Additions and/or revisions underlined:

…

Clinical Trials in Pediatric Subjects

Study GS-US-540-5823 was a Phase 2/3, single-arm, open-label clinical trial in hospitalized subjects from birth to <18 years of age and weighing at least 1.5 kg with mild, moderate, and severe COVID- 19 treated with weight-based VEKLURY (n=58) for up to 10 days [see Clinical Studies (14.6)]:

• Cohorts 1, 8: Subjects greater than or equal to 12 years and weighing greater than or equal to 40 kg (n=12) and subjects <12 years and weighing greater than or equal to 40 kg (n=5): Received 200 mg on Day 1 and 100 mg once daily on subsequent days.

• Cohorts 2-4: Subjects greater than or equal to 28 days and weighing greater than or equal to 20 to <40 kg (n=12); subjects greater than or equal to 28 days and weighing greater than or equal to 12 to <20 kg (n=12); and subjects greater than or equal to 28 days and weighing greater than or equal to 3 to <12 kg (n=12): Received 5 mg/kg on Day 1 and 2.5 mg/kg once daily on subsequent days.

• Cohort 5: Subjects 14 to <28 days old, gestational age (GA) >37 weeks, and weighing greater than or equal to 2.5 kg (n=3): Received 5 mg/kg on Day 1 and 2.5 mg/kg once daily on subsequent days.

• Cohorts 6-7: Subjects <14 days old, GA >37 weeks, and weighing greater than or equal to 2.5 kg at birth (n=1); and subjects <56 days old, GA less than or equal to 37 weeks, and weighing greater than or equal to 1.5 kg at birth (n=1): Received 2.5 mg/kg on Day 1 and 1.25 mg/kg once daily on subsequent days.

  The adverse reactions observed were consistent with those observed in clinical trials of VEKLURY in adults.

  Infants, children, and adolescents; Cohorts 1-4, 8: Adverse reactions (all grades) were reported in 8 (15%) subjects.

  …

  Neonates and infants; Cohorts 5-7: Laboratory abnormalities (Grades 3-4) were reported in 3/5 subjects: APTT increased (2/5); direct bilirubin increased (1/5); creatinine increased (1/5); prothrombin time increased (1/5); prothrombin/INR increased (1/5); and potassium increased (1/5).

  …

Additions and/or revisions underlined:

The safety and effectiveness of VEKLURY for the treatment of COVID-19 have been established in pediatric patients from birth to less than 18 years of age and weighing at least 1.5 kg, who are:

• Hospitalized, or

• Not hospitalized and have mild-to-moderate COVID-19, and are at high risk for progression to severe COVID-19, including hospitalization or death.

  Use in this age group is supported by the following:

• Trials in adults [see Clinical Studies (14.1, 14.2, 14.3, 14.4, 14.5)]

• An open-label trial (Study 5823) in 58 hospitalized pediatric subjects [see Adverse Reactions (6.1), Clinical Pharmacology (12.3), and Clinical Studies (14.6)].

  Use of VEKLURY in pediatric patients from birth to less than 18 years of age and weighing at least1.5 kg is supported by Study 5823 where 58 hospitalized pediatric subjects were treated with weight- based VEKLURY for up to 10 days in the following cohorts:

• Cohorts 1-4, 8; infants, children, and adolescents: Subjects greater than or equal to 12 years and weighing greater than or equal to 40 kg (n=12); subjects <12 years and weighing greater than or equal to 40 kg (n=5); subjects greater than or equal to 28 days and weighing greater than or equal to 20 to <40 kg (n=12); subjects greater than or equal to 28 days and weighing greater than or equal to 12 to <20 kg (n=12); and subjects greater than or equal to 28 days and weighing greater than or equal to 3 to <12 kg (n=12);

• Cohorts 5-7; neonates and infants: Subjects 14 to <28 days old, GA >37 weeks, and weighing

  Greater than or equal to 2.5 kg (n=3); subjects <14 days old, GA >37 weeks, and weighing greater than or equal to 2.5 kg at birth (n=1); and subjects <56 days old, GA less than or equal to 37 weeks, and weighing greater than or equal to 1.5 kg at birth (n=1).

  …

  The safety and effectiveness of VEKLURY have not been established in pediatric patients weighing less than 1.5 kg.

Additions and/or revisions underlined:

What is VEKLURY?

VEKLURY is a prescription medicine used for the treatment of coronavirus disease 2019 (COVID-19) in adults and children weighing at least 3 pounds (1.5 kg) who are:

• Hospitalized, or

• Not hospitalized and have mild-to-moderate COVID-19 and are at high risk for progression to severe COVID-19, including hospitalization or death.

  It is not known if VEKLURY is safe and effective in children weighing less than 3 pounds (1.5 kg).

  …

Extensive changes; please refer to label

• a randomized, double-blind, placebo-controlled trial (Study 5912) in adults [see Adverse Reactions (6.1) and Clinical Pharmacology (12.3)].

• an open-label, parallel-group, single-dose trial in subjects with normal renal function and renal impairment (Study 9015) [see Clinical Pharmacology (12.3)].

The pharmacokinetics and safety of VEKLURY in patients with COVID-19 and renal impairment, including those on dialysis, were evaluated in 163 subjects in a randomized, double-blind, placebo- controlled trial, Study GS-US-540-5912 [see Adverse Reactions (6.1) and Clinical Pharmacology (12.3)].

Study GS-US-540-5912 evaluated VEKLURY 200 mg once daily for 1 day followed by VEKLURY 100 mg once daily for 4 days (for a total of up to 5 days of intravenously administered therapy) in 243 hospitalized adult subjects with confirmed COVID-19 and renal impairment. The trial included 90 subjects (37%) with AKI (defined as a 50% increase in serum creatinine within a 48-hour period that was sustained for ?6 hours despite supportive care), 64 subjects (26%) with CKD (eGFR <30 mL/minute/1.73m2), and 89 subjects (37%) with ESRD (eGFR <15 mL/minute/1.73m2) requiring hemodialysis. Subjects were randomized in a 2:1 manner, stratified by ESRD, high-flow oxygen requirement, and region (US vs ex-US) to receive VEKLURY (n=163) or placebo (n=80), plus standard of care.

At baseline, mean age was 69 years (with 62% of subjects aged 65 or older); 57% of subjects were male, 67% were White, 26% were Black, and 3% were Asian. The most common baseline risk factors were hypertension (89%), diabetes mellitus (79%), and cardiovascular or cerebrovascular disease (51%); the distribution of risk factors was similar between the two treatment groups. A total of 45 subjects (19%) were on high-flow oxygen, 144 (59%) were on low-flow oxygen, and 54 (22%) were on room air at baseline; no subjects were on invasive mechanical ventilation (IMV). A total of 182 subjects (75%) were not on renal replacement therapy, and 31 subjects (13%) had received a COVID-19 vaccine.

The safety results in subjects with COVID-19 and renal impairment, including those on dialysis, were consistent with those observed in clinical trials of VEKLURY in adults [see Adverse Reactions (6.1)]. Study GS-US-540-5912 closed prematurely due to feasibility issues and was underpowered to assess for efficacy because of lower than expected enrollment.

The pharmacokinetics and safety of VEKLURY in subjects with normal renal function and renal impairment, including those on dialysis, were evaluated in 75 subjects (43 subjects with renal impairment plus 32 matched control subjects with normal renal function) in an open-label, parallel- group, single-dose trial, Study GS-US-540-9015 [see Clinical Pharmacology (12.3)].

In studies GS-US-540-5912 and GS-US-540-9015, exposures of GS-441524 and GS-704277, the metabolites of remdesivir, and SBECD are increased in subjects with mild to severe renal impairment, including those requiring dialysis, relative to subjects with normal renal function [see Clinical Pharmacology (12.3)].

No dosage adjustment of VEKLURY is recommended for patients with any degree of renal impairment, including those on dialysis [see Dosage and Administration (2.2, 2.4), Use in Specific Populations (8.4)].

8.7 Hepatic Impairment

Additions and/or revisions underlined

No dosage adjustment of VEKLURY is recommended for patients with mild, moderate, or severe hepatic impairment (Child-Pugh Class A, B, or C) [see Clinical Pharmacology (12.3)].

Perform hepatic laboratory testing in all patients before starting VEKLURY and while receiving VEKLURY as clinically appropriate [see Dosage and Administration (2.2) and Warnings and Precautions (5.2)].

6.1 Clinical Trials Experience

Extensive changes; please refer to label

• an open-label, parallel-group, single-dose trial in subjects with normal renal function and renal impairment (Study 9015) [see Clinical Pharmacology (12.3)].

The pharmacokinetics and safety of VEKLURY in patients with COVID-19 and renal impairment, including those on dialysis, were evaluated in 163 subjects in a randomized, double-blind, placebo- controlled trial, Study GS-US-540-5912 [see Adverse Reactions (6.1) and Clinical Pharmacology (12.3)].

Study GS-US-540-5912 evaluated VEKLURY 200 mg once daily for 1 day followed by VEKLURY 100 mg once daily for 4 days (for a total of up to 5 days of intravenously administered therapy) in 243 hospitalized adult subjects with confirmed COVID-19 and renal impairment. The trial included 90 subjects (37%) with AKI (defined as a 50% increase in serum creatinine within a 48-hour period that was sustained for ?6 hours despite supportive care), 64 subjects (26%) with CKD (eGFR <30 mL/minute/1.73m2), and 89 subjects (37%) with ESRD (eGFR <15 mL/minute/1.73m2) requiring hemodialysis. Subjects were randomized in a 2:1 manner, stratified by ESRD, high-flow oxygen requirement, and region (US vs ex-US) to receive VEKLURY (n=163) or placebo (n=80), plus standard of care.

At baseline, mean age was 69 years (with 62% of subjects aged 65 or older); 57% of subjects were male, 67% were White, 26% were Black, and 3% were Asian. The most common baseline risk factors were hypertension (89%), diabetes mellitus (79%), and cardiovascular or cerebrovascular disease (51%); the distribution of risk factors was similar between the two treatment groups. A total of 45 subjects (19%) were on high-flow oxygen, 144 (59%) were on low-flow oxygen, and 54 (22%) were on room air at baseline; no subjects were on invasive mechanical ventilation (IMV). A total of 182 subjects (75%) were not on renal replacement therapy, and 31 subjects (13%) had received a COVID-19 vaccine.

The safety results in subjects with COVID-19 and renal impairment, including those on dialysis, were consistent with those observed in clinical trials of VEKLURY in adults [see Adverse Reactions (6.1)]. Study GS-US-540-5912 closed prematurely due to feasibility issues and was underpowered to assess for efficacy because of lower than expected enrollment.

The pharmacokinetics and safety of VEKLURY in subjects with normal renal function and renal impairment, including those on dialysis, were evaluated in 75 subjects (43 subjects with renal impairment plus 32 matched control subjects with normal renal function) in an open-label, parallel- group, single-dose trial, Study GS-US-540-9015 [see Clinical Pharmacology (12.3)].

In studies GS-US-540-5912 and GS-US-540-9015, exposures of GS-441524 and GS-704277, the metabolites of remdesivir, and SBECD are increased in subjects with mild to severe renal impairment, including those requiring dialysis, relative to subjects with normal renal function [see Clinical Pharmacology (12.3)].

No dosage adjustment of VEKLURY is recommended for patients with any degree of renal impairment, including those on dialysis [see Dosage and Administration (2.2, 2.4), Use in Specific Populations (8.4)].

8.1 Pregnancy

Additions and/or revisions underlined:

…

Risk Summary

Risk Summary

Available data from a clinical trial (IMPAACT 2032), published reports, the ongoing COVID-PR pregnancy exposure registry, and compassionate use of remdesivir in pregnant individuals have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes following exposure in the second and third trimester. However, there are insufficient pregnancy data available to evaluate the risk of remdesivir exposure during the first trimester. A study evaluating the pharmacokinetics of remdesivir during pregnancy demonstrated no clinically relevant differences between pregnant and non-pregnant individuals. No dose adjustments are recommended in patients who receive VEKLURY during pregnancy (see Data) and [see Clinical Pharmacology (12.3)].

…

Data

Human Data

A non-randomized, open-label clinical study (IMPAACT 2032) evaluated pharmacokinetics and safety of up to 10 days of treatment with VEKLURY in 25 hospitalized pregnant and 28 hospitalized non- pregnant individuals of childbearing potential. Subjects received VEKLURY 200 mg once daily for 1 day followed by VEKLURY 100 mg once daily on subsequent days via intravenous infusion. Subjects were enrolled prior to their fourth VEKLURY infusion. Assessments occurred at the following intervals: Screening; Pre-infusion (defined as 48 hours prior to start of first infusion); each infusion day; 48 hours after the last infusion; 7 days after the last infusion; 4 weeks after the last infusion.

Assessments also occurred 24 hours post-delivery in subjects who delivered. Treatment with VEKLURY was stopped in subjects who were discharged from the hospital prior to the completion of 10 days of treatment.

Of the 25 pregnant subjects, median age was 33 years (Q1, Q3: 27 years, 37 years); 40% were White, 24% were Black, and 48% were Hispanic or Latino. A total of 9 subjects (36%) were on high- flow oxygen; 12 subjects (48%) were on low-flow oxygen; and 1 subject (4%) was on room air, at baseline. Three subjects (12%) did not have data available on baseline oxygen status. The overall median (Q1, Q3) duration of symptoms prior to hospitalization was 7 (6, 9) days. The overall median (Q1, Q3) duration of symptoms prior to first dose of VEKLURY was 8 (6, 9) days.

Of the 25 pregnant subjects, median gestational age was 28 weeks at baseline (range 22 to 33 weeks) and about half of subjects were in each of the second and third trimester of pregnancy. No clinically relevant differences in the pharmacokinetics of remdesivir or its metabolites (GS-704277 and GS-441524) were observed between pregnant (n=21) and non-pregnant (n=22) individuals [see Clinical Pharmacology (12.3)]. No difference in pharmacokinetics of remdesivir or its metabolites is expected between the first and second/third trimesters. The adverse reactions observed were consistent with those observed in clinical trials of VEKLURY in adults [see Adverse Reactions (6.1)]. There were no adverse reactions in infants born during the study (n=16).

8.2 Lactation

Additions and/or revisions underlined:

Risk Summary

A published case report describes the presence of remdesivir and active metabolite GS-441524 in human milk. Available data (n=11) from pharmacovigilance reports do not indicate adverse effects on breastfed infants from exposure to remdesivir and its metabolite through breastmilk. There are no available data on the effects of remdesivir on milk production.

…

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 rats from Gestation Day 6 to Lactation Day 20. Exposures in nursing pups were approximately 1% that of maternal exposure on Lactation Day 10. The concentration of remdesivir in animal milk does not necessarily predict the concentration of drug in human milk.

Additions and/or revisions underlined:

Before receiving VEKLURY, tell your healthcare provider about all of your medical conditions, including if you:

…

• are pregnant or plan to become pregnant. It is not known if VEKLURY may harm your unborn baby if taken during the first trimester of pregnancy.

…

Additions and/or revisions underlined

…

Remdesivir and its metabolites are in vitro substrates and/or inhibitors of certain drug metabolizing enzymes and transporters. Based on a drug interaction study conducted with VEKLURY, no clinically significant drug interactions are expected with inducers of cytochrome P450 (CYP) 3A4 or inhibitors of Organic Anion Transporting Polypeptides (OATP) 1B1/1B3, and P-glycoprotein (P-gp) [see Clinical Pharmacology (12.3)].

Addotions underlined

…

Clinical Trials in Pediatric Subjects

Study GS-US-540-5823 was a Phase 2/3, single-arm, open-label clinical trial in hospitalized subjects 28 days of age and older and weighing at least 3 kg with mild, moderate, and severe COVID-19 treated with weight-based VEKLURY (n=53) for up to 10 days [see Clinical Studies (14.6)]:

• Subjects greater than or equal to 12 years and weighing greater than or equal to 40 kg (n=12) and subjects <12 years and weighing ?40 kg

  (n=5): Received 200 mg on Day 1 and 100 mg once daily on subsequent days.

• Subjects greater than or equal to 28 days and weighing greater than or equal to 20 to <40 kg (n=12); subjects greater than or equal to 28 days and weighing greater than or equal to 12 to

  <20 kg (n=12); and subjects greater than or equal to 28 days and weighing greater than or equal to 3 to <12 kg (n=12): Received 5 mg/kg on Day 1 and 2.5 mg/kg once daily on subsequent days.

  The adverse reactions observed were consistent with those observed in clinical trials of VEKLURY in adults. Adverse reactions (all grades) were reported in 8 (15%) subjects. The most common adverse reaction occurring in at least 5% of subjects was ALT increased (6%). No subjects experienced serious adverse reactions. Two (4%) subjects permanently discontinued treatment due to adverse reactions (ALT increased [n=1], ALT increased and AST increased and hyperbilirubinemia [n=1]). Laboratory abnormalities (Grades 3-4) occurring in at least 3% of subjects with COVID-19 receiving VEKLURY in Trial 5823 and who had at least one post-baseline value for the specified test were hemoglobin decreased (18%, 9/51), eGFR decreased (18%, 7/40), creatinine increased (10%, 5/52), direct bilirubin increased (9%, 2/23), prothrombin time increased (7%, 3/46), APTT increased (7%, 3/45), lymphocytes decreased (6% 2/33), proteinuria (6%, 2/36), WBC decreased (4%, 2/51), ALT increased (4%, 2/51), glucose increased (4%, 2/52), glycosuria (4%, 2/46), potassium decreased (4%, 2/52).

  …

Additions and revisions underlined

The safety and effectiveness of VEKLURY for the treatment of COVID-19 have been established in pediatric patients 28 days of age and older and weighing at least 3 kg, who are:

• Hospitalized, or

• Not hospitalized and have mild-to-moderate COVID-19, and are at high risk for progression to severe COVID-19, including hospitalization or death.

  Use in this age group is supported by the following:

• trials in adults [see Clinical Studies (14.1, 14.2, 14.3, 14.4, 14.5)]

• an open-label trial (Study 5823) in 53 hospitalized pediatric subjects [see Adverse Reactions (6.1), Clinical Pharmacology (12.3), and Clinical Studies (14.6)].

  Use of VEKLURY in pediatric patients 28 days of age and older and weighing at least 3 kg is supported by Study 5823 where 53 hospitalized pediatric subjects were treated with weight-based VEKLURY for up to 10 days in the following cohorts: subjects greater than or equal to 12 years and weighing greater than or equal to 40 kg (n=12); subjects <12 years and weighing greater than or equal to 40 kg (n=5); subjects greater than or equal to 28 days and weighing greater than or equal to 20 to <40 kg (n=12); subjects greater than or equal to 28 days and weighing greater than or equal to 12 to <20 kg (n=12); and subjects greater than or equal to 28 days and weighing greater than or equal to 3 to <12 kg (n=12). The safety and pharmacokinetic results in pediatric subjects in this group were similar to those in adults [see Adverse Reactions (6.1), Clinical Pharmacology (12.3), Clinical Studies (14.6)].

  Use of VEKLURY in pediatric patients weighing at least 40 kg is further supported by a clinical trial of VEKLURY in non-hospitalized subjects that included 3 pediatric subjects 12 years and older, and by clinical trials in hospitalized subjects that included 30 adult subjects weighing 40 to 50 kg. The safety in this weight group was comparable to adult subjects weighing greater than 50 kg. Thirty-nine pediatric patients 12 years and older and weighing at least 40 kg received VEKLURY in a compassionate use program in hospitalized subjects; the available clinical data from these patients are limited [see Adverse Reactions (6.1) and Clinical Studies (14)].

  All pediatric patients 28 days of age and older and weighing at least 3 kg must have eGFR determined before starting VEKLURY and while receiving VEKLURY as clinically appropriate [see Dosage and Administration (2.2, 2.4), Adverse Reactions (6.1), Use in Specific Populations (8.6)].

  The safety and effectiveness of VEKLURY have not been established in pediatric patients younger than 28 days of age or weighing less than 3 kg.

Additions underlined

What is VEKLURY?

VEKLURY is a prescription medicine used for the treatment of coronavirus disease 2019 (COVID-19) in adults and children 28 days of age and older and weighing at least 7 pounds (3 kg) who are:

• Hospitalized, or

• Not hospitalized and have mild-to-moderate COVID-19, and are at high risk for progression to severe COVID-19, including hospitalization or death.

  It is not known if VEKLURY is safe and effective in children under 28 days of age or weighing less than 7 pounds (3 kg).

  …

Additions and/or revisions underlined

Hypersensitivity reactions, including infusion-related and anaphylactic reactions, have been observed during and following administration of VEKLURY; most occurred within one hour. Signs and symptoms may include hypotension, hypertension, tachycardia, bradycardia, hypoxia, fever, dyspnea, wheezing, angioedema, rash, nausea, 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. Monitor patients during infusion and observe patients for at least one hour after infusion is complete for signs and symptoms of hypersensitivity as clinically appropriate. 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 or any components of the product [see Contraindications (4)].

Additions underlined

…

The safety of VEKLURY is based on data from three Phase 3 studies in 1,313 hospitalized adult subjects with COVID-19, one Phase 3 study in 279 non-hospitalized adult and pediatric subjects (12 years of age and older weighing at least 40 kg) with mild-to-moderate COVID-19, four Phase 1 studies in 131 healthy adults, and from patients with COVID-19 who received VEKLURY under the Emergency Use Authorization or in a compassionate use program.

…

Table 6 Summary of Adverse Reaction Rates in Hospitalized Subjects with Severe COVID- 19 in Study 5773

Table 7 Summary of Adverse Reactiona Rates in Hospitalized Subjects with Moderate COVID-19 in Study 5774

Please refer to label to view Tables 6 and 7

Study GS-US-540-9012 was a randomized, double-blind, placebo-controlled clinical trial in subjects who were non-hospitalized, were symptomatic for COVID-19 for less than or equal to 7 days, had confirmed SARS-CoV- 2 infection, and had at least one risk factor for progression to hospitalization treated with VEKLURY (n=279; 276 adults and 3 pediatric subjects 12 years of age and older weighing at least 40 kg) or placebo (n=283; 278 adults and 5 pediatric subjects 12 years of age and older weighing at least 40 kg) for 3 days. Of the 279 subjects treated with VEKLURY, 227 subjects received at least one dose of VEKLURY at an outpatient facility, 44 subjects received at least one dose of VEKLURY in a home healthcare setting, and 8 subjects received at least one dose of VEKLURY at a skilled nursing facility. Subjects treated with VEKLURY received 200 mg on Day 1 and 100 mg once daily on subsequent days [see Clinical Studies (14.4)]. Adverse reactions (all grades) were reported in 34 (12%) subjects in the VEKLURY group and 25 (9%) subjects in the placebo group. The most common adverse reaction occurring in at least 5% of subjects in the VEKLURY group was nausea (6%). There were no serious adverse reactions or adverse reactions leading to treatment discontinuation in either treatment group. Safety in subjects who received VEKLURY in a home healthcare setting was comparable to that observed in the overall GS-US-540-9012 study population, but these findings are based on limited data.

…

Table 8 Laboratory Abnormalities (Grades 3-4) Reported in greater than or equal to 3% of Hospitalized Subjects with Mild, Moderate, or Severe COVID-19 in NIAID ACTT-1

Table 9 Laboratory Abnormalities (Grades 3-4) Reported in greater than or equal to 3% of Hospitalized Subjects with Severe COVID-19 in Trial 5773

Table 10 Laboratory Abnormalities (Grades 3-4) Reported in greater than or equal to 3% of Hospitalized Subjects with Moderate COVID-19 in Trial 5774

Please refer to label to view tables 8, 9, and 10

The frequencies of laboratory abnormalities (Grades 3-4) occurring in at least 2% of subjects with COVID-19 receiving VEKLURY in Trial GS-US-540-9012 are presented in Table 11.

Table 11 Laboratory Abnormalities (Grades 3-4) Reported in greater than or equal to 2% of Non-Hospitalized Subjects in Trial 9012

Please refer to label to view Table 11

Additions underlined

Pregnancy Exposure Registry

There is a pregnancy exposure registry that monitors pregnancy outcomes in individuals exposed to VEKLURY during pregnancy. Pregnant and recently pregnant individuals can go to https://covid- pr.pregistry.com to enroll or call 1-800-616-3791 to obtain information about the registry.

Risk Summary

…

There are maternal and fetal risks associated with untreated COVID-19 in pregnancy (see Clinical Considerations).

…

Clinical Considerations

Disease-associated maternal and/or embryo-fetal risk

COVID-19 in pregnancy is associated with adverse maternal and fetal outcomes, including preeclampsia, eclampsia, preterm birth, premature rupture of membranes, venous thromboembolic disease, and fetal death.

…

Additions underlined

The safety and effectiveness of VEKLURY for the treatment of COVID-19 have been established in pediatric patients 12 years and older and weighing at least 40 kg, who are:

• Hospitalized, or

• Not hospitalized and have mild-to-moderate COVID-19, and are at high risk for progression to severe COVID-19, including hospitalization or death.

  Use in this age group is based on extrapolation of pediatric efficacy from adequate and well- controlled studies in adults [see Adverse Reactions (6.1), Clinical Pharmacology (12.3), and Clinical Studies (14)].

  Clinical trials of VEKLURY in hospitalized subjects included 30 adult subjects weighing 40 to 50 kg. The safety in this weight group was comparable to adult subjects weighing greater than 50 kg. Thirty- nine pediatric patients 12 years and older and weighing at least 40 kg received VEKLURY in a compassionate use program in hospitalized subjects; the available clinical data from these patients are limited.

  …

Additions underlined

Of the 1,062 hospitalized subjects with SARS-CoV-2 infection randomized in ACTT-1, 36% were 65 years or older. Of the 397 hospitalized subjects with SARS-CoV-2 infection randomized in Study GS- US-540-5773, 42% were 65 years or older. Of the 584 hospitalized subjects with SARS-CoV-2 infection randomized in Study GS-US-540-5774, 27% were 65 years or older. Of the 562 non- hospitalized subjects with SARS-CoV-2 infection randomized in Study GS-US-540-9012, 17% were 65 years or older.

…

Additions underlined

…

Pregnancy Registry

Advise patients that there is a pregnancy registry that monitors pregnancy outcomes in individuals exposed to VEKLURY during pregnancy [see Use in Specific Populations (8.1)].

…

Additions underlined

What is VEKLURY?

VEKLURY is a prescription medicine used for the treatment of coronavirus disease 2019 (COVID-19) in adults and children 12 years of age and older and weighing at least 88 pounds (40 kg) who are:

• Hospitalized, or

• Not hospitalized and have mild-to-moderate COVID-19, and are at high risk for progression to severe COVID-19, including hospitalization or death.

  …

  Before receiving VEKLURY, tell your healthcare provider about all of your medical conditions, including if you:

• have kidney problems

• have liver problems

• are pregnant or plan to become pregnant. It is not known if VEKLURY can harm your unborn baby. Tell your healthcare provider right away if you are or if you become pregnant.

  Pregnancy Registry: There is a pregnancy registry for individuals who receive VEKLURY during pregnancy. The purpose of this registry is to collect information about the health of you and your baby. Talk with your healthcare provider about how you can take part in this registry.

  …

  How will I receive VEKLURY?

• Hospitalized: VEKLURY is given to you through a vein by intravenous (IV) infusion one time each day for up to 10 days. Your healthcare provider will decide how many doses you need.

• Not hospitalized: VEKLURY is given to you through a vein by intravenous (IV) infusion one time each day for 3 days.

  Your healthcare provider will do certain blood tests before starting and during treatment with VEKLURY.

  What are the possible side effects of VEKLURY?

  VEKLURY may cause serious side effects, including:

  Allergic reactions. Allergic reactions can happen during or after infusion with VEKLURY. Your healthcare provider will monitor you for signs and symptoms of allergic reactions during your infusion and for at least 1 hour after your infusion.

  …

(Additions and/or revisions underlined)

Coadministration of VEKLURY and chloroquine phosphate or hydroxychloroquine

sulfate is not recommended based on data from cell culture experiments demonstrating a potential antagonistic effect of chloroquine on the intracellular metabolic activation and antiviral activity of VEKLURY [see Drug Interactions (7) and Microbiology (12.4)].

(Additions and/or revisions underlined)

Due to potential antagonism based on data from cell culture experiments, concomitant use of VEKLURY with chloroquine phosphate or hydroxychloroquine sulfate is not recommended [see Warnings and Precautions (5.3) and Microbiology (12.4)].

Drug-drug interaction trials of VEKLURY and other concomitant medications have not been conducted in humans. Remdesivir and its metabolites are in vitro substrates and/or inhibitors of certain drug metabolizing enzymes and transporters. The clinical relevance of these in vitro assessments has not been established [see Clinical Pharmacology (12.3)].