Dear Healthcare Provider:

Gilead Sciences, Inc., would like to clarify the appropriate use and the variable packaging and labeling of the antiviral VEKLURY® (remdesivir).

Gilead's remdesivir (brand name VEKLURY) was approved by the US Food and Drug Administration (FDA) on January 21, 2022 for adults and pediatric patients (12 years of age and older and weighing at least 40 kg) for the treatment of coronavirus disease 2019 (COVID-19) with positive results of direct severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral testing, 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.

Healthcare providers should administer VEKLURY in these patients per the current US Prescribing Information available at www.gilead.com/science-and-medicine/medicines; please also see Important Safety Information at the end of this letter.

Emergency use of Gilead's remdesivir (brand name VEKLURY) for treatment of COVID-19 in pediatric patients weighing 3.5 kg to less than 40 kg or pediatric patients less than 12 years of age weighing at least 3.5 kg with positive results of direct SARS-CoV-2 viral testing, 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.

On January 21, 2022, FDA revised the Emergency Use Authorization (EUA) for VEKLURY, which now authorizes VEKLURY for use by healthcare providers to treat COVID-19 in pediatric patients weighing 3.5 kg to less than 40 kg or pediatric patients less than 12 years of age weighing at least 3.5 kg with positive results of direct SARS-CoV-2 viral testing, 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. Only Gilead's VEKLURY (remdesivir) for injection (supplied as 100 mg lyophilized powder in vial) is authorized for emergency use under the terms and conditions set forth in the Letter of Authorization for the EUA.

The safety and efficacy of VEKLURY to treat COVID-19 in pediatric patients weighing 3.5 kg to less than 40 kg or pediatric patients less than 12 years of age weighing at least 3.5 kg with positive results of direct SARS-CoV-2 viral testing has not been established, and VEKLURY is not FDA approved for this use. For information about the authorized use of VEKLURY in pediatric patients weighing 3.5 kg to less than 40 kg or pediatric patients less than 12 years of age weighing at least 3.5 kg, including dosing, administration, and preparation instructions, please review the EUA Fact Sheet for Healthcare Providers and FDA Letter of Authorization available at www.gilead.com/remdesivir.

Variations in packaging and labeling of Gilead's remdesivir (brand name VEKLURY)

Gilead's VEKLURY (remdesivir) has been manufactured for use under an EUA, and for commercial use. As such, VEKLURY has different packaging, labeling, and expiration dates depending on the date of manufacture. Packaging and labeling for Gilead's remdesivir EUA use may not necessarily include the brand name, VEKLURY.

To help avoid potential drug shortage, hospitals should continue to use all unexpired, unopened vials of Gilead's remdesivir – whether or not the vial includes the brand name VEKLURY or is labeled for use under EUA. Refer to the attached chart at the end of this letter that outlines what hospitals should do with unexpired, unopened vials of Gilead's remdesivir.

Authentic VEKLURY or remdesivir, manufactured by Gilead Sciences, Inc., will include the GILEAD name and logo on the carton and vial label. All packaging includes the drug name remdesivir. Current packaging variations for the two formulations are described below. Both formulations are for intravenous infusion only.

• VEKLURY® (remdesivir) for injection (supplied as 100 mg lyophilized powder in vial). The lyophilized powder formulation is always supplied with a red cap and the package and labeling may be marked "for use under Emergency Use Authorization (EUA)".
• VEKLURY® (remdesivir) injection (supplied as 100 mg/20 mL [5 mg/mL], solution in vial). The solution formulation is supplied with a blue cap and the package and labeling may be marked "for use under Emergency Use Authorization (EUA)". The solution should only be used in adults and pediatric patients 12 years of age and older and weighing at least 40 kg.

Veklury (remdesivir) injection (solution; left) and Veklury (remdesivir) for injection (lyophilized powder; right) now approved by FDA for use in accordance with the prescribing information (PI).

Veklury (remdesivir) injection (solution; left) and Veklury (remdesivir) for injection (lyophilized powder; right) previously authorized for emergency use.

Reporting Adverse Events and Medication Errors

Healthcare providers should direct questions on VEKLURY packaging or use to Gilead Sciences at 1-866-633-4474 or www.askgileadmedical.com.

Under the Emergency Use Authorization, the prescribing healthcare provider and/or the provider's designee are/is responsible for mandatory reporting of all serious adverse events and medication errors potentially related to VEKLURY treatment within 7 calendar days from the healthcare provider's awareness of the event using FDA Form 3500. Healthcare providers must report all serious adverse events and medication errors to FDA when utilizing VEKLURY under the EUA in accordance with the Healthcare Provider Fact Sheet.

For additional information about VEKLURY, including the full Prescribing Information, please visit www.vekluryhcp.com.

Information and reports of suspicious, counterfeit, or unregistered remdesivir can be submitted to Gilead [email protected] and/or www.fraud.org/fakerx.

____________________
Signatory
Signatory Department

U.S. Indication and Important Safety Information for VEKLURY® (remdesivir)

Indication

VEKLURY is indicated for the treatment of COVID-19 in adults and pediatric patients ≥12 years old and weighing ≥40 kg with positive results of SARS-CoV-2 viral testing, 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.

• VEKLURY is contraindicated in patients with a history of clinically significant hypersensitivity reactions to VEKLURY or any of its components.

Warnings and precautions

• Hypersensitivity, including infusion-related and anaphylactic reactions: Hypersensitivity, including infusion-related and anaphylactic reactions, has been observed during and following administration of VEKLURY; most occurred within 1 hour. Monitor patients during infusion and observe for at least 1 hour after infusion is complete for signs and symptoms of hypersensitivity as clinically appropriate. Symptoms may include hypotension, hypertension, tachycardia, bradycardia, hypoxia, fever, dyspnea, wheezing, angioedema, rash, nausea, diaphoresis, and shivering. Slower infusion rates (maximum infusion time of up to120 minutes) can potentially prevent these reactions. If a severe infusion-related hypersensitivity reaction occurs, immediately discontinue VEKLURY and initiate appropriate treatment (see Contraindications).
• Increased risk of transaminase elevations: Transaminase elevations have been observed in healthy volunteers and in patients with COVID-19 who received VEKLURY; these elevations have also been reported as a clinical feature of COVID-19. Perform hepatic laboratory testing in all patients (see Dosage and administration). Consider discontinuing VEKLURY if ALT levels increase to >10× ULN. Discontinue VEKLURY if ALT elevation is accompanied by signs or symptoms of liver inflammation.
• Risk of reduced antiviral activity when coadministered with chloroquine or hydroxychloroquine: Coadministration of VEKLURY with chloroquine phosphate or hydroxychloroquine sulfate is not recommended based on data from cell culture experiments, demonstrating potential antagonism, which may lead to a decrease in the antiviral activity of VEKLURY.

Adverse reactions

• The most common adverse reaction (≥5% all grades) was nausea.
• The most common lab abnormalities (≥5% all grades) were increases in ALT and AST.

Drug interactions

• Drug interaction trials of VEKLURY and other concomitant medications have not been conducted in humans.

• Dosage: For adults and pediatric patients ≥12 years old and weighing ≥40 kg: 200 mg on Day 1, followed by once-daily maintenance doses of 100 mg from Day 2 administered only via intravenous infusion. VEKLURY should be initiated as soon as possible after diagnosis of symptomatic COVID-19.
• Treatment duration:

  -

  For hospitalized patients requiring invasive mechanical ventilation and/or ECMO, the recommended total treatment duration is 10 days.

  -

  For hospitalized patients not requiring invasive mechanical ventilation and/or ECMO, the recommended treatment duration is 5 days. If a patient does not demonstrate clinical improvement, treatment may be extended for up to 5 additional days, for a total treatment duration of up to 10 days.

  -

  For non-hospitalized patients diagnosed with mild-to-moderate COVID-19 who are at high risk for progression to severe COVID-19, including hospitalization or death, the recommended total treatment duration is 3 days.

• Testing prior to and during treatment: Perform eGFR, hepatic laboratory, and prothrombin time testing prior to initiating VEKLURY and during use as clinically appropriate.
• Renal impairment: VEKLURY is not recommended in individuals with eGFR <30 mL/min.
• Dose preparation and administration: See full Prescribing Information.

Pregnancy and lactation

• Pregnancy: A pregnancy registry has been established. There are insufficient human data on the use of VEKLURY during pregnancy. COVID-19 is associated with adverse maternal and fetal outcomes, including preeclampsia, eclampsia, preterm birth, premature rupture of membranes, venous thromboembolic disease, and fetal death.
• Lactation: It is not known whether VEKLURY can pass into breast milk. Breastfeeding individuals with COVID-19 should follow practices according to clinical guidelines to avoid exposing the infant to COVID-19.

Please see full Prescribing Information for VEKLURY, available at www.gilead.com.

FACT SHEET FOR HEALTHCARE PROVIDERS EMERGENCY USE AUTHORIZATION (EUA) OF VEKLURY® (remdesivir) FOR THE TREATMENT OF CORONAVIRUS DISEASE 2019 (COVID-19) IN PEDIATRIC PATIENTS WEIGHING 3.5 KG TO LESS THAN 40 KG OR PEDIATRIC PATIENTS LESS THAN 12 YEARS OF AGE WEIGHING AT LEAST 3.5 KG, WITH POSITIVE RESULTS OF DIRECT SARS-CoV-2 VIRAL TESTING 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

The U.S. Food and Drug Administration (FDA) has issued an Emergency Use Authorization (EUA) to permit the emergency use of VEKLURY for the treatment of coronavirus disease 2019 (COVID-19) in pediatric patients weighing 3.5 kg to less than 40 kg or pediatric patients less than 12 years of age weighing at least 3.5 kg, with positive results of direct severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral testing, 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. Refer to CDC website1 for additional details.

VEKLURY has been authorized by FDA for the emergency uses described above. VEKLURY is not FDA-approved for these uses.

VEKLURY is authorized only for the duration of the declaration that circumstances exist justifying the authorization of the emergency use of VEKLURY under section 564(b)(1) of the Act, 21 U.S.C. § 360bbb-3(b)(1), unless the authorization is terminated or revoked sooner.

1

https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/people-with-medical-conditions.html. Healthcare providers should consider the benefit-risk for an individual patient.

AUTHORIZED USE

VEKLURY is a drug approved for the treatment of coronavirus disease 2019 (COVID-19) in adults and pediatric patients (12 years of age and older and weighing at least 40 kg) with positive results of direct severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral testing, 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.

VEKLURY is not approved to treat pediatric patients weighing 3.5 kg to less than 40 kg or pediatric patients less than 12 years of age weighing at least 3.5 kg.

VEKLURY is authorized for use under an EUA for the treatment of COVID-19 in pediatric patients weighing 3.5 kg to less than 40 kg or pediatric patients less than 12 years of age weighing at least 3.5 kg, with positive results of direct SARS-CoV-2 viral testing, 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. Refer to CDC website2 for additional details.

For more information, see the long version of the "Fact Sheet for Healthcare Providers," available at https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization.

2

https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/people-with-medical-conditions.html. Healthcare providers should consider the benefit-risk for an individual patient.

INSTRUCTIONS FOR HEALTHCARE PROVIDERS

As the healthcare provider, you must communicate to the parent/caregiver and to your patient, as age appropriate, information consistent with the "Fact Sheet for Parents and Caregivers" (and provide a copy of the Fact Sheet) prior to the pediatric patient receiving VEKLURY, including:

• That FDA has authorized the emergency use of VEKLURY for the treatment of coronavirus disease 2019 (COVID-19) in pediatric patients weighing 3.5 kg to less than 40 kg or pediatric patients less than 12 years of age weighing at least 3.5 kg, with positive results of direct SARS-CoV-2 viral testing, 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.
• The parent/caregiver has the option to accept or refuse VEKLURY.
• The significant known and potential risks and benefits of VEKLURY, and the extent to which such risks and benefits are unknown.
• Information on available alternative treatments and the risks and benefits of those alternatives.

If providing this information will delay the administration of VEKLURY to a degree that would endanger the lives of patients, the information must be provided to the parent/caregiver as soon as feasible after VEKLURY is administered.

For information on clinical trials that are testing the use of VEKLURY for COVID-19, please see www.clinicaltrials.gov.

MANDATORY REQUIREMENTS FOR VEKLURY ADMINISTRATION UNDER EMERGENCY USE AUTHORIZATION:

In order to mitigate the risks of using this product under EUA and to optimize the potential benefit of VEKLURY for this use, the following items are required. Use of VEKLURY under this EUA is limited to the following (all requirements must be met):

1. VEKLURY is authorized for the treatment of COVID-19 in pediatric patients weighing 3.5 kg to less than 40 kg or pediatric patients less than 12 years of age weighing at least 3.5 kg, with positive results of direct SARS-CoV-2 viral testing, 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. Please refer to CDC website3 for additional details.
2. As the healthcare provider, communicate to the parent/caregiver and your patient, as age appropriate, information consistent with the "Fact Sheet for Parents and Caregivers" prior to the patient receiving VEKLURY. Healthcare providers (to the extent practicable given the circumstances of the emergency) must document in the patient's medical record that the parent/caregiver has been:
   • Given the "Fact Sheet for Parents and Caregivers,"
   • Informed of alternatives to receiving VEKLURY, and
   • Informed that VEKLURY is an approved drug that is authorized for this unapproved use under EUA.
3. 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 starting VEKLURY and monitored during treatment as clinically appropriate.
4. Perform hepatic laboratory testing in all patients before starting VEKLURY and during treatment as clinically appropriate.
5. Determine prothrombin time in all patients before starting VEKLURY and monitor during treatment as clinically appropriate.
6. Patients with known hypersensitivity to any ingredient of VEKLURY must not receive VEKLURY.
7. The prescribing healthcare provider and/or the provider's designee are/is responsible for mandatory reporting of all serious adverse events4 and medication errors potentially related to VEKLURY within 7 calendar days from the healthcare provider's awareness of the event, using FDA Form 3500 (for information on how to access this form, see below). The FDA requires that such reports, using FDA Form 3500, include the following:
   • Patient demographics and baseline characteristics (e.g., patient identifier, age or date of birth, gender, weight, ethnicity, and race)
   • A statement "Veklury (remdesivir) use for COVID-19 under Emergency Use Authorization (EUA)" under the "Describe Event, Problem, or Product Use/Medication Error" heading
   • Information about the serious adverse event or medication error (e.g., signs and symptoms, test/laboratory data, complications, timing of drug initiation in relation to the occurrence of the event, duration of the event, treatments required to mitigate the event, evidence of event improvement/disappearance after stopping or reducing the dosage, evidence of event reappearance after reintroduction, clinical outcomes).
   • Patient's preexisting medical conditions and use of concomitant products
   • Information about the product (e.g., dosage, route of administration, NDC #).
   Submit adverse event and medication error reports, using Form 3500, to FDA MedWatch using one of the following methods:
   • Complete and submit the report online: www.fda.gov/medwatch/report.htm
   • Complete and submit a postage-paid FDA Form 3500 (https://www.fda.gov/media/76299/download) and return by:
     • Mail to MedWatch, 5600 Fishers Lane, Rockville, MD 20852-9787, or
     • Fax to 1-800-FDA-0178, or
   • Call 1-800-FDA-1088 to request a reporting form
   In addition, please provide a copy of all FDA MedWatch forms to:
   Gilead Global Patient Safety
   Fax: 1-650-522-5477
   E-mail: [email protected]
   Or call Gilead at 1-800-GILEAD-5 to report adverse events
8. The prescribing healthcare provider and/or the provider's designee is/are responsible for mandatory responses to requests from FDA for information about adverse events and medication errors following receipt of VEKLURY.

3

https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/people-with-medical-conditions.html. Healthcare providers should consider the benefit-risk for an individual patient.

4

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.

APPROVED AVAILABLE ALTERNATIVES

There is no approved available alternative product for the treatment of COVID-19 in pediatric patients weighing 3.5 kg to less than 40 kg or pediatric patients less than 12 years of age weighing at least 3.5 kg, with positive results of direct SARS-CoV-2 viral testing, and 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.

There are EUAs for other COVID-19 treatments. Additional information on COVID-19 treatments can be found at https://www.covid19treatmentguidelines.nih.gov/. The healthcare provider should visit https://clinicaltrials.gov/ to determine whether the patient may be eligible for enrollment in a clinical trial.

AUTHORITY FOR ISSUANCE OF THE EUA

The Secretary of HHS has declared that circumstances exist that justify the emergency use of drugs and biological products during the COVID-19 pandemic. In response, the FDA has issued an EUA for the approved product, VEKLURY, for the unapproved use to treat COVID-19 in pediatric patients weighing 3.5 kg to less than 40 kg or pediatric patients less than 12 years of age weighing at least 3.5 kg, with positive results of direct SARS-CoV-2 viral testing, and who are5:

• 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. Please refer to CDC website6 for additional details.

FDA has issued this EUA, requested by Gilead Sciences, Inc. and based on their submitted data. As a healthcare provider, you must comply with the mandatory requirements of the EUA (see above).

Although limited scientific information is available in the pediatric population, based on the totality of the scientific evidence available to date, it is reasonable to believe that VEKLURY may be effective for the treatment of COVID-19 in pediatric patients as specified in this Fact Sheet. You may be contacted and asked to provide information to help with the assessment of the use of the product during this emergency.

This EUA for VEKLURY will end when the Secretary determines that the circumstances justifying the EUA no longer exist or when there is a change in the approval status of the product such that an EUA is no longer needed.

5

The healthcare provider should visit clinicaltrials.gov to determine whether there is an active clinical trial for the product in this disease/condition and whether enrollment of the patient(s) in a clinical trial is more appropriate than product use under this EUA.

6

https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/people-with-medical-conditions.html. Healthcare providers should consider the benefit-risk for an individual patient.

FULL EUA PRESCRIBING INFORMATION

1. AUTHORIZED USE

VEKLURY is authorized for use under an EUA for the treatment of coronavirus disease 2019 (COVID-19) in pediatric patients weighing 3.5 kg to less than 40 kg or pediatric patients less than 12 years of age weighing at least 3.5 kg, with positive results of direct severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral testing, 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. Refer to CDC website7 for additional details.

7

https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/people-with-medical-conditions.html. Healthcare providers should consider the benefit-risk for an individual patient.

2. Remdesivir Dosage and Administration

3. Dosage Forms and Strengths

VEKLURY for injection,100 mg, available as a sterile, preservative-free white to off-white to yellow lyophilized powder in single-dose vial for reconstitution.

4. Contraindications

VEKLURY is contraindicated in patients with a history of clinically significant hypersensitivity reactions to VEKLURY or any components of the product [see Warnings and Precautions (5.1)].

5. Warnings and Precautions

There are limited clinical data available for VEKLURY in pediatric patients weighing 3.5 kg to less than 40 kg or pediatric patients less than 12 years of age weighing at least 3.5 kg. Serious and unexpected adverse events may occur that have not been previously reported with VEKLURY use.

6. OVERALL SAFETY SUMMARY

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

7. PATIENT MONITORING RECOMMENDATIONS

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 (2.2, 2.4)].

Administration should be under conditions where management of severe hypersensitivity reactions, such as anaphylaxis, is possible. 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.

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 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 healthcare provider and/or the provider's designee are/is responsible for the mandatory reporting of all serious adverse events* and medication errors potentially related to VEKLURY within 7 calendar days from the healthcare provider's awareness of the event, using FDA Form 3500 (for information on how to access this form, see below). The FDA requires that such reports, using FDA Form 3500, include the following:

• Patient demographics and baseline characteristics (e.g., patient identifier, age or date of birth, gender, weight, ethnicity, and race)
• A statement "Veklury (remdesivir) use for COVID-19 under Emergency Use Authorization (EUA)" under the "Describe Event, Problem, or Product Use/Medication Error" heading
• Information about the serious adverse event or medication error (e.g., signs and symptoms, test/laboratory data, complications, timing of drug initiation in relation to the occurrence of the event, duration of the event, treatments required to mitigate the event, evidence of event improvement/disappearance after stopping or reducing the dosage, evidence of event reappearance after reintroduction, clinical outcomes)
• Patient's preexisting medical conditions and use of concomitant products
• Information about the product (e.g., dosage, route of administration, NDC #).

Submit adverse event and medication error reports, using Form 3500, to FDA MedWatch using one of the following methods:

• Complete and submit the report online: www.fda.gov/medwatch/report.htm
• Complete and submit a postage-paid FDA Form 3500 (https://www.fda.gov/media/76299/download) and return by:
  • Mail to MedWatch, 5600 Fishers Lane, Rockville, MD 20852-9787, or
  • Fax to 1-800-FDA-0178, or
• Call 1-800-FDA-1088 to request a reporting form

The prescribing healthcare provider and/or the provider's designee is/are responsible for mandatory responses to requests from FDA for information about adverse events and medication errors following receipt of VEKLURY.

*Serious adverse events are defined as:

• Death or a life-threatening adverse event;
• A medical or surgical intervention to prevent death, a life-threatening event, hospitalization, disability, or congenital anomaly;
• Inpatient hospitalization or prolongation of existing hospitalization;
• A persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions; or
• A congenital anomaly/birth defect.

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:

• In section A, box 1, provide the patient's initials in the Patient Identifier
• In section A, box 2, provide the patient's date of birth
• In section B, box 5, description of the event:
  • Write "Veklury (remdesivir) use for COVID-19 under Emergency Use Authorization (EUA)" as the first line
  • 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.
• In section G, box 1, name and address:
  • Provide the name and contact information of the prescribing healthcare provider or institutional designee who is responsible for the report.
  • Provide the address of the treating institution (NOT the healthcare provider's office address).

9. OTHER REPORTING REQUIREMENTS

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

Gilead Global Patient Safety

Fax: 1-650-522-5477

E-mail: [email protected]

Or call Gilead at 1-800-GILEAD-5 to report adverse events

10. Drug Interactions

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), Microbiology/Resistance Information (15)].

Clinical drug-drug interaction studies have not been performed with VEKLURY.

In vitro, remdesivir is a substrate for drug metabolizing enzyme 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, and MATE1. GS-704277 is a substrate for OATP1B1 and OATP1B3. The clinical relevance of these in vitro assessments has not been established.

Remdesivir is not a substrate for CYP1A1, 1A2, 2B6, 2C9, 2C19, or OATP1B3. GS-704277 and GS-441524 are not substrates for CYP1A1, 1A2, 2B6, 2C8, 2C9, 2D6, or 3A5. GS-441524 is also not a substrate for CYP2C19 or 3A4. GS-704277 and GS 441524 are not substrates for OAT1, OAT3, OCT1, OCT2, MATE1, or MATE2K. GS 441524 is also not a substrate for OATP1B1 or OATP1B3.

11. Use In Specific Populations

12. Overdosage

There is no human experience of acute overdosage with VEKLURY. 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. Remdesivir Description

VEKLURY contains remdesivir, a SARS-CoV-2 nucleotide analog 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:

14. Remdesivir - Clinical Pharmacology

15. MICROBIOLOGY/RESISTANCE INFORMATION

16. Nonclinical Toxicology

17. ANIMAL PHARMACOLOGIC AND EFFICACY DATA

• Remdesivir exhibited cell culture antiviral activity against a clinical isolate of SARS-CoV-2 in primary HAE cells (EC50 value= 9.9 nM) after 48 hours of treatment. Remdesivir inhibited the replication of SARS-CoV-2 in the continuous human lung epithelial cell line Calu-3 with an EC50 value of 280 nM after 72 hours of 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 is an antiviral drug with available data from four randomized clinical trials in adult patients with COVID-19. VEKLURY is approved for use to treat COVID-19 in adults and pediatric patients 12 years of age and older and weighing at least 40 kg. VEKLURY is not approved for use in pediatric patients weighing 3.5 kg to less than 40 kg or pediatric patients less than 12 years of age weighing at least 3.5 kg.

19. How is Remdesivir supplied

20. PATIENT COUNSELING INFORMATION

SEE Fact Sheet for Parents and Caregivers

21. CONTACT INFORMATION

If you have questions, please contact
www.askgileadmedical.com
1-866-633-4474

© 2022 Gilead Sciences, Inc. All rights reserved.
Revised: 01/2022

Fact Sheet for Parents and CaregiversEmergency Use Authorization (EUA) of VEKLURY® (remdesivir) for Coronavirus Disease 2019 (COVID-19) for Children Weighing 8 pounds (3.5 kg) to Less Than 88 pounds (40 kg) or for Children Less Than 12 Years of Age Weighing at least 8 pounds (3.5 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

You are being given this Fact Sheet because your healthcare provider believes it is necessary to provide your child with VEKLURY for use for the treatment of coronavirus disease 2019 (COVID-19). The United States Food and Drug Administration (FDA) has issued an Emergency Use Authorization (EUA) for VEKLURY for use in children weighing 8 pounds (3.5 kg) to less than 88 pounds (40 kg) or children less than 12 years of age weighing at least 8 pounds (3.5 kg) with positive results of direct severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral testing, 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.

This Fact Sheet contains information to help you understand the risks and benefits of your child receiving VEKLURY.

The FDA has issued an EUA to make VEKLURY available for this use during the COVID-19 pandemic (for more details about an EUA please see "What is an Emergency Use Authorization?" at the end of this document). VEKLURY is not approved for use as treatment for COVID-19 for the pediatric population covered under this EUA. Read this Fact Sheet for information about VEKLURY. Talk to your healthcare provider about your options or if you have any questions. It is your choice for your child to receive VEKLURY or stop it at any time.

What is COVID-19?

COVID-19 is caused by a virus called a coronavirus. You can get COVID-19 through close contact with another person who has the virus.

COVID-19 illnesses have ranged from very mild to severe, including illness with no reported symptoms and 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 a child's 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 is VEKLURY?

VEKLURY is a prescription medicine that is investigational for use for the treatment of COVID-19 in children weighing 8 pounds (3.5 kg) to less than 88 pounds (40 kg) or children less than 12 years of age weighing at least 8 pounds (3.5 kg) with positive results of direct SARS-CoV-2 viral testing, 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.

VEKLURY is investigational for this use because it is still being studied and there is limited information about the safety and effectiveness of using VEKLURY for the treatment of COVID-19 in this population.

VEKLURY is an FDA-approved prescription medicine used to treat COVID-19 in adults and children (12 years of age and older and weighing at least 88 pounds (40 kg), with positive results of direct SARS-CoV-2 viral testing, who are:

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

What should I tell my healthcare provider before my child receives VEKLURY?

Tell your healthcare provider about all of your child's medical conditions, including if your child:

• Has any allergies
• Has kidney or liver disease
• Has any serious illnesses

Tell your healthcare provider about all the medicines your child takes, including prescription and over-the-counter medicines, vitamins, and herbal supplements. VEKLURY may interact with other medicines and may cause serious side effects.

Especially tell your healthcare provider if your child is taking the medicines chloroquine phosphate or hydroxychloroquine sulfate.

How will my child receive VEKLURY?

• Hospitalized: VEKLURY is given to your child through a vein by intravenous (IV) infusion one time each day for up to 10 days. Your healthcare provider will decide how many doses your child needs.
• Not hospitalized: VEKLURY is given to your child 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.

Who should generally not receive VEKLURY?

Your child should not receive VEKLURY if your child is allergic to remdesivir or any of the ingredients in VEKLURY.

What are the important possible side effects of VEKLURY?

Possible side effects of VEKLURY are:

• Allergic reactions. Allergic reactions can happen during and after infusion with VEKLURY. Your healthcare provider will monitor your child for signs and symptoms of allergic reactions during their infusion and for at least 1 hour after their infusion. Tell your healthcare provider right away if your child gets any of the following signs and symptoms of allergic reactions:

  changes to heart rate fever shortness of breath or wheezing shivering

  swelling of the lips, face, or throat rash nausea sweating

• Increases in levels of liver enzymes. Increases in liver enzymes are common in people who have received VEKLURY and may be a sign of liver injury. Your healthcare provider will do blood tests to check your child's liver enzymes before receiving VEKLURY and as needed while receiving VEKLURY. Your healthcare provider may stop treatment with VEKLURY if your child develops liver problems.

The most common side effect of VEKLURY is nausea.

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.

What other treatment choices are there?

Like VEKLURY, FDA may allow for the emergency use of other medicines to treat people with COVID-19. Go to https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization for information on the emergency use of other medicines that are not approved by the FDA to treat people with COVID-19. Your healthcare provider may talk with you about clinical trials your child may be eligible for.

It is your choice for your child to be treated or not to be treated with VEKLURY. Should you decide for your child not to receive it, it will not change your child's standard medical care.

How do I report side effects with VEKLURY?

Contact your healthcare provider if your child has any side effect that bothers them or does not go away.

Report side effects to FDA MedWatch at www.fda.gov/medwatch or call 1-800-FDA-1088 and to Gilead by calling 1-800-445-3235.

How can I learn more about COVID-19?

• Ask your healthcare provider.
• Visit https://www.cdc.gov/COVID19.
• Contact your local or state public health department.

The United States FDA has made VEKLURY available under an emergency access mechanism called an Emergency Use Authorization (EUA) for the treatment of coronavirus disease 2019 (COVID-19) in children weighing 8 pounds (3.5 kg) to less than 88 pounds (40 kg) or children less than 12 years of age weighing at least 8 pounds (3.5 kg), with positive results of direct severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral testing, 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.

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 for the authorized use has not undergone the same type of review as an FDA-approved product. In issuing an EUA under the COVID-19 public health emergency, the FDA has determined, among other things, that based on the total amount of scientific evidence available including data from adequate and well controlled clinical trials, it is reasonable to believe that the product may be effective for diagnosing, treating, or preventing COVID-19, or a serious or life threatening disease or condition caused by COVID-19; that the known and potential benefits of the product, when used to diagnose, treat, or prevent such disease or condition, outweigh the known and potential risks of such product; and that there are no adequate, approved, and available alternatives.

All of these criteria must be met to allow for the product to be used in the treatment of the authorized patient population during the COVID-19 pandemic. The EUA for VEKLURY is in effect for the duration of the COVID-19 declaration justifying emergency use of VEKLURY, unless terminated or revoked (after which VEKLURY may no longer be used under the EUA).

© 2022 Gilead Sciences, Inc. All rights reserved.
Revised: 01/2022

PRINCIPAL DISPLAY PANEL - 100 mg/20 mL Vial Label

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

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

For use under Emergency
Use Authorization (EUA)

90286902
Rx only

PRINCIPAL DISPLAY PANEL - 100 mg/20 mL Vial Carton

61958-2902-1
Rx only

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

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

For use under Emergency
Use Authorization (EUA)

Each mL contains 5 mg
of remdesivir in 20 mL solution

GILEAD

PRINCIPAL DISPLAY PANEL - 100 mg Vial Label

remdesivir
for injection
100 mg/vial

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

For use under Emergency
Use Authorization (EUA)

90287202
Rx only

PRINCIPAL DISPLAY PANEL - 100 mg Vial Carton

61958-2901-1
Rx only

remdesivir
for injection
100 mg/vial

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

For use under Emergency
Use Authorization (EUA)

Each vial contains 100 mg
of remdesivir lyophilized

GILEAD