REMDESIVIR injection REMDESIVIR injection, powder, lyophilized, for solution

remdesivir by

Drug Labeling and Warnings

remdesivir by is a Prescription medication manufactured, distributed, or labeled by Gilead Sciences, Inc.. Drug facts, warnings, and ingredients follow.

Drug Details [pdf]

  • SPL UNCLASSIFIED SECTION


    FULL EUA PRESCRIBING INFORMATION

    FULL EUA PRESCRIBING INFORMATION:8 ADVERSE REACTIONS AND MEDICATION
    CONTENTS*   ERRORS REPORTING REQUIREMENTS AND
    1 AUTHORIZED USE   INSTRUCTIONS
    2 DOSAGE AND ADMINISTRATION9 OTHER REPORTING REQUIREMENTS
        2.1 Important Testing Prior to and During
    10 DRUG INTERACTIONS
        Treatment and Route of Administration11 USE IN SPECIFIC POPULATIONS
        2.2 Recommended Dosage in Adult Patients    11.1 Pregnancy
        2.3 Recommended Dosage in Pediatric Patients    11.2 Nursing Mothers
        2.4 Pregnancy    11.3 Pediatric Use
        2.5 Renal Impairment    11.4 Geriatric Use
        2.6 Hepatic Impairment    11.5 Renal Impairment
        2.7 Dose Preparation and Administration, Adults    11.6 Hepatic Impairment
              and Pediatric Patients Weighing 40 kg and12 OVERDOSAGE
              Higher13 PRODUCT DESCRIPTION
        2.8 Dose Preparation and Administration, Pediatric    13.1 Physical Appearance
              Patients Weighing 3.5 kg to Less Than 40 kg    13.2 Inactive Ingredients
        2.9 Storage of Prepared Dosages14 CLINICAL PHARMACOLOGY
    3 DOSAGE FORMS AND STRENGTHS    14.1 Mechanism of Action
    4 CONTRAINDICATIONS    14.2 Pharmacokinetics
    5 WARNINGS AND PRECAUTIONS15 MICROBIOLOGY/RESISTANCE INFORMATION
        5.1 Hypersensitivity Including Infusion-Related and
        Anaphylactic Reactions
    16 NONCLINICAL TOXICOLOGY
    17 ANIMAL PHARMACOLOGIC AND EFFICACY
        5.2 Increased Risk of Transaminase Elevations     DATA
        5.3 Risk of Reduced Antiviral Activity When18 CLINICAL TRIAL RESULTS AND SUPPORTING
        Coadministered with Chloroquine or
         DATA FOR EUA
        Hydroxychloroquine19 HOW SUPPLIED/STORAGE AND HANDLING
    6 OVERALL SAFETY SUMMARY20 PATIENT COUNSELING INFORMATION
        6.1 Clinical Trials Experience21 CONTACT INFORMATION
        6.2 Hepatic Adverse Reactions*Sections or subsections omitted from the full
    7 PATIENT MONITORING RECOMMENDATIONSprescribing information are not listed.
  • 1. AUTHORIZED USE

    Veklury (remdesivir) is authorized for use under an EUA for treatment of patients hospitalized with suspected or laboratory confirmed SARS-CoV-2 infection and severe disease. Severe disease is defined as patients with an oxygen saturation (SpO2) ≤94% on room air or requiring supplemental oxygen or requiring mechanical ventilation or requiring extracorporeal membrane oxygenation (ECMO). Specifically, Veklury is only authorized for hospitalized adult and pediatric patients for whom use of an intravenous (IV) agent is clinically appropriate.

  • 2. DOSAGE AND ADMINISTRATION

    2.1 Important Testing Prior to and During Treatment and Route of Administration

    2.2 Recommended Dosage in Adult Patients

    • The recommended dosage in adults is a single loading dose of Veklury 200 mg on Day 1 followed by once-daily maintenance doses of Veklury 100 mg from Day 2 via IV infusion.
    • For patients requiring invasive mechanical ventilation and/or ECMO, total treatment duration is 10 days.
    • For patients not requiring invasive mechanical ventilation and/or ECMO, total treatment duration is 5 days. 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).
    • Administer Veklury via IV infusion in a total volume of up to 250 mL 0.9% sodium chloride over 30 to 120 minutes [see Dosage and Administration (2.7)].

    2.3 Recommended Dosage in Pediatric Patients

    For pediatric patients weighing 3.5 kg to less than 40 kg, the dose should be calculated using the mg/kg dose according to the patient's weight [see Dosage and Administration (2.8), Use in Specific Populations (11.3)]:

    • For pediatric patients weighing 3.5 kg to less than 40 kg, use Veklury (remdesivir) for injection, 100 mg, lyophilized powder only. Do not use Veklury injection, 100 mg/20 mL (5 mg/mL), for pediatric patients weighing 3.5 kg to less than 40 kg due to the higher amount of SBECD present and resulting higher tonicity of the solution concentrate compared to the lyophilized formulation.
    • Refer to Table 1 below for recommended dosage form and dosage in pediatric patients according to weight.
    Table 1: Recommended Dosage Form and Dosage in Pediatric Patients
    Body weightRecommended dosage formLoading dose
    (on Day 1)
    Maintenance dose
    (from Day 2)
    3.5 kg to less than 40 kgVeklury (remdesivir) Lyophilized Powder for Injection Only5 mg/kg2.5 mg/kg
    40 kg and higherVeklury (remdesivir) Lyophilized Powder for Injection
    or
    Veklury (remdesivir) Injection
    200 mg100 mg
    • For pediatric patients requiring invasive mechanical ventilation and/or ECMO, total treatment duration is 10 days.
    • For pediatric patients not requiring invasive mechanical ventilation and/or ECMO, total treatment duration Is 5 days. 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).

    2.4 Pregnancy

    Veklury (remdesivir) should be used during pregnancy only if the potential benefit justifies the potential risk for the mother and the fetus.

    2.5 Renal Impairment

    Adult and pediatric patients (greater than 28 days old) must have an eGFR determined and full-term neonates (at least 7 days to less than or equal to 28 days old) must have serum creatinine determined before dosing and daily while receiving Veklury [see Use in Specific Populations (11.5)].

    •   Adults
      • eGFR, Male: (140 – age in years) × (weight in kg) / 72 × (serum creatinine in mg/dL);
      • eGFR, Female: (140 – age in years) × (weight in kg) × 0.85 / 72 × (serum creatinine in mg/dL)

    •   Pediatric patients (greater than 28 days old to less than 1 year of age)
      • eGFR: 0.45 × (height in cm) / serum creatinine in mg/dL

    •   Pediatric patients (at least 1 year of age to less than 18 years of age)
      • eGFR = 0.413 × (height or length)/Scr) if height/length is expressed in centimeters
        OR
        41.3 × (height or length)/Scr) if height/length is expressed in meters

    Because the excipient SBECD is renally cleared and accumulates in patients with decreased renal function, administration of drugs formulated with SBECD (such as Veklury) is not recommended in adults and pediatric patients (greater than 28 days old) with eGFR less than 30 mL/min or in full-term neonates (at least 7 days and less than or equal to 28 days old) with serum creatinine greater than or equal to 1 mg/dL unless the potential benefit outweighs the potential risk.

    2.6 Hepatic Impairment

    It is not known if dosage adjustment is needed in patients with hepatic impairment, and Veklury should only be used in patients with hepatic impairment if the potential benefit outweighs the potential risk [see Warnings and Precautions (5.2), Use in Specific Populations (11.6)].

    Hepatic laboratory testing should be performed in all patients prior to starting Veklury and daily while receiving Veklury.

    2.7 Dose Preparation and Administration, Adults and Pediatric Patients Weighing 40 kg and Higher

    Adults and pediatric patients weighing 40 kg and higher can use Veklury for injection, 100 mg, lyophilized powder and Veklury injection, 100 mg/20 mL (5 mg/mL), solution. See below for different preparation and administration instructions for the two dosage formulations.

    Veklury (remdesivir) for Injection, 100 mg, Lyophilized Powder

    Reconstitution Instructions

    Remove the required number of single-dose vial(s) from storage. For each vial:

    • Aseptically reconstitute Veklury lyophilized powder by addition of 19 mL of Sterile Water for Injection using a suitably sized syringe and needle per vial.
    • Discard the vial if a vacuum does not pull the Sterile Water for Injection into the vial.
    • Immediately shake the vial for 30 seconds.
    • Allow the contents of the vial to settle for 2 to 3 minutes. A clear solution should result.
    • If the contents of the vial are not completely dissolved, shake the vial again for 30 seconds and allow the contents to settle for 2 to 3 minutes. Repeat this procedure as necessary until the contents of the vial are completely dissolved.
    • Following reconstitution, each vial contains 100 mg/20 mL (5 mg/mL) of remdesivir solution.
    • Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
    • After reconstitution, the total storage time before administration should not exceed 4 hours at room temperature or 24 hours at refrigerated temperature (2°C to 8°C [36°F to 46°F]).

    Dilution Instructions

    Care should be taken during admixture to prevent inadvertent microbial contamination. As there is no preservative or bacteriostatic agent present in this product, aseptic technique must be used in preparation of the final parenteral solution. It is always recommended to administer IV medication immediately after preparation when possible.

    • The reconstituted Veklury lyophilized powder for injection, containing 100 mg/20 mL remdesivir solution, should be further diluted in 100 mL or 250 mL 0.9% sodium chloride infusion bags.
    • Using Table 2, determine the volume of 0.9% sodium chloride to withdraw from the infusion bag.
    Table 2: Recommended Dilution Instructions Using Reconstituted Veklury (remdesivir) for Injection Lyophilized Powder in Adults and Pediatric Patients Weighing 40 kg and Higher
    Veklury dose0.9% sodium chloride infusion bag volume to be usedVolume to be withdrawn and discarded from 0.9% sodium chloride infusion bagRequired volume of reconstituted Veklury for injection
    200 mg
    (2 vials)
    250 mL40 mL40 mL (2 × 20 mL)
    100 mL40 mL40 mL (2 × 20 mL)
    100 mg
    (1 vial)
    250 mL20 mL20 mL
    100 mL20 mL20 mL
    • Withdraw and discard the required volume of 0.9% sodium chloride from the bag per Table 2 using an appropriately sized syringe and needle.
    • Withdraw the required volume of reconstituted Veklury for injection from the Veklury vial using an appropriately sized syringe per Table 2. Discard any unused portion remaining in the Veklury vial.
    • Transfer the required volume of reconstituted Veklury for injection to the selected infusion bag.
    • Gently invert the bag 20 times to mix the solution in the bag. Do not shake.
    • The prepared diluted solution is stable for 4 hours at room temperature (20°C to 25°C [68°F to 77°F]) or 24 hours in the refrigerator at 2°C to 8°C (36°F to 46°F).

    Administration Instructions

    The prepared diluted solution should not be administered simultaneously with any other IV medication. The compatibility of Veklury injection with IV solutions and medications other than 0.9% sodium chloride is not known.

    Administer the diluted solution with the infusion rate described in Table 3.

    Table 3: Recommended Rate of Infusion — Diluted Veklury (remdesivir) for Injection Lyophilized Powder in Adults and Pediatric Patients Weighing 40 kg and Higher
    Infusion bag volumeInfusion timeRate of infusion
    250 mL30 min8.33 mL/min
    60 min4.17 mL/min
    120 min2.08 mL/min
    100 mL30 min3.33 mL/min
    60 min1.67 mL/min
    120 min0.83 mL/min

    Veklury (remdesivir) Injection, 100 mg/20 mL (5 mg/mL), Solution

    Dilution Instructions

    Care should be taken during admixture to prevent inadvertent microbial contamination. As there is no preservative or bacteriostatic agent present in this product, aseptic technique must be used in preparation of the final parenteral solution. It is always recommended to administer IV medication immediately after preparation when possible.

    • Remove the required number of single-dose vial(s) from storage. Each vial contains 100 mg of remdesivir. For each vial:
      • Equilibrate to room temperature (20°C to 25°C [68°F to 77°F]). Sealed vials can be stored up to 12 hours at room temperature prior to dilution.
      • Inspect the vial to ensure the container closure is free from defects and the solution is free of particulate matter.
    • Using Table 4, determine the volume of 0.9% sodium chloride to withdraw from the infusion bag.
    Table 4: Recommended Dilution Instructions— Veklury (remdesivir) Solution in Adults and Pediatric Patients Weighing 40 kg and Higher
    Veklury dose0.9% sodium chloride infusion bag volume to be usedVolume to be withdrawn and discarded from 0.9% sodium chloride infusion bagRequired volume of Veklury injection solution
    200 mg
    (2 vials)
    250 mL40 mL40 mL (2 × 20 mL)
    100 mg
    (1 vial)
    20 mL20 mL
    • Withdraw and discard the required volume of 0.9% sodium chloride from the bag per Table 4 using an appropriately sized syringe and needle.
    • Withdraw the required volume of Veklury injection solution from the Veklury vial using an appropriately sized syringe per Table 4.
      • Pull the syringe plunger rod back to fill the syringe with approximately 10 mL of air.
      • Inject the air into the Veklury injection vial above the level of the solution.
      • Invert the vial and withdraw the required volume of Veklury injection solution into the syringe. The last 5 mL of solution requires more force to withdraw.
    • Discard any unused solution remaining in the Veklury vial.
    • Transfer the required volume of Veklury injection solution to the infusion bag.
    • Gently invert the bag 20 times to mix the solution in the bag. Do not shake.
    • The prepared diluted solution is stable for 4 hours at room temperature (20°C to 25°C [68°F to 77°F]) or 24 hours in the refrigerator at 2°C to 8°C (36°F to 46°F).

    Administration Instructions

    The prepared diluted solution should not be administered simultaneously with any other medication. The compatibility of Veklury injection with IV solutions and medications other than 0.9% sodium chloride is not known.

    Administer the diluted solution with the infusion rate described in Table 5.

    Table 5: Recommended Rate of Infusion—Diluted Veklury (remdesivir) Solution in Adults and Pediatric Patients Weighing 40 kg and Higher
    Infusion bag volumeInfusion timeRate of infusion
    250 mL30 min8.33 mL/min
    60 min4.17 mL/min
    120 min2.08 mL/min

    2.8 Dose Preparation and Administration, Pediatric Patients Weighing 3.5 kg to Less Than 40 kg

    For pediatric patients weighing 3.5 kg to less than 40 kg, use Veklury (remdesivir) for injection, 100 mg, lyophilized powder only. Veklury injection, 100 mg/20 mL (5 mg/mL), should not be used for pediatric patients weighing 3.5 kg to less than 40 kg due to the higher amount of SBECD present and resulting higher tonicity of the solution concentrate compared to the lyophilized formulation.

    Veklury (remdesivir) for Injection, 100 mg, Lyophilized Powder

    Reconstitution Instructions

    Remove the required number of single-dose vial(s) from storage. For each vial:

    • Aseptically reconstitute Veklury lyophilized powder by addition of 19 mL of Sterile Water for Injection using a suitably sized syringe and needle per vial.
      • Discard the vial if a vacuum does not pull the Sterile Water for Injection into the vial.
    • Immediately shake the vial for 30 seconds.
    • Allow the contents of the vial to settle for 2 to 3 minutes. A clear solution should result.
    • If the contents of the vial are not completely dissolved, shake the vial again for 30 seconds and allow the contents to settle for 2 to 3 minutes. Repeat this procedure as necessary until the contents of the vial are completely dissolved.
    • Following reconstitution, each vial contains 100 mg/20 mL (5 mg/mL) of remdesivir solution.
    • Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
    • After reconstitution, the total storage time before administration should not exceed 4 hours at room temperature or 24 hours at refrigerated temperature (2°C to 8°C [36°F to 46°F]).

    Dilution Instructions

    • Care should be taken during admixture to prevent inadvertent microbial contamination. As there is no preservative or bacteriostatic agent present in this product, aseptic technique must be used in preparation of the final parenteral solution. It is always recommended to administer IV medication immediately after preparation when possible. Following reconstitution as instructed above, each vial will contain a 100 mg/20 mL (5 mg/mL) remdesivir concentrated solution. For pediatric patients weighing 3.5 kg to less than 40 kg, the 100 mg/20 mL (5 mg/mL) remdesivir concentrate should be further diluted to a fixed concentration of 1.25 mg/mL using 0.9% sodium chloride.
    • The total required infusion volume of the 1.25 mg/mL remdesivir solution for infusion is calculated from the pediatric weight-based dosing regimens of 5 mg/kg for the Loading Dose and 2.5 mg/kg for each Maintenance Dose.
    • Small 0.9% sodium chloride infusion bags (e.g., 25, 50, or 100 mL) or an appropriately sized syringe should be used for pediatric dosing. The recommended dose is administered via IV infusion in a total volume dependent on the dose to yield the target remdesivir concentration of 1.25 mg/mL.
    • A syringe may be used for delivering volumes less than 50 mL.

    Infusion with IV Bag

    • Prepare an IV bag of 0.9% sodium chloride with volume equal to the total infusion volume minus the volume of reconstituted remdesivir solution that will be diluted to achieve a 1.25 mg/mL solution.
    • Withdraw the required volume of reconstituted solution containing remdesivir for injection into an appropriately sized syringe.
    • Transfer the required volume of reconstituted remdesivir for injection to the 0.9% sodium chloride infusion bag.
    • Gently invert the bag 20 times to mix the solution in the bag. Do not shake.

    Infusion with Syringe

    • Select an appropriately sized syringe equal to or larger than the calculated total infusion volume of 1.25 mg/mL remdesivir solution needed.
    • Withdraw the required volume of 100 mg/20 mL (5 mg/mL) reconstituted remdesivir solution from the vial into the syringe followed by the required volume of 0.9% sodium chloride needed to achieve a 1.25 mg/mL remdesivir solution.
    • Mix the syringe by inversion 20 times.
    • The prepared diluted solution is stable for 4 hours at room temperature (20°C to 25°C [68°F to 77°F]) or 24 hours in the refrigerator at 2°C to 8°C (36°F to 46°F) (including any time before dilution into intravenous infusion fluids).

    Administration Instructions

    The prepared diluted solution should not be administered simultaneously with any other medication. The compatibility of Veklury (remdesivir) injection with IV solutions and medications other than 0.9% sodium chloride is not known.

    Administer the diluted solution with the infusion rate described in Table 6.

    Table 6: Recommended Rate of Infusion—Diluted Veklury (remdesivir) for Injection Lyophilized Powder for Pediatric Patients Weighing 3.5 kg to Less Than 40 kg
    Infusion bag volumeInfusion timeRate of infusion*
  • * Note: Rate of infusion may be adjusted based on total volume to be infused.
  • 100 mL30 min3.33 mL/min
    60 min1.67 mL/min
    120 min0.83 mL/min
    50 mL30 min1.67 mL/min
    60 min0.83 mL/min
    120 min0.42 mL/min
    25 mL30 min0.83 mL/min
    60 min0.42 mL/min
    120 min0.21 mL/min

    2.9 Storage of Prepared Dosages

    Lyophilized Powder

    After reconstitution, vials can be stored up to 4 hours at room temperature (20°C to 25°C [68°F to 77°F]) prior to administration or 24 hours at refrigerated temperature (2°C to 8°C [36°F to 46°F]). Dilute within the same day as administration.

    Injection Solution

    Prior to dilution, equilibrate Veklury injection to room temperature (20°C to 25°C [68°F to 77°F]). Sealed vials can be stored up to 12 hours at room temperature prior to dilution.

    Diluted Infusion Solution

    Store diluted Veklury solution for infusion 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]).

    IMPORTANT:

    This product contains no preservative. Any unused portion of a single-dose Veklury vial should be discarded after a diluted solution is prepared. Maintain adequate records showing receipt, use, and disposition of Veklury. For unused intact vials, maintain adequate records showing disposition of Veklury; do not discard unused intact vials.

  • 3. DOSAGE FORMS AND STRENGTHS

    • Veklury (remdesivir) for injection, 100 mg: Each single-dose vial of Veklury for injection,100 mg, contains a sterile, preservative-free white to off-white to yellow lyophilized powder that is to be reconstituted with 19 mL of Sterile Water for Injection and further diluted into 0.9% sodium chloride infusion bag prior to administration by intravenous infusion. Following reconstitution, each vial contains 100 mg/20 mL (5 mg/mL) remdesivir reconcentrated solution.
    • Veklury (remdesivir) injection, 100 mg/20 mL (5 mg/mL): Each single-dose vial of Veklury injection contains 100 mg/20 mL (5 mg/mL) of remdesivir as a clear, colorless to yellow, aqueous-based concentrated solution that is to be diluted into 0.9% sodium chloride infusion bag prior to administration by intravenous infusion.
  • 4. CONTRAINDICATIONS

    Veklury is contraindicated in patients with known hypersensitivity to any ingredient of Veklury [see Product Description (13)].

  • 5. WARNINGS AND PRECAUTIONS

    There are limited clinical data available for Veklury. Serious and unexpected adverse events may occur that have not been previously reported with Veklury use.

    5.1 Hypersensitivity Including Infusion-Related and Anaphylactic Reactions

    Hypersensitivity reactions including infusion-related and anaphylactic reactions have been observed during and following administration of Veklury. Signs and symptoms may include hypotension, tachycardia, bradycardia, dyspnea, wheezing, angioedema, rash, nausea, vomiting, diaphoresis, and shivering. Slower infusion rates, with a maximum infusion time of up to 120 minutes, can be considered to potentially prevent these signs and symptoms. If signs and symptoms of a clinically significant hypersensitivity reaction occur, immediately discontinue administration of Veklury and initiate appropriate treatment. The use of Veklury is contraindicated in patients with known hypersensitivity to Veklury [see Contraindications (4)].

    5.2 Increased Risk of Transaminase Elevations

    Transaminase elevations have been observed in healthy volunteers who received 200 mg of Veklury followed by 100 mg doses for 5–10 days. Transaminase elevations have also been reported in patients with COVID-19 who received Veklury in clinical trials. As transaminase elevations have been reported as a component of COVID-19, including in patients receiving placebo in clinical trials of Veklury, discerning the contribution of Veklury to transaminase elevations in this patient population is challenging.

    Hepatic laboratory testing should be performed in all patients prior to starting Veklury and daily while receiving Veklury.

    • Veklury should not be initiated in patients with ALT greater than or equal to 5 times the upper limit of normal at baseline.
    • Veklury should be discontinued in patients who develop:
      • ALT greater than or equal to 5 times the upper limit of normal during treatment with Veklury. Veklury may be restarted when ALT is less than 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.

    5.3 Risk of Reduced Antiviral Activity When Coadministered with Chloroquine or Hydroxychloroquine

    Coadministration of Veklury and chloroquine phosphate or hydroxychloroquine sulfate is not recommended based on in vitro data demonstrating an antagonistic effect of chloroquine on the intracellular metabolic activation and antiviral activity of Veklury [see Drug Interactions (10), Microbiology/Resistance Information (15)].

  • 6. OVERALL SAFETY SUMMARY

    Completion of FDA MedWatch Form to report all medication errors and adverse events occurring during Veklury (remdesivir) treatment is mandatory. Please see the ADVERSE REACTIONS AND MEDICATION ERRORS REPORTING REQUIREMENTS AND INSTRUCTIONS section below for details on FDA MedWatch reporting.

    In healthy subjects and hospitalized patients with PCR-confirmed SARS-CoV-2 infection, graded elevations in ALT and AST have been observed with a loading dose of Veklury 200 mg administered intravenously on Day 1 followed by 100 mg administered intravenously once daily for up to 9 days. The mechanism of these elevations is unknown.

    Patients should have appropriate clinical and laboratory monitoring to aid in early detection of any potential adverse events. The decision to continue or discontinue Veklury after development of an adverse event should be made based on the clinical risk benefit assessment for the individual.

    6.1 Clinical Trials Experience

    Clinical Studies in Healthy Adults

    Veklury was evaluated in four Phase 1 studies in 138 healthy adult volunteers (Studies GS-US-399-1812, GS-US-399-1954, GS-US-399-4231, and GS-US-399-5505). In these studies, transient graded elevations in ALT and AST were observed at repeated once-daily doses of Veklury.

    NIAID ACTT-1 Trial

    In a randomized, double-blind, placebo-controlled clinical trial (ACTT-1) of Veklury in 1,063 hospitalized subjects with COVID-19 treated with Veklury (n=541) or placebo (n=522) for 10 days, serious adverse events (SAEs) were reported in 21% and 27% of subjects, respectively, and Grade ≥3 non-serious adverse events were reported in 29% and 33% of subjects, respectively. The most common SAE was respiratory failure reported in 5% of subjects treated with Veklury and 8% of subjects treated with placebo. The most common Grade ≥3 non-serious adverse events in the Veklury treatment arm are shown in Table 7.

    Table 7: Most Common Grade ≥3 Non-Serious Adverse Events in Subjects Receiving Veklury (remdesivir)—NIAID ACTT-1 Trial
    n (%)Veklury
    N=538
    Placebo
    N=521
    Anemia or decreased hemoglobin43 (8%)47 (9%)
    Acute kidney injury, decreased eGFR or creatinine renal clearance, or increased blood creatinine40 (7%)38 (7%)
    Pyrexia27 (5%)17 (3%)
    Hyperglycemia or increased blood glucose22 (4%)17 (3%)
    Increased transaminases, including ALT and/or AST22 (4%)31 (6%)

    Study GS-US-540-5773

    In a randomized, open-label clinical trial (Study GS-US-540-5773) of Veklury in 397 hospitalized subjects with severe COVID-19 treated with Veklury for 5 (n=200) or 10 days (n=197), adverse events were reported in 70% and 74% of subjects, respectively, SAEs were reported in 21% and 35% of subjects, respectively, and Grade ≥3 adverse events were reported in 30% and 43% of subjects, respectively. The most common adverse events were nausea (10% in the 5-day group vs 9% in the 10-day group), acute respiratory failure (6% vs 11%), ALT increased (6% vs 8%), and constipation (7% in both groups). Nine (4%) subjects in the 5-day group and 20 (10%) subjects in the 10-day group discontinued treatment due to an adverse event. All-cause mortality at Day 28 was 10% vs 13% in the 5- and 10-day treatment groups, respectively.

    6.2 Hepatic Adverse Reactions

    Clinical Trials Experience

    Experience in Healthy Volunteers

    Grade 1 and 2 transaminase elevations were observed in healthy volunteers in Study GS-US-399-5505 (200 mg followed by 100 mg dosing for 5–10 days) and Study GS-US-399-1954 (150 mg daily for 7 or 14 days), which resolved after discontinuation of Veklury (remdesivir).

    Experience in Subjects with COVID-19

    NIAID ACTT-1 trial

    Grade ≥3 non-serious adverse events of increased aminotransferase levels including ALT, AST, or both were reported in 4% of subjects receiving Veklury compared with 6% receiving placebo.

    Study GS-US-540-5773

    Grade ≥3 hepatic laboratory abnormalities reported in subjects treated with Veklury for 5 (n=200) or 10 days (n=197) are shown in Table 8.

    Table 8: Hepatic Laboratory Abnormalities—Study GS-US-540-5773
    n/N (%)Veklury (remdesivir) for 5 DaysVeklury (remdesivir) for 10 DaysTotal
    ALT IncreasedGrade 38/194 (4%)11/191 (6%)19/385 (5%)
    Grade 44/194 (2%)5/191 (3%)9/385 (2%)
    AST IncreasedGrade 311/194 (6%)7/190 (4%)18/384 (5%)
    Grade 43/194 (2%)4/190 (2%)7/384 (2%)
    Total Bilirubin IncreasedGrade 31/193 (1%)3/190 (2%)4/383 (1%)
    Grade 401/190 (1%)1/383 (<1%)

    Compassionate Use Experience

    In the compassionate use program in patients with severe or critical illness with COVID-19, liver function test abnormalities were reported in 12% (19/163) of patients. Time to onset from first dose ranged from 1–16 days. Four of these patients discontinued Veklury treatment with elevated transaminases occurring on Day 5 of Veklury treatment as per protocol.

    Seven cases of serious liver-related laboratory abnormality were identified. There was one SAE of blood bilirubin increased in a critically ill patient with septic shock and multiorgan failure. None of the other cases had reported adverse events suggestive of hyperbilirubinemia or symptoms of hepatitis.

  • 7. PATIENT MONITORING RECOMMENDATIONS

    Given the limited experience with Veklury (remdesivir) at the recommended dose and duration, patients should have appropriate clinical and laboratory monitoring to aid in early detection of any potential adverse events while receiving Veklury [see Dosage and Administration (2.1)]. Additionally, completion of FDA MedWatch Form to report all medication errors and serious adverse events is mandatory.

    For mandatory reporting requirements, please see "MANDATORY REQUIREMENTS FOR VEKLURY (remdesivir) ADMINISTRATION UNDER EMERGENCY USE AUTHORIZATION" above.

  • 8. ADVERSE REACTIONS AND MEDICATION ERRORS REPORTING REQUIREMENTS AND INSTRUCTIONS

    See Overall Safety Summary (Section 6) for additional information.

    The prescribing health care provider and/or the provider's designee are/is responsible for the mandatory reporting of all medication errors and the following selected adverse events occurring during Veklury (remdesivir) use and considered to be potentially attributable to Veklury. These adverse events must be reported within 7 calendar days from the onset of the event:

    • Deaths
    • Serious Adverse Events
      Serious Adverse Events are defined as:
      • death;
      • a life-threatening adverse event;
      • inpatient hospitalization or prolongation of existing hospitalization;
      • a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions;
      • a congenital anomaly/birth defect;
      • a medical or surgical intervention to prevent death, a life-threatening event, hospitalization, disability, or congenital anomaly.

    If a serious and unexpected adverse event occurs and appears to be associated with the use of Veklury, the prescribing health care provider and/or the provider's designee should complete and submit a MedWatch form to FDA using one of the following methods:

    • Complete and submit the report online: www.fda.gov/medwatch/report.htm, or
    • Use a postage-paid Form FDA 3500 (available at http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM163919.pdf) and returning by mail (MedWatch, 5600 Fishers Lane, Rockville, MD 20852-9787), or by fax (1-800-FDA-0178), or
    • Call 1-800-FDA-1088 to request a reporting form

    IMPORTANT: When reporting adverse events or medication errors to MedWatch, please complete the entire form with detailed information. It is important that the information reported to FDA be as detailed and complete as possible. Information to include:

    • Patient demographics (e.g., patient initials, date of birth)
    • Pertinent medical history
    • Pertinent details regarding admission and course of illness
    • Concomitant medications
    • Timing of adverse event(s) in relationship to administration of Veklury
    • Pertinent laboratory and virology information
    • Outcome of the event and any additional follow-up information if it is available at the time of the MedWatch report. Subsequent reporting of follow-up information should be completed if additional details become available.

    The following steps are highlighted to provide the necessary information for safety tracking:

    1. In section A, box 1, provide the patient's initials in the Patient Identifier
    2. In section A, box 2, provide the patient's date of birth
    3. In section B, box 5, description of the event:
      • a. Write "Veklury (remdesivir) EUA" as the first line
      • b. Provide a detailed report of medication error and/or adverse event. It is important to provide detailed information regarding the patient and adverse event/medication error for ongoing safety evaluation of this unapproved drug. Please see information to include listed above.
    4. In section G, box 1, name and address:
      • a. Provide the name and contact information of the prescribing health care provider or institutional designee who is responsible for the report.
      • b. Provide the address of the treating institution (NOT the health care provider's office address).
  • 9. OTHER REPORTING REQUIREMENTS

    In addition please provide a copy of all FDA MedWatch forms to:

    Gilead Pharmacovigilance and Epidemiology

    Fax: 1-650-522-5477

    E-mail: Safety_fc@gilead.com

  • 10. DRUG INTERACTIONS

    Drug-drug interaction trials of Veklury (remdesivir) and other concomitant medications have not been conducted in humans. Due to antagonism observed in vitro, concomitant use of Veklury with chloroquine phosphate or hydroxychloroquine sulfate is not recommended [see Warnings and Precautions (5.3), Microbiology/resistance information (15)].

    In vitro, remdesivir is a substrate for drug metabolizing enzymes CYP2C8, CYP2D6, and CYP3A4, and is a substrate for Organic Anion Transporting Polypeptides 1B1 (OATP1B1) and P-glycoprotein (P-gp) 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.

  • 11. USE IN SPECIFIC POPULATIONS

    11.1 Pregnancy

    Risk Summary

    No adequate and well-controlled studies of Veklury (remdesivir) use in pregnant women have been conducted. Veklury should be used during pregnancy only if the potential benefit justifies the potential risk for the mother and the fetus.

    In nonclinical reproductive toxicity studies, remdesivir demonstrated no adverse effect on embryofetal development when administered to pregnant animals at systemic exposures (AUC) 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 (RHD) (see Data).

    Animal Data

    Remdesivir was administered via intravenous injection to pregnant rats and rabbits (up to 20 mg/kg/day) on Gestation Days 6 through 17, and 7 through 20, respectively, and also to rats from Gestation Day 6 to Lactation/Post-partum Day 20. No adverse effects on embryo-fetal (rats and rabbits) or pre/postnatal (rats) development were observed in rats and rabbits at nontoxic doses in pregnant animals. During organogenesis, exposures to the predominant circulating metabolite (GS-441524) were 4 (rats and rabbits) times higher than the exposure in humans at the RHD. In a pre/postnatal development study, exposures to the predominant circulating metabolite of remdesivir (GS-441524) were similar to the human exposures at the RHD.

    11.2 Nursing Mothers

    Risk Summary

    There is no information regarding the presence of remdesivir in human milk, the effects on the breastfed infant, or the effects on milk production. In animal studies, remdesivir and metabolites have been detected in the nursing pups of mothers given remdesivir, likely due to the presence of remdesivir in milk. Because of the potential for viral transmission to SARS-CoV-2-negative infants and adverse reactions from the drug in breastfeeding infants, the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Veklury and any potential adverse effects on the breastfed child from Veklury or from the underlying maternal condition.

    Animal Data

    Remdesivir and its metabolites were detected in the plasma of nursing rat pups, likely due to the presence of remdesivir and/or its metabolites in milk, following daily intravenous administration of remdesivir to pregnant mothers from Gestation Day 6 to Lactation Day 20. Exposures in nursing pups were approximately 1% that of maternal exposure on lactation day 10.

    11.3 Pediatric Use

    The safety, effectiveness, or pharmacokinetics of Veklury for treatment of COVID-19 have not been assessed in pediatric patients. Physiologically-based pharmacokinetics (PBPK) modeling of pharmacokinetic data from healthy adults was used to derive pediatric doses. Pediatric doses are expected to result in comparable steady-state exposures of remdesivir and metabolites as observed in healthy adults following administration of the recommended dosage regimen.

    For pediatric patients with weighing 3.5 kg to less than 40 kg, use Veklury (remdesivir) for injection, 100 mg, lyophilized powder only. Veklury injection, 100 mg/20 mL (5 mg/mL), should not be used for pediatric patients weighing 3.5 kg to less than 40 kg due to the higher amount of SBECD present and resulting higher tonicity of the solution concentrate compared to the lyophilized formulation [see Dosage and Administration (2.3 and 2.8)].

    Pediatric patients (older than 28 days) must have eGFR determined and full-term neonates (at least 7 days to less than or equal to 28 days) must have serum creatinine determined before dosing and daily while receiving Veklury. Pediatric patients should be monitored for renal function and consideration given for stopping therapy in the setting of substantial decline [see Dosage and Administration (2.1, 2.5)].

    Because the excipient SBECD is renally cleared and accumulates in patients with decreased renal function, administration of drugs formulated with SBECD (such as Veklury) is not recommended in adults and pediatric patients (older than 28 days old) with eGFR less than 30 mL/min or in full-term neonates (at least 7 days and less than or equal to 28 days old) with serum creatinine greater than or equal to 1 mg/dL unless the potential benefit outweighs the potential risk.

    11.4 Geriatric Use

    The pharmacokinetics of Veklury have not been evaluated in patients >65 years of age. In general, appropriate caution should be exercised in the administration of Veklury and monitoring of elderly patients, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

    11.5 Renal Impairment

    Patients with eGFR greater than or equal to 30 mL/min have received Veklury for treatment of COVID-19 with no dose adjustment. The safety and efficacy of Veklury have not been assessed in patients with severe renal impairment or ESRD. The pharmacokinetics of Veklury have not been evaluated in patients with renal impairment. Veklury is not recommended in adults and pediatric patients (at least 28 days old) with eGFR less than 30 mL/min or in full-term neonates (at least 7 days and less than or equal to 28 days old) with serum creatinine greater than or equal to 1 mg/dL unless the potential benefit outweighs the potential risk [see Dosage and Administration (2.1)].

    Adult and pediatric patients (greater than 28 days old) must have eGFR determined and full-term neonates (at least 7 days to less than or equal to 28 days old) must have serum creatinine determined before dosing and daily while receiving Veklury.

    11.6 Hepatic Impairment

    The pharmacokinetics of Veklury have not been evaluated in patients with hepatic impairment. It is not known if dosage adjustment is needed in patients with hepatic impairment, and Veklury should only be used in patients with hepatic impairment if the potential benefit outweighs the potential risk [see Warnings and Precautions (5.2)].

    Hepatic laboratory testing should be performed in all patients prior to starting Veklury and daily while receiving Veklury [see Dosage and Administration (2.1)].

  • 12. OVERDOSAGE

    There is no human experience of acute overdosage with Veklury (remdesivir). Treatment of overdose with Veklury should consist of general supportive measures including monitoring of vital signs and observation of the clinical status of the patient. There is no specific antidote for overdose with Veklury.

  • 13. PRODUCT DESCRIPTION

    Remdesivir is a nucleoside ribonucleic acid (RNA) polymerase inhibitor.

    The chemical name for remdesivir is 2-ethylbutyl N-{(S)-[2-C-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-2,5-anhydro-d-altrononitril-6-O-yl]phenoxyphosphoryl}-L-alaninate. It has a molecular formula of C27H35N6O8P and a molecular weight of 602.6 g/mol. Remdesivir has the following structural formula:

    Chemical Structure

    13.1 Physical Appearance

    Lyophilized Powder

    Veklury (remdesivir) for injection, 100 mg, is a sterile, preservative-free lyophilized powder that is to be reconstituted with 19 mL of Sterile Water for Injection and further diluted into 0.9% sodium chloride infusion bag prior to administration by intravenous infusion. Veklury for injection, 100 mg, is supplied in a single-dose clear glass vial.

    The appearance of the lyophilized powder is white to off-white to yellow.

    Injection Solution

    Veklury (remdesivir) injection, 100 mg/20 mL (5 mg/mL), is a sterile, preservative-free, clear, colorless to yellow, aqueous-based concentrated solution that is to be diluted into 0.9% sodium chloride infusion bag prior to administration by intravenous infusion. Veklury injection, 100 mg/20 mL (5 mg/mL), is supplied in a single-dose clear glass vial.

    13.2 Inactive Ingredients

    The inactive ingredients are sulfobutylether-β-cyclodextrin sodium salt (SBECD), Water for Injection, USP, and may include hydrochloric acid and/or sodium hydroxide for pH adjustment. Veklury for injection, 100 mg, contains 3 g SBECD, and Veklury injection, 100 mg/20 mL (5 mg/mL), contains 6 g SBECD.

  • 14. CLINICAL PHARMACOLOGY

    14.1 Mechanism of Action

    Remdesivir is an 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 has been demonstrated in multiple cell types. Remdesivir triphosphate 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.

    14.2 Pharmacokinetics

    The pharmacokinetics (PK) of Veklury (remdesivir) have been evaluated in adults in several Phase 1 trials.

    • The pharmacokinetics of remdesivir and metabolites have not been in evaluated in patients with COVID-19.
    • Following single-dose, 2-hour IV administration of Veklury solution formulation at doses ranging from 3 to 225 mg, remdesivir exhibited a linear PK profile.
    • Following single-dose, 2-hour IV administration of Veklury at doses of 75 and 150 mg, both the lyophilized and solution formulations provided comparable PK parameters (AUCinf, AUClast, and Cmax), indicating similar formulation performance.
    • Veklury 75 mg lyophilized formulation administered IV over 30 minutes provided similar peripheral blood mononuclear cell (PBMC) exposure of the active triphosphate metabolite GS-443902 as Veklury 150 mg lyophilized formulation administered IV over 2 hours.
    • Following a single 150 mg intravenous dose of [14C]-remdesivir, mean total recovery of the dose was >92%, consisting of approximately 74% and 18% recovered in urine and feces, respectively. The majority of remdesivir dose recovered in urine was metabolite GS-441524 (49%), while 10% was recovered as remdesivir.

    Specific Populations

    Sex, Race and Age

    Pharmacokinetic differences based on sex, race, and age have not been evaluated.

    Pediatric Patients

    The pharmacokinetics of Veklury in pediatric patients has not been evaluated.

    PBPK modeling of pharmacokinetic data from healthy adults was used to derive pediatric doses. PBPK modeling incorporated in vitro data for remdesivir and other similar compounds along with age-dependent changes in physiology (e.g., organ volume/function, blood flow), metabolism, distribution, and elimination of remdesivir. Pediatric doses are expected to result in comparable steady-state exposures of remdesivir and metabolites as observed in healthy adults following administration of the recommended dosage regimen.

    Renal Impairment

    Because the excipient SBECD is renally cleared and accumulates in patients with decreased renal function, administration of drugs formulated with SBECD (such as Veklury) is not recommended in adult and pediatric patients (greater than 28 days old) with eGFR less than 30 mL/min or in full-term neonates (at least 7 days and less than or equal to 28 days old) with serum creatinine greater than or equal to 1 mg/dL unless the potential benefit outweighs the potential risk.

  • 15. MICROBIOLOGY/RESISTANCE INFORMATION

    Antiviral Activity

    Remdesivir exhibited cell culture antiviral activity against a clinical isolate of SARS-CoV-2 in primary human airway epithelial (HAE) cells with a 50% effective concentration (EC50) of 9.9 nM after 48 hours of treatment. The EC50 values of remdesivir against SARS-CoV-2 in Vero cells was 137 nM at 24 hours and 750 nM at 48 hours post-treatment. The antiviral activity of remdesivir was antagonized by chloroquine phosphate in a dose-dependent manner when the two drugs were co-incubated at clinically relevant concentrations in HEp-2 cells infected with respiratory syncytial virus (RSV). Higher remdesivir EC50 values were observed with increasing concentrations of chloroquine phosphate. Increasing concentrations of chloroquine phosphate reduced formation of remdesivir triphosphate in normal human bronchial epithelial cells.

    Resistance

    No clinical data are available on the development of SARS-CoV-2 resistance to remdesivir. The cell culture development of SARS-CoV-2 resistance to remdesivir has not been assessed to date.

    Cell culture resistance profiling of remdesivir using the rodent CoV murine hepatitis virus identified 2 substitutions (F476L and V553L) in the viral RNA-dependent RNA polymerase at residues conserved across CoVs that conferred a 5.6-fold reduced susceptibility to remdesivir. The mutant viruses showed reduced viral fitness in cell culture and introduction of the corresponding substitutions (F480L and V557L) into SARS-CoV resulted in 6-fold reduced susceptibility to remdesivir in cell culture and attenuated SARS-CoV pathogenesis in a mouse model.

  • 16. NONCLINICAL TOXICOLOGY

    Carcinogenesis

    Given the short-term administration of Veklury (remdesivir) for the treatment of COVID-19, long-term animal studies to evaluate the carcinogenic potential of remdesivir are not required.

    Mutagenesis

    Remdesivir was not genotoxic in a battery of assays, including bacterial mutagenicity, chromosome aberration using human peripheral blood lymphocytes, and in vivo rat micronucleus assays.

    Impairment of Fertility

    Nonclinical toxicity studies in rats demonstrated no adverse effect on male fertility at exposures of the predominant circulating metabolite (GS-441524) approximately 2 times the exposure in humans at the RHD.

    Reproductive toxicity, including decreases in corpora lutea, numbers of implantation sites, and viable embryos, was seen when remdesivir was administered intravenous daily at a systemically toxic dose (10 mg/kg) in female rats 14 days prior to mating and during conception; exposures of the predominant circulating metabolite (GS-441524) were 1.3 times the exposure in humans at the RHD.

    Animal Toxicology and/or Pharmacology

    Intravenous administration (slow bolus) of remdesivir to male rhesus monkeys at dosage levels of 5, 10, and 20 mg/kg/day for 7 days resulted, at all dose levels, in increased mean urea nitrogen and increased mean creatinine, renal tubular atrophy, and basophilia and casts.

    Intravenous administration (slow bolus) of remdesivir to rats at dosage levels of ≥3 mg/kg/day for up to 4 weeks resulted in findings indicative of kidney injury and/or dysfunction.

  • 17. ANIMAL PHARMACOLOGIC AND EFFICACY DATA

    It is unknown, at present, how the observed antiviral activity of remdesivir in animal models of SARS-CoV-2 infection will translate into clinical efficacy in patients with symptomatic disease. Key attributes of the remdesivir nonclinical profile supporting its development for the treatment of COVID-19 are provided below:

    • Remdesivir showed cell culture antiviral activity against a clinical isolate of SARS-CoV-2 in primary HAE cells (EC50 value= 9.9 nM). The EC50 values of remdesivir against SARS-CoV-2 in Vero cells has been reported to be 137 nM at 24 hours and 750 nM at 48 hours post-treatment.
    • Remdesivir showed antiviral activity in SARS-CoV-2-infected rhesus monkeys. Administration of remdesivir at 10/5 mg/kg (10 mg/kg first dose, followed by 5 mg/kg once daily thereafter) using IV bolus injection initiated 12 hours post-inoculation with SARS-CoV-2 resulted in a reduction in clinical signs of respiratory disease, lung pathology and gross lung lesions, and lung viral RNA levels compared with vehicle-treated animals.
  • 18. CLINICAL TRIAL RESULTS AND SUPPORTING DATA FOR EUA

    Veklury (remdesivir) is an unapproved antiviral drug with available data from two randomized clinical trials in patients with COVID-19.

    Clinical Trials in Subjects with COVID-19

    NIAID ACTT-1 Trial in Subjects with Mild/Moderate and Severe COVID-19

    A randomized, double-blind, placebo-controlled clinical trial evaluated Veklury 200 mg once daily for 1 day followed by Veklury 100 mg once daily for 9 days (for a total of up to 10 days of intravenously administered therapy) in hospitalized adult subjects with COVID-19 with evidence of lower respiratory tract involvement. The trial enrolled 1,063 subjects: 120 [11.3%] subjects with mild/moderate disease and 943 [88.7%] subjects with severe disease. A total of 272 subjects (25.6%) (n=125 received Veklury) were on mechanical ventilation/ECMO. Subjects were randomized in a 1:1 manner, stratified by disease severity at enrollment, to receive Veklury (n=541) or placebo (n=522), plus standard of care. The primary clinical endpoint was time to recovery within 28 days after randomization, defined as either discharged from the hospital or hospitalized but not requiring supplemental oxygen and no longer requiring ongoing medical care. In a preliminary analysis of the primary endpoint performed after 607 recoveries were attained (n=1,059; 538 Veklury, 521 placebo), the median time to recovery was 11 days in the Veklury group compared to 15 days in the placebo group (recovery rate ratio 1.32; 95% CI 1.12 to 1.55, p<0.001); 14-day mortality was 7.1% for the Veklury group versus 11.9% for the placebo group (hazard ratio 0.70 [95% CI 0.47, 1.04], p=0.07). Among subjects with mild/moderate disease at enrollment (n=119), the median time to recovery was 5 days in both the Veklury and placebo groups (recovery rate ratio 1.09; [95% CI 0.73 to 1.62]). Among subjects with severe disease at enrollment (n=940), the median time to recovery was 12 days in the Veklury group compared to 18 days in the placebo group (recovery rate ratio, 1.37; [95% CI, 1.15 to 1.63]; p<0.001; n=940) and 14-day mortality was 7.7% and 13%, respectively (hazard ratio, 0.71; [95% CI, 0.48 to 1.05]).

    Overall, the odds of improvement in the ordinal scale were higher in the Veklury group at Day 15 when compared to the placebo group (odds ratio, 1.50; [95% CI, 1.18 to 1.91], p=0.001; n=844).

    Study GS-US-540-5773 in Subjects with Severe COVID-19

    A randomized, open-label multi-center clinical trial (Study GS-US-540-5773) of hospitalized subjects at least 12 years of age with confirmed SARS-CoV-2 infection, oxygen saturation of ≤94% on room air, and radiological evidence of pneumonia compared 200 subjects who received IV Veklury (remdesivir) for 5 days with 197 subjects who received IV Veklury for 10 days. Patients on mechanical ventilation at screening were excluded. All subjects received 200 mg of Veklury on Day 1 and 100 mg once daily on subsequent days, plus standard of care. The primary endpoint was clinical status on Day 14 assessed on a 7-point ordinal scale ranging from hospital discharge to increasing levels of oxygen and ventilatory support to death. After adjusting for between-group differences at baseline, patients receiving a 10-day course of Veklury had similar clinical status at Day 14 as those receiving a 5-day course (odds ratio for improvement: 0.75; [95% CI 0.51 to 1.12]).

    Clinical improvement was defined as an improvement of two or more points from baseline on the 7-point ordinal scale. Subjects achieved clinical recovery if they no longer required oxygen support or were discharged from the hospital. At Day 14, observed rates between the 5- and 10-day treatment groups were 65% vs 54% for clinical improvement, 70% vs 59% for clinical recovery, and 8% vs 11% for mortality.

  • 19. HOW SUPPLIED/STORAGE AND HANDLING

    How Supplied

    Lyophilized Powder

    Veklury (remdesivir) for injection, 100 mg, is supplied as a single-dose vial containing a sterile, preservative-free white to off-white to yellow lyophilized powder that is to be reconstituted with 19 mL of Sterile Water for Injection and further diluted into 0.9% sodium chloride infusion bag prior to administration by intravenous infusion. Following reconstitution, each vial contains 100 mg/20 mL (5 mg/mL) remdesivir reconcentrated solution.

    Discard unused portion.

    The container closure is not made with natural rubber latex.

    Injection Solution

    Veklury (remdesivir) injection is supplied as a single dose vial containing 100 mg/20 mL (5 mg/mL) of remdesivir per vial for dilution into 0.9% sodium chloride infusion bag.

    Discard unused portion.

    The container closure is not made with natural rubber latex.

    Storage and Handling

    Do not reuse or save unused Veklury lyophilized powder, injection solution, or diluted solution for infusion for future use. This product contains no preservative.

    Lyophilized Powder

    Store Veklury for injection, 100 mg, vials below 30°C (below 86°F) until required for use. Do not use after expiration date.

    After reconstitution, vials can be stored up to 4 hours at room temperature (20°C to 25°C [68°F to 77°F]) prior to administration or 24 hours at refrigerated temperature (2°C to 8°C [36°F to 46°F]). Dilute within the same day as administration.

    Injection Solution

    Store Veklury injection, 100 mg/20 mL (5 mg/mL), vials at refrigerated temperature (2°C to 8°C [36°F to 46°F]) until required for use. Do not use after expiration date. Dilute within the same day as administration.

    Prior to dilution, equilibrate Veklury injection to room temperature (20°C to 25°C [68°F to 77°F]). Sealed vials can be stored up to 12 hours at room temperature prior to dilution.

    Diluted Solution for Infusion

    Store diluted Veklury solution for infusion 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]).

  • 20. PATIENT COUNSELING INFORMATION
  • 21. CONTACT INFORMATION

    If you have questions, please contact

    www.askgileadmedical.com

    1-866-633-4474

    © 2020 Gilead Sciences, Inc. All rights reserved.
    Revised: 07/2020

  • PATIENT PACKAGE INSERT


    Fact Sheet for Patients And Parents/Caregivers
    Emergency Use Authorization (EUA) Of Veklury® (remdesivir) For Coronavirus Disease 2019
    (COVID-19)

    You are being given a medicine called Veklury (remdesivir) for the treatment of coronavirus disease 2019 (COVID-19). This Fact Sheet contains information to help you understand the potential risks and potential benefits of taking Veklury, which you have received or may receive.

    There is no U.S. Food and Drug Administration (FDA) approved product available to treat COVID-19. Receiving Veklury may benefit certain people in the hospital with COVID-19. Read this Fact Sheet for information about Veklury. Talk to your healthcare provider if you have questions. It is your choice to receive Veklury or stop it at any time.

    What is COVID-19?

    COVID-19 is caused by a virus called a coronavirus. This type of coronavirus has not been seen before. You can get COVID-19 through contact with another person who has the virus.

    COVID-19 illnesses have ranged from very mild (including some with no reported symptoms) to severe, including illness resulting in death. While information so far suggests that most COVID-19 illness is mild, serious illness can happen and may cause some of your other medical conditions to become worse. Older people and people of all ages with severe, long-lasting (chronic) medical conditions like heart disease, lung disease, and diabetes, for example, seem to be at higher risk of being hospitalized for COVID-19.

    What are the symptoms of COVID-19?

    The symptoms of COVID-19 are fever, cough, and shortness of breath, which may appear 2 to 14 days after exposure. Serious illness including breathing problems can occur and may cause your other medical conditions to become worse.

    What is Veklury (remdesivir)?

    Veklury is an investigational antiviral medicine used for the treatment of certain people in the hospital with COVID-19. Veklury is investigational because it is still being studied. There is limited information known about the safety and effectiveness of using Veklury to treat people in the hospital with COVID-19. Veklury was shown in a clinical trial to shorten the time to recovery in some people. There are no medicines approved by the FDA as safe and effective to treat people in the hospital who have COVID-19. Therefore, the FDA has authorized the emergency use of Veklury for the treatment of COVID-19 under an Emergency Use Authorization (EUA). For more information on EUA, see the "What is an Emergency Use Authorization (EUA)?" section at the end of this Fact Sheet.

    What should I tell my healthcare provider before I receive Veklury (remdesivir)?

    Tell your healthcare provider about all of your medical conditions, including if you:

    • Have any allergies
    • Have kidney or liver problems
    • Are pregnant or plan to become pregnant
    • Are breastfeeding or plan to breastfeed
    • Have any serious illnesses
    • Are taking any medicines (prescription, over-the-counter, vitamins, or herbal products). Veklury may affect the way other medicines work, and other medicines may affect how Veklury works.
      • Especially tell your healthcare provider if you are taking the medicines chloroquine phosphate or hydroxychloroquine sulfate.

    How will I receive Veklury (remdesivir)?

    Veklury is given to you through a vein (intravenous or IV) one time each day for up to 10 days depending on what your healthcare provider thinks is best for you. Veklury may help decrease the amount of the coronavirus in your body. This may help you to get better faster.

    What are the important possible side effects of Veklury (remdesivir)?

    Possible side effects of Veklury are:

    • Allergic reactions. Veklury can cause allergic reactions, including serious reactions, during and after infusion. Tell your healthcare provider or nurse, or get medical help right away if you get any of the following signs and symptoms of allergic reactions: low blood pressure, changes in your heartbeat, shortness of breath, wheezing, swelling of your lips, face, or throat, rash, nausea, vomiting, sweating, or shivering.
    • Increases in levels of liver enzymes. Increases in levels of liver enzymes have been seen in people who have received Veklury, which may be a sign of inflammation or damage to cells in the liver. Your healthcare provider will do blood tests to check your liver before you receive Veklury and daily while receiving Veklury.

    These are not all the possible side effects of Veklury. Veklury is still being studied so it is possible that all of the risks are not known at this time.

    Not a lot of people have taken Veklury. Serious and unexpected side effects may happen. The side effects of getting any medicine by vein may include brief pain, bleeding, bruising of the skin, soreness, swelling, and possible infection at the injection site.

    What other treatment choices are there?

    Like Veklury, FDA may allow for the emergency use of other medicines to treat people in the hospital with COVID-19. Go to https://www.covid19treatmentguidelines.nih.gov/ for information on the emergency use of other medicines that are not approved by FDA to treat people in the hospital with COVID-19. Your healthcare provider may talk with you about clinical trials you may be eligible for.

    It is your choice to be treated or not to be treated with Veklury. Should you decide not to receive it or stop it at any time, it will not change your standard medical care.

    What if I am pregnant or breastfeeding?

    There is limited experience giving Veklury to pregnant women or breastfeeding mothers. For a mother and unborn baby, the benefit of receiving Veklury may be greater than the risk from the treatment. If you are pregnant or breastfeeding, discuss your options and specific situation with your healthcare provider.

    How do I report side effects with Veklury (remdesivir)?

    Tell your healthcare provider right away if you have any side effect that bothers you or does not go away.

    Report side effects to FDA MedWatch at www.fda.gov/medwatch or call 1-800-FDA-1088.

    How can I learn more?

    • Ask your healthcare provider.
    • Visit https://www.covid19treatmentguidelines.nih.gov/
    • Contact your local or state public health department.

    What is an Emergency Use Authorization (EUA)?

    The United States FDA has made Veklury available under an emergency access mechanism called an EUA. The EUA is supported by a Secretary of Health and Human Service (HHS) declaration that circumstances exist to justify the emergency use of drugs and biological products during the COVID-19 pandemic.

    Veklury has not undergone the same type of review as an FDA-approved or cleared product. FDA may issue an EUA when certain criteria are met, which includes that there are no adequate, approved, available alternatives. In addition, the FDA decision is based on the totality of scientific evidence available showing that it is reasonable to believe that the product meets certain criteria for safety, performance, and labeling and may be effective in treatment of patients during the COVID-19 pandemic. All of these criteria must be met to allow for the product to be used in the treatment of patients during the COVID-19 pandemic.

    The EUA for Veklury (remdesivir) is in effect for the duration of the COVID-19 declaration justifying emergency use of these products, unless terminated or revoked (after which the products may no longer be used).

  • SPL UNCLASSIFIED SECTION

    © 2020 Gilead Sciences, Inc. All rights reserved.
    Revised: 07/2020

  • PRINCIPAL DISPLAY PANEL - 20 mL Vial Label

    Veklury®
    (remdesivir) injection
    100 mg/20 mL (5 mg/mL)

    For Intravenous Infusion Only
    Single-Dose Vial: Discard Unused Portion

    Must be diluted prior to use

    For use under Emergency
    Use Authorization (EUA)

    90286903

    Rx only

    PRINCIPAL DISPLAY PANEL - 20 mL Vial Label
  • PRINCIPAL DISPLAY PANEL - 20 mL Vial Carton

    61958-2902-1
    Rx only

    Veklury®
    (remdesivir) injection
    100 mg/20 mL
    (5 mg/mL)

    For Intravenous Infusion Only
    Single-Dose Vial: Discard
    Unused Portion

    Must be diluted prior to use

    For use under Emergency
    Use Authorization (EUA)

    GILEAD

    PRINCIPAL DISPLAY PANEL - 20 mL Vial Carton
  • PRINCIPAL DISPLAY PANEL - 100 mg Vial Label

    Veklury®
    (remdesivir) for injection
    100 mg/vial

    For Intravenous Infusion Only
    Single-Dose Vial: Discard
    Unused Portion

    Must be reconstituted and
    further diluted prior to use
    For use under Emergency
    Use Authorization (EUA)

    90287203

    Rx only

    PRINCIPAL DISPLAY PANEL - 100 mg Vial Label
  • PRINCIPAL DISPLAY PANEL - 100 mg Vial Carton

    61958-2901-1
    Rx only

    Veklury®
    (remdesivir) for injection
    100 mg/vial

    For Intravenous Infusion Only
    Single-Dose Vial: Discard
    Unused Portion

    Must be reconstituted and
    further diluted prior to use

    For use under Emergency
    Use Authorization (EUA)

    GILEAD

    PRINCIPAL DISPLAY PANEL - 100 mg Vial Carton
  • INGREDIENTS AND APPEARANCE
    REMDESIVIR 
    remdesivir injection
    Product Information
    Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC: 61958-2902
    Route of AdministrationINTRAVENOUS
    Active Ingredient/Active Moiety
    Ingredient NameBasis of StrengthStrength
    REMDESIVIR (UNII: 3QKI37EEHE) (REMDESIVIR - UNII:3QKI37EEHE) REMDESIVIR5 mg  in 1 mL
    Inactive Ingredients
    Ingredient NameStrength
    BETADEX SULFOBUTYL ETHER SODIUM (UNII: 2PP9364507)  
    WATER (UNII: 059QF0KO0R)  
    HYDROCHLORIC ACID (UNII: QTT17582CB)  
    SODIUM HYDROXIDE (UNII: 55X04QC32I)  
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    1NDC: 61958-2902-11 in 1 CARTON05/01/2020
    120 mL in 1 VIAL, SINGLE-DOSE; Type 0: Not a Combination Product
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    UNAPPROVED DRUG OTHER05/01/2020
    REMDESIVIR 
    remdesivir injection, powder, lyophilized, for solution
    Product Information
    Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC: 61958-2901
    Route of AdministrationINTRAVENOUS
    Active Ingredient/Active Moiety
    Ingredient NameBasis of StrengthStrength
    REMDESIVIR (UNII: 3QKI37EEHE) (REMDESIVIR - UNII:3QKI37EEHE) REMDESIVIR100 mg
    Inactive Ingredients
    Ingredient NameStrength
    BETADEX SULFOBUTYL ETHER SODIUM (UNII: 2PP9364507)  
    WATER (UNII: 059QF0KO0R)  
    HYDROCHLORIC ACID (UNII: QTT17582CB)  
    SODIUM HYDROXIDE (UNII: 55X04QC32I)  
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    1NDC: 61958-2901-11 in 1 CARTON05/01/2020
    11 in 1 VIAL, SINGLE-DOSE; Type 0: Not a Combination Product
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    UNAPPROVED DRUG OTHER05/01/2020
    Labeler - Gilead Sciences, Inc. (185049848)

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