence that chloroquine antagonizes intracellular metabolic activation and antiviral activity of remdesivir.

    Specific Populations

    Pregnancy

    Available data have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes following exposure in the second or third trimester; however, insufficient data to evaluate risk in first trimester. There are maternal risks associated with untreated COVID-19 in pregnancy. In nonclinical reproductive toxicity studies, no adverse embryofetal effects demonstrated when administered to pregnant animals at systemic exposures higher than those associated with recommended human dose.

    Lactation

    Remdesivir and its active metabolite distribute into human milk; however, available data do not indicate adverse effects on the breastfed infant from exposure to the drug. No data on effects of the drug on milk production.

    Consider developmental and health benefits of breast-feeding along with the mother’s clinical need for remdesivir and any potential adverse effects on the breast-fed child from the drug or underlying maternal condition. Breastfeeding individuals with COVID-19 should follow clinical guidelines to avoid exposing the infant to the virus.

    Pediatric Use

    Safety and efficacy for treatment of COVID-19 established in pediatric patients ≥28 days of age weighing ≥3 kg. Use of remdesivir in pediatric patients with renal impairment is supported by safety data in adults. There are limited data in pediatric patients with mild to moderate renal impairment and no data in pediatric patients with severe renal impairment. The formulation contains the excipient betadex sulfobutyl ether sodium (sulfobutylether β-cyclodextrin sodium; SBECD) which, when administered IV, is eliminated through glomerular filtration and therefore when administered to pediatric patients with renal immaturity or renal impairment, may result in higher exposure to SBECD.

    Geriatric Use

    No differences in response identified between geriatric and younger patients. Although dosage adjustment not needed in patients >65 years of age, use appropriate caution and monitoring because of greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease or other drug therapy in the elderly.

    Hepatic Impairment

    Assess hepatic function prior to and as clinically appropriate during remdesivir treatment.

    Aminotransferase elevations observed in healthy individuals and patients with COVID-19 who received the drug.

    Renal Impairment

    Safety profile in patients with COVID-19 and renal impairment, including those on dialysis, consistent with those observed in clinical trials of the drug in adults. Exposures to drug's metabolites and SBECD are increased in patients with mild to severe renal impairment, including those requiring dialysis, relative to those with normal renal function.

    Common Adverse Effects

    Adverse effects (≥5%): nausea, increased ALT concentrations, increased AST concentrations.

    What other drugs will affect Remdesivir (Systemic)

    In vitro, remdesivir is a substrate of CYP3A4, P-glycoprotein (P-gp), and organic anion transporting polypeptide 1B1 (OATP1B1); the predominant circulating metabolite (GS-441524) is a substrate for OATP1B1 and OATP1B3.

    Remdesivir inhibits CYP3A4, OATP1B1, OATP1B3, and multidrug and toxin extrusion transporter (MATE) 1 in vitro.

    Clinical relevance of in vitro interaction assessments not established.

    Drug-drug interaction trials not conducted in humans.

    Specific Drugs

    Drug

    Interaction

    Comments

    Chloroquine and hydroxychloroquine

    In vitro evidence that antiviral activity of remdesivir is antagonized by chloroquine and hydroxychloroquine in dose-dependent manner; in vitro evidence that increasing concentrations reduce formation of active remdesivir metabolite (GS-443902)

    Concomitant use not recommended

    Dexamethasone

    Minimal or no reduction in remdesivir exposure expected

    Influenza antivirals (Baloxavir, oseltamivir)

    Clinically important interactions not expected

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