IMPORTANT PRESCRIBING INFORMATION

Subject:

Updated Emergency Use Authorization (EUA) for hospitalized pediatric patients weighing 3.5 kg to less than 40 kg or hospitalized pediatric patients less than 12 years of age weighing at least 3.5 kg with suspected or laboratory-confirmed COVID-19 and variations in carton and vial labeling of VEKLURY ® (remdesivir)

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 October 22, 2020, for adults and pediatric patients (12 years and older and weighing at least 40 kg) for the treatment of coronavirus disease 2019 (COVID-19) requiring hospitalization. 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) in hospitalized pediatric patients weighing 3.5 kg to less than 40 kg or hospitalized pediatric patients less than 12 years of age weighing at least 3.5 kg with suspected or laboratory-confirmed COVID-19

On October 22, 2020, FDA revised the Emergency Use Authorization (EUA) for VEKLURY, which now authorizes VEKLURY for use by healthcare providers to treat hospitalized pediatric patients weighing 3.5 kg to less than 40 kg or hospitalized pediatric patients less than 12 years of age weighing at least 3.5 kg with suspected or laboratory-confirmed COVID-19. 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 in hospitalized pediatric patients weighing 3.5 kg to less than 40 kg or hospitalized pediatric patients less than 12 years of age weighing at least 3.5 kg for the treatment of suspected or laboratory-confirmed COVID-19 has not been established, and VEKLURY is not FDA approved for this use. For information about the authorized use of VEKLURY in hospitalized pediatric patients weighing 3.5 kg to less than 40 kg or hospitalized 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.

Healthcare providers are encouraged to report all adverse events and medication errors when utilizing VEKLURY to Gilead Sciences at Safety_fc@gilead.com. Adverse reactions, medication errors, or quality problems experienced with the use of this product may be reported to the FDA's MedWatch Adverse Event Reporting program either online, by regular mail or by fax.

• Complete and submit the report Online: www.fda.gov/medwatch/report.htm
• Regular Mail or Fax: Download form https://www.accessdata.fda.gov/scripts/medwatch/index.cfm or call 1-800-332-1088 to request a reporting form, then complete and return to the address on the pre-addressed form, or submit by fax to 1-800-FDA-0178 (1-800-332-0178).

For emergency use in hospitalized pediatric patients weighing 3.5 kg to less than 40 kg or hospitalized pediatric patients less than 12 years of age weighing at least 3.5 kg, healthcare providers and/or their designee are responsible for mandatory FDA MedWatch reporting of all medication errors and serious adverse events or deaths occurring during VEKLURY treatment and considered to be potentially attributable to VEKLURY. These events must be reported within 7 calendar days from the onset of the event. MedWatch adverse event reports can be submitted to FDA online at www.fda.gov/medwatch or by calling 1-800-FDA-1088.

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

Information and reports of suspicious, counterfeit, or unregistered remdesivir can be submitted to Gilead anticounterfeiting@gilead.com and/or www.fraud.org/fakerx.

Appropriate use of Gilead's remdesivir (brand name VEKLURY), including vials labeled for Emergency Use Authorization (EUA) use

Product	Remdesivir for injection, 100 mg, lyophilized powder	Remdesivir injection, 100 mg/20 mL (5 mg/mL), solution
Labeled "For use under Emergency Use Authorization (EUA)" (vials and cartons do not include the brand name, VEKLURY)	Continue use in: Adults and pediatric patients (12 years of age and older and weighing at least 40 kg) requiring hospitalization Hospitalized pediatric patients weighing 3.5 kg to less than 40 kg or hospitalized pediatric patients less than 12 years of age weighing at least 3.5 kg under the provisions of the Emergency Use Authorization (EUA) – Please review the EUA Fact Sheet for Healthcare Providers and FDA Letter of Authorization , available at gilead.com/remdesivir.	Continue use in: Adults and pediatric patients (12 years of age and older and weighing at least 40 kg) requiring hospitalization
FDA-approved VEKLURY (carton and vials will include the brand name, VEKLURY)	Use in: Adults and pediatric patients (12 years of age and older and weighing at least 40 kg) requiring hospitalization Hospitalized pediatric patients weighing 3.5 kg to less than 40 kg or hospitalized pediatric patients less than 12 years of age weighing at least 3.5 kg under the provisions of the Emergency Use Authorization (EUA) – Please review the EUA Fact Sheet for Healthcare Providers and FDA Letter of Authorization, available at gilead.com/remdesivir.	Use in: Adults and pediatric patients (12 years of age and older and weighing at least 40 kg) requiring hospitalization

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

Indication

VEKLURY is indicated 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) requiring hospitalization. VEKLURY should only be administered in a hospital or in a healthcare setting capable of providing acute care comparable to inpatient hospital care.

Important Safety Information

Contraindication

• 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. Monitor patients under close medical supervision for hypersensitivity reactions during and following administration of VEKLURY. Symptoms may include hypotension, hypertension, tachycardia, bradycardia, hypoxia, fever, dyspnea, wheezing, angioedema, rash, nausea, diaphoresis, and shivering. Slower infusion rates (maximum infusion time ≤120 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 due to antagonism observed in cell culture, which may lead to a decrease in 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 and administration

• 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 over 30 to 120 minutes.
• Treatment duration: For patients not requiring invasive mechanical ventilation and/or extracorporeal membrane oxygenation (ECMO): 5 days; may be extended up to 5 additional days (10 days total) if clinical improvement is not observed. For patients requiring invasive mechanical ventilation and/or ECMO: 10 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: There are insufficient human data on the use of VEKLURY during pregnancy. Pregnant women hospitalized with COVID-19 are at risk for serious morbidity and mortality. VEKLURY should be used during pregnancy only if the potential benefit justifies the potential risk for the mother and the fetus.
• 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.

The U.S. Food and Drug Administration (FDA) has issued an Emergency Use Authorization (EUA) to permit the emergency use of VEKLURY for treatment of suspected or laboratory confirmed coronavirus disease 2019 (COVID-19) in hospitalized pediatric patients weighing 3.5 kg to less than 40 kg or hospitalized pediatric patients less than 12 years of age weighing at least 3.5 kg.

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.

AUTHORIZED USE

VEKLURY is a drug approved in 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) requiring hospitalization. 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 treatment of hospitalized pediatric patients weighing 3.5 kg to less than 40 kg or hospitalized pediatric patients less than 12 years of age weighing at least 3.5 kg with suspected or laboratory confirmed coronavirus disease 2019 (COVID-19) for whom use of an intravenous (IV) agent is clinically appropriate. 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.

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 treatment of suspected or laboratory confirmed COVID-19 in hospitalized pediatric patients weighing 3.5 kg to less than 40 kg or hospitalized pediatric patients less than 12 years of age weighing at least 3.5 kg for whom use of an IV agent is clinically appropriate and who are under the care or consultation of a licensed clinician skilled in the diagnosis and management of patients with potentially life-threatening illness and medication-related adverse events.
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 responses to requests from FDA for information about adverse events and medication errors following administration of VEKLURY.
8. The prescribing healthcare provider and/or the provider's designee are/is responsible for mandatory reporting of all medication errors and serious adverse events 1 considered to be potentially related to VEKLURY occurring during VEKLURY treatment within 7 calendar days from the onset of the event. The reports should include unique identifiers and the words "VEKLURY (remdesivir) under Emergency Use Authorization (EUA)" in the description section of the report.
   • Submit adverse event reports to FDA MedWatch using one of the following methods:
     • Complete and submit the report online: www.fda.gov/medwatch/report.htm, or
     • By using 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
     • Submitted reports should include in the field name, "Describe Event, Problem, or Product Use/Medication Error" a statement "VEKLURY (remdesivir) under Emergency Use Authorization (EUA)."

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: Safety_fc@gilead.com

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

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1

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. [see Full EUA Prescribing Information, Adverse Reactions and Medication Errors Reporting Requirements and Instructions (8)]

APPROVED AVAILABLE ALTERNATIVES

There is no approved available alternative product for treating 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 hospitalized with COVID-19. 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 hospitalized pediatric patients weighing 3.5 kg to less than 40 kg or hospitalized pediatric patients less than 12 years of age weighing at least 3.5 kg with COVID-19 2. 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.

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2

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.

FULL EUA PRESCRIBING INFORMATION

FULL EUA PRESCRIBING INFORMATION:	9 OTHER REPORTING REQUIREMENTS
CONTENTS*	10 DRUG INTERACTIONS
1 AUTHORIZED USE	11 USE IN SPECIFIC POPULATIONS
2 DOSAGE AND ADMINISTRATION	11.1 Pregnancy
2.1 Important Testing Before and During	11.2 Lactation
Treatment	11.3 Pediatric Use
2.2 Recommended Dosage in Pediatric Patients	11.4 Renal Impairment
2.3 Renal Impairment	11.5 Hepatic Impairment
2.4 Dose Preparation and Administration,	12 OVERDOSAGE
VEKLURY for Injection	13 PRODUCT DESCRIPTION
2.5 Storage of Prepared Dosages	13.1 Physical Appearance
3 DOSAGE FORMS AND STRENGTHS	13.2 Inactive Ingredients
4 CONTRAINDICATIONS	14 CLINICAL PHARMACOLOGY
5 WARNINGS AND PRECAUTIONS	14.1 Mechanism of Action
5.1 Hypersensitivity Including Infusion-Related and	14.2 Pharmacokinetics
Anaphylactic Reactions	15 MICROBIOLOGY/RESISTANCE INFORMATION
5.2 Increased Risk of Transaminase Elevations	16 NONCLINICAL TOXICOLOGY
5.3 Risk of Reduced Antiviral Activity When	17 ANIMAL PHARMACOLOGIC AND EFFICACY
Coadministered with Chloroquine Phosphate or	DATA
Hydroxychloroquine Sulfate	18 CLINICAL TRIAL RESULTS AND SUPPORTING
6 OVERALL SAFETY SUMMARY	DATA FOR EUA
6.1 Clinical Trials Experience	19 HOW SUPPLIED/STORAGE AND HANDLING
7 PATIENT MONITORING RECOMMENDATIONS	20 PATIENT COUNSELING INFORMATION
8 ADVERSE REACTIONS AND MEDICATION	21 CONTACT INFORMATION
ERRORS REPORTING REQUIREMENTS AND	*Sections or subsections omitted from the full
INSTRUCTIONS	prescribing information are not listed.

1. AUTHORIZED USE

VEKLURY is authorized for use under an EUA for treatment of hospitalized pediatric patients weighing 3.5 kg to less than 40 kg or hospitalized pediatric patients less than 12 years of age weighing at least 3.5 kg with suspected or laboratory confirmed coronavirus disease 2019 (COVID-19) for whom use of an intravenous (IV) agent is clinically appropriate.

2. 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 (2.1)] .

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 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 medication errors and the following selected serious adverse events occurring during VEKLURY 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:

• 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 healthcare 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:

• 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) 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: Safety_fc@gilead.com

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

10. DRUG INTERACTIONS

Due to antagonism observed in cell culture, 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. PRODUCT 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 C 27H 35N 6O 8P and a molecular weight of 602.6 g/mol. Remdesivir has the following structural formula:

14. 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 (EC 50 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 EC 50 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 three 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 SUPPLIED/STORAGE AND HANDLING

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

© 2020 Gilead Sciences, Inc. All rights reserved.
Revised: 10/2020

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

Your child is being given a medicine called VEKLURY. VEKLURY is a medicine approved for adults and children 12 years of age and older and weighing at least 88 pounds (40 kg) for the treatment of coronavirus disease 2019 (COVID-19) requiring hospitalization. It is not known if VEKLURY is safe and effective for the treatment of COVID-19 in hospitalized children weighing 8 pounds (3.5 kg) to less than 88 pounds (40 kg) or hospitalized children less than 12 years of age weighing at least 8 pounds (3.5 kg), and VEKLURY is not FDA approved for this use. This Fact Sheet contains information to help you understand the potential risks and potential benefits of your child receiving VEKLURY.

Read this Fact Sheet for information about VEKLURY. Talk to your healthcare provider if you have questions. It is your choice for your child to receive VEKLURY or to stop it at any time.

What is COVID-19?

COVID-19 is caused by a virus called a coronavirus. People 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 a child's other medical conditions to become worse. 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 child's other medical conditions to become worse.

What is VEKLURY?

VEKLURY is an approved antiviral medicine for adults and children 12 years of age and older and weighing at least 88 pounds (40 kg) for the treatment of COVID-19 requiring hospitalization. VEKLURY was shown in clinical trials in adults to shorten the time to recovery in some people.

VEKLURY is still being studied in hospitalized children.

There are no medicines approved by the FDA as safe and effective to treat hospitalized children weighing 8 pounds (3.5 kg) to less than 88 pounds (40 kg) or hospitalized children younger than 12 years of age weighing at least 8 pounds (3.5 kg) who have COVID-19. Therefore, the FDA has authorized the emergency use of VEKLURY for this use 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 my child receives VEKLURY?

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

• Has kidney problems
• Has liver problems
• Is taking any medicines (prescription, over-the-counter, vitamins, or herbal products). VEKLURY may interact with other medicines.
  • Especially tell your healthcare provider if you r child is taking the medicines chloroquine phosphate or hydroxychloroquine sulfate.

How will my child receive VEKLURY?

VEKLURY is given to your child through a vein (intravenous or IV) one time each day for up to 10 days. Your healthcare provider will decide how many doses your child needs.

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. 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, wheezing, swelling of the lips, face, or throat, rash, nausea, sweating, or shivering.
• 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 new or worsening 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.

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 hospitalized children weighing 8 pounds (3.5 kg) to less than 88 pounds (40 kg) or hospitalized children younger than 12 years of age weighing at least 8 pounds (3.5 kg) with COVID-19. Go to https://www.covid19treatmentguidelines.nih.gov/ for information on the emergency use of other medicines that are not approved by the FDA to treat people in the hospital 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 not to receive VEKLURY or to stop it at any time, it will not change your child's standard medical care.

How do I report side effects with VEKLURY?

Tell your healthcare provider right away 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-GILEAD-5.

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 to hospitalized children weighing 8 pounds (3.5 kg) to less than 88 pounds (40 kg) or hospitalized children less than 12 years of age weighing at least 8 pounds (3.5 kg) 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.

The 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 hospitalized children weighing 8 pounds (3.5 kg) to less than 88 pounds (40 kg) or hospitalized children less than 12 years of age weighing at least 8 pounds (3.5 kg) during the COVID-19 pandemic, and that the known and potential benefits outweigh the known and potential risks for such use.

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

© 2020 Gilead Sciences, Inc. All rights reserved.
Revised: 10/2020

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