1 FACT SHEET FOR HEALTH CARE PROVIDERS 2 EMERGENCY USE AUTHORIZATION (EUA) OF REMDESIVIR (GS-5734™) 3 4 The U.S. Food and Drug Administration (FDA) has issued an Emergency Use 5 Authorization (EUA) to permit the emergency use of the unapproved product 6 remdesivir for treatment of suspected or laboratory confirmed coronavirus 7 disease 2019 (COVID-19) in adults and children hospitalized with severe 8 disease. Severe disease is defined as patients with an oxygen saturation (SpO2) 9 ≤ 94% on room air or requiring supplemental oxygen or requiring mechanical 10 ventilation or requiring extracorporeal membrane oxygenation (ECMO). 11

This EUA is for the use of remdesivir to treat COVID-19 Remdesivir must be administered by intravenous (IV) infusion

Health care providers must submit a report on all medication errors and ALL SERIOUS ADVERSE EVENTS related to remdesivir. See specific reporting instructions below.

The optimal duration of treatment for COVID-19 is unknown. Under this EUA for remdesivir to treat COVID-19: • The suggested dose for adults and pediatric patients weighing ≥40 kg requiring invasive mechanical ventilation and/or ECMO is a single loading dose of 200 mg infused intravenously over 30 to 120 minutes on Day 1 followed by once-daily maintenance doses of 100 mg infused intravenously over 30 to 120 minutes for 9 days (days 2 through 10). • The suggested dose for adults and pediatric patients weighing ≥40 kg not requiring invasive mechanical ventilation and/or ECMO is a single dose of 200 mg infused intravenously over 30 to 120 minutes on Day 1 followed by once-daily maintenance doses of 100 mg infused intravenously over 30 to 120 minutes for 4 days (days 2 through 5). If a patient does not demonstrate clinical improvement, treatment may be extended for up to 5 additional days (i.e., up to a total of 10 days). • The suggested dose for pediatric patients with body weight between 3.5 kg and <40 kg requiring invasive mechanical ventilation and/or ECMO is a single loading dose of remdesivir 5 mg/kg IV (infused over 30 to 120 min) on Day 1 followed by remdesivir 2.5 mg/kg IV (infused over 30 to 120 min) once daily for 9 days (days 2 through 10). • The suggested dose for pediatric patients with body weight between 3.5 kg and <40 kg not requiring invasive mechanical ventilation and/or ECMO is a single loading dose of remdesivir 5 mg/kg IV (infused over 30 to 120 min) on Day 1 followed by remdesivir 2.5 mg/kg IV (infused over 30 to 120 min) once daily for 4 days (days 2 through 5). If a patient does not demonstrate clinical improvement, treatment may be extended for up to 5 additional days (i.e., up to a total of 10 days).

1 For information on clinical trials that are testing the use of remdesivir in COVID-19, please see www.clinicaltrials.gov. 12 13 INSTRUCTIONS FOR ADMINISTRATION 14 15 This section provides essential information on the unapproved use of remdesivir, 16 an unapproved drug, to treat suspected or laboratory confirmed COVID-19 in 17 adults and children hospitalized with severe disease under this EUA. For more 18 information, see the long version of the “Fact Sheet for Health Care Providers,” 19 available at https://www.fda.gov/emergency-preparedness-and-response/mcm- 20 legal-regulatory-and-policy-framework/emergency-use-authorization. 21 Contraindications 22 23 Remdesivir is contraindicated in patients with known hypersensitivity to any 24 ingredient of remdesivir. 25 26 Dosing

27 Treatment Initiation and Dosing Regimens 28 • Empiric treatment of hospitalized patients with suspected COVID-19 can 29 be considered pending laboratory confirmation of SARS-CoV-2 infection. 30 • A treatment course of 10 days is recommended for adults and pediatric 31 patients requiring invasive mechanical ventilation and/or extracorporeal 32 membrane oxygenation. 33 • A treatment course of 5 days is recommended for adults and pediatric 34 patients not requiring invasive mechanical ventilation and/or ECMO. If a 35 patient does not demonstrate clinical improvement, treatment may be 36 extended for up to 5 additional days (i.e., up to a total of 10 days). 37 • Remdesivir can be used at any time after onset of symptoms in 38 hospitalized patients. 39 • All patients must have an estimated glomerular filtration rate (eGFR) 40 determined before dosing. 41 • Hepatic laboratory testing should be performed in all patients prior to 42 starting remdesivir and daily while receiving remdesivir. 43 44 Adult Patients 45 • For adults requiring invasive mechanical ventilation and/or ECMO, the 46 dosage of remdesivir is a single loading dose of 200 mg infused 47 intravenously over 30 to 120 minutes on Day 1 followed by once-daily 48 maintenance doses of 100 mg infused intravenously over 30 to 120 49 minutes for 9 days (days 2 through 10). 50 • For adults not requiring invasive mechanical ventilation and/or ECMO, the 51 dosage of remdesivir is a single loading dose of 200 mg infused 52 intravenously over 30 to 120 minutes on Day 1 followed by once-daily 53 maintenance doses of 100 mg infused intravenously over 30 to 120

2 54 minutes for 4 days (days 2 through 5). If a patient does not demonstrate 55 clinical improvement, treatment may be extended for up to 5 additional 56 days (i.e., up to a total of 10 days). 57 58 Pediatric Patients 59 • For pediatric patients with body weight ≥40 kg requiring invasive 60 mechanical ventilation and/or ECMO, the adult dosage regimen of one 61 loading dose of remdesivir 200 mg IV (infused over 30 to 120 minutes) on 62 Day 1 followed by remdesivir 100 mg IV (infused over 30 to 120 minutes) 63 once daily for 9 days (days 2 through 10) will be administered. 64 • For pediatric patients with body weight ≥40 kg not requiring invasive 65 mechanical ventilation and/or ECMO, the adult dosage regimen of one 66 loading dose of remdesivir 200 mg IV (infused over 30 to 120 minutes) on 67 Day 1 followed by remdesivir 100 mg IV (infused over 30 to 120 minutes) 68 once daily for 4 days (days 2 through 5) will be administered. If a patient 69 does not demonstrate clinical improvement, treatment may be extended 70 for up to 5 additional days (i.e., up to a total of 10 days). 71 • Use of the adult dose in these pediatric patients is expected to maintain 72 exposures of both remdesivir and the nucleoside analog GS-441524 73 generally within the expected adult steady-state exposure range following 74 administration of the adult therapeutic dosage regimen in healthy 75 volunteers. 76 • For pediatric patients with body weight between 3.5 kg and <40 kg, use 77 remdesivir for injection, 100 mg, lyophilized powder only. Administer a 78 body weight-based dosing regimen of one loading dose of remdesivir 5 79 mg/kg IV (infused over 30 to 120 min) on Day 1 followed by remdesivir 2.5 80 mg/kg IV (infused over 30 to 120 min) once daily for 9 days (for pediatric 81 patients requiring invasive mechanical ventilation and/or ECMO, days 2 82 through 10) or for 4 days (for pediatric patients not requiring invasive 83 mechanical ventilation and/or ECMO, days 2 through 5). If a patient does 84 not demonstrate clinical improvement, treatment may be extended for up 85 to 5 additional days (i.e., up to a total of 10 days). Use of this weight- 86 based dosing regimen is expected to maintain remdesivir exposure that is 87 comparable to that observed in adults while limiting the exposure of the 88 nucleoside analog GS-441524 in very young children. 89 90 Pregnancy 91 Remdesivir should be used during pregnancy only if the potential benefit justifies 92 the potential risk for the mother and the fetus. 93 94 Renal Impairment 95 The pharmacokinetics of remdesivir have not been evaluated in patients with 96 renal impairment. Use in patients with renal impairment are based on potential 97 risk and potential benefit considerations. Patients with eGFR greater than or 98 equal to 30 mL/min have received remdesivir for treatment of COVID-19 with no 99 dose adjustment of remdesivir.

3 100 101 All patients must have an eGFR determined before dosing. Remdesivir is not 102 recommended in adult and pediatric patients (>28 days old) with eGFR less than 103 30 mL/min or in full-term neonates (≥7 days to ≤28 days old) with serum 104 creatinine greater than or equal to 1 mg/dL unless the potential benefit outweighs 105 the potential risk. 106 107 Hepatic Impairment 108 The pharmacokinetics of remdesivir have not been evaluated in patients with 109 hepatic impairment. It is not known if dosage adjustment is needed in patients 110 with hepatic impairment and remdesivir should only be used in patients with 111 hepatic impairment if the potential benefit outweighs the potential risk. 112 113 Hepatic laboratory testing should be performed in all patients prior to starting 114 remdesivir and daily while receiving remdesivir. 115 116 Dose Preparation 117 Care should be taken during admixture to prevent inadvertent microbial 118 contamination. As there is no preservative or bacteriostatic agent present in this 119 product, aseptic technique must be used in preparation of the final parenteral 120 solution. It is always recommended to administer IV medication immediately after 121 preparation when possible. 122 123 Store diluted remdesivir solution for infusion up to 4 hours at room temperature 124 (20°C to 25°C [68°F to 77°F]) or 24 hours at refrigerated temperature (2°C to 8°C 125 [36°F to 46°F]).

126 Important Preparation and Administration Instructions

127 • Remdesivir for Injection, 100 mg: Reconstitute remdesivir for injection 128 lyophilized powder with 19 mL of Sterile Water for Injection and dilute in 129 0.9% saline prior to administration. 130 • Remdesivir Injection, 5 mg/mL: Dilute remdesivir injection concentrated 131 solution in 0.9% saline prior to administration. 132 • Prepare solution for infusion on same day as administration. 133 • Administer remdesivir as an intravenous infusion over 30 to 120 minutes. 134 • After infusion is complete, flush with at least 30 mL of 0.9% saline. 135 • Discard any remaining reconstituted remdesivir lyophilized powder, 136 reconcentrated solution, and diluted solution. 137 138 Storage and Handling of Prepared Dosages 139 140 IMPORTANT: 141 This product contains no preservative. Any unused portion of a single-dose 142 remdesivir vial should be discarded after a diluted solution is prepared.

4 143 Parenteral drug products should be inspected visually for particulate matter and 144 discoloration prior to administration, whenever solution and container permit. 145 Should either be observed, the solution should be discarded and fresh solution 146 prepared.

147 The prepared diluted solution should not be administered simultaneously with 148 any other medication. The compatibility of remdesivir injection with IV solutions 149 and medications other than 0.9% saline is not known.

150 Warnings 151 There are limited clinical data available for remdesivir. Serious and unexpected 152 adverse events may occur that have not been previously reported with remdesivir 153 use. 154 155 Infusion-Related Reactions 156 157 Infusion-related reactions have been observed during, and/or have been 158 temporally associated with, administration of remdesivir. Signs and symptoms 159 may include hypotension, nausea, vomiting, diaphoresis, and shivering. If signs 160 and symptoms of a clinically significant infusion reaction occur, immediately 161 discontinue administration of remdesivir and initiate appropriate treatment. The 162 use of remdesivir is contraindicated in patients with known hypersensitivity to 163 remdesivir. 164 165 Increased Risk of Transaminase Elevations 166 167 Transaminase elevations have been observed in the remdesivir clinical 168 development program, including in healthy volunteers and patients with COVID- 169 19. In healthy volunteers who received up to 150 mg daily for 14 days, alanine 170 aminotransferase (ALT) elevations were observed in the majority of patients, 171 including elevations up to 10 times baseline values in one subject without 172 evidence of clinical hepatitis; no ≥ Grade 3 adverse events were observed. 173 Transaminase elevations have also been reported in patients with COVID-19 174 who received remdesivir, including one patient with ALT elevation up to 20 times 175 the upper limit of normal. As transaminase elevations have been reported as a 176 component of COVID-19 in some patients, discerning the contribution of 177 remdesivir to transaminase elevations in this patient population is challenging.

5 178 179 Hepatic laboratory testing should be performed in all patients prior to starting 180 remdesivir and daily while receiving remdesivir. 181 • Remdesivir should not be initiated in patients with ALT ≥ 5 times the upper 182 limit of normal at baseline 183 • Remdesivir should be discontinued in patients who develop: 184 o ALT ≥ 5 times the upper limit of normal during treatment with 185 remdesivir. Remdesivir may be restarted when ALT is < 5 times the 186 upper limit of normal. 187 OR 188 o ALT elevation accompanied by signs or symptoms of liver 189 inflammation or increasing conjugated bilirubin, alkaline 190 phosphatase, or INR 191 192 Serious Side Effects 193 An adverse reaction associated with remdesivir in clinical trials in healthy adult 194 subjects was increased liver transaminases. Additional adverse reactions 195 associated with the drug, some of which may be serious, may become apparent 196 with more widespread use. 197 198 INSTRUCTIONS FOR HEALTH CARE PROVIDERS 199 200 As the health care provider, you must communicate to your patient or 201 parent/caregiver information consistent with the “Fact Sheet for Patients and 202 Parents/Caregivers” (and provide a copy of the Fact Sheet) prior to the patient 203 receiving remdesivir, including: 204 • FDA has authorized the emergency use of remdesivir, which is not an 205 FDA approved drug. 206 • The patient or parent/caregiver has the option to accept or refuse 207 remdesivir. 208 • The significant known and potential risks and benefits of remdesivir, and 209 the extent to which such risks and benefits are unknown. 210 • Information on available alternative treatments and the risks and benefits 211 of those alternatives. 212 213 If providing this information will delay the administration of remdesivir to a degree 214 that would endanger the lives of patients, the information must be provided to the 215 patients as soon as practicable after remdesivir is administered. 216 217 For information on clinical trials that are testing the use of remdesivir for COVID- 218 19, please see www.clinicaltrials.gov. 219

6 220 MANDATORY REQUIREMENTS FOR REMDESIVIR ADMINISTRATION 221 UNDER EMERGENCY USE AUTHORIZATION: 222 223 In order to mitigate the risks of using this unapproved product under EUA and to 224 optimize the potential benefit of remdesivir, the following items are required. Use 225 of unapproved remdesivir under this EUA is limited to the following (all 226 requirements must be met): 227 228 1. Treatment of suspected or laboratory confirmed coronavirus disease 2019 229 (COVID-19) in adults and children hospitalized with severe disease. 230 Severe disease is defined as patients with an oxygen saturation (SpO2) 231 ≤ 94% on room air or requiring supplemental oxygen or requiring invasive 232 mechanical ventilation or requiring ECMO. Specifically, remdesivir is 233 authorized only for the following patients who are admitted to a hospital 234 and under the care or consultation of a licensed clinician (skilled in the 235 diagnosis and management of patients with potentially life-threatening 236 illness and the ability to recognize and manage medication-related 237 adverse events): 238 a. Adult patients for whom use of an IV agent is clinically appropriate. 239 b. Pediatric patients for whom use of an IV agent is clinically 240 appropriate. 241 2. As the health care provider, communicate to your patient or 242 parent/caregiver information consistent with the “Fact Sheet for Patients 243 and Parents/Caregivers” prior to the patient receiving remdesivir. Health 244 care providers (to the extent practicable given the circumstances of the 245 emergency) must document in the patient’s medical record that the 246 patient/caregiver has been: 247 a. Given the Fact Sheet for Patients and Parents/Caregivers, 248 b. Informed of alternatives to receiving remdesivir, and 249 c. Informed that remdesivir is an unapproved drug that is authorized 250 for use under EUA. 251 3. Adult and pediatric patients (>28 days old) must have an eGFR 252 determined and full-term neonates (≥7 days to ≤28 days old) must have 253 serum creatinine determined prior to remdesivir first administration. 254 4. Hepatic laboratory testing should be performed in all patients prior to 255 starting remdesivir and daily while receiving remdesivir. 256 5. Patients with known hypersensitivity to any ingredient of remdesivir must 257 not receive remdesivir. 258 The prescribing health care provider and/or the provider’s designee are/is 259 responsible for mandatory responses to requests from FDA for information 260 about adverse events and medication errors following receipt of 261 remdesivir. 262 6. The prescribing health care provider and/or the provider’s designee are/is 263 responsible for mandatory reporting of all medication errors and adverse 264 events (death, serious adverse events*) considered to be potentially 265 related to remdesivir occurring during remdesivir treatment within 7

7 266 calendar days from the onset of the event. The reports should include 267 unique identifiers and the words “Remdesivir under Emergency Use 268 Authorization (EUA)” in the description section of the report. 269 270 • Submit adverse event reports to FDA MedWatch using one of the 271 following methods: 272 . Complete and submit the report online: 273 www.fda.gov/medwatch/report.htm, or 274 . By using a postage-paid Form FDA 3500 (available at 275 http://www.fda.gov/downloads/AboutFDA/ReportsManualsForm 276 s/Forms/UCM163919.pdf) and returning by mail (MedWatch, 277 5600 Fishers Lane, Rockville, MD 20852-9787), or by fax (1- 278 800-FDA-0178), or 279 . Call 1-800-FDA-1088 to request a reporting form 280 . Submitted reports should include in the field name, “Describe 281 Event, Problem, or Product Use/Medication Error” a statement 282 “Remdesivir under Emergency Use Authorization (EUA).” 283 284 *Serious Adverse Events are defined as: 285 • death; 286 • a life-threatening adverse event; 287 • inpatient hospitalization or prolongation of existing hospitalization; 288 • a persistent or significant incapacity or substantial disruption of the 289 ability to conduct normal life functions; 290 • a congenital anomaly/birth defect; 291 • a medical or surgical intervention to prevent death, a life-threatening 292 event, hospitalization, disability, or congenital anomaly. 293 [see Adverse Reactions and Medication Errors Reporting Requirements and 294 Instructions (8)] 295 296 OTHER REPORTING REQUIREMENTS 297 In addition please provide a copy of all FDA MedWatch forms to: 298 Gilead Pharmacovigilance and Epidemiology 299 Fax: 1-650-522-5477 300 E-mail: [email protected] 301 302 APPROVED AVAILABLE ALTERNATIVES 303 304 There is no approved available alternative product. There are EUAs for other 305 COVID-19 treatments. Additional information on COVID-19 treatments can be 306 found at https://www.cdc.gov/coronavirus/2019-ncov/index.html. The health care 307 provider should visit https://clinicaltrials.gov/ to determine whether the patient 308 may be eligible for enrollment in a clinical trial. 309

8 310 AUTHORITY FOR ISSUANCE OF THE EUA 311 312 The Secretary of HHS has declared a public health emergency that justifies the 313 emergency use of remdesivir to treat COVID-19 caused by SARs-CoV-2. In 314 response, the FDA has issued an EUA for the unapproved product, remdesivir, 315 for the treatment of COVID-19.1 As a health care provider, you must comply with 316 the mandatory requirements of the EUA (see below). 317 318 FDA issued this EUA, requested by Gilead Sciences, Inc. and based on their 319 submitted data. 320 321 Although limited scientific information is available, based on the totality of the 322 scientific evidence available to date, it is reasonable to believe that remdesivir 323 may be effective for the treatment of COVID-19 in patients as specified in this 324 Fact Sheet. You may be contacted and asked to provide information to help with 325 the assessment of the use of the product during this emergency. 326 327 This EUA for remdesivir will end when the Secretary determines that the 328 circumstances justifying the EUA no longer exist or when there is a change in the 329 approval status of the product such that an EUA is no longer needed. 330 331 332

1 The health care 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.

9 333 FULL EUA PRESCRIBING INFORMATION 334 335 FULL EUA PRESCRIBING INFORMATION: 10 DRUG INTERACTIONS CONTENTS* 11 USE IN SPECIFIC POPULATIONS 11.1 Pregnancy 1 AUTHORIZED USE 11.2 Nursing Mothers 2 DOSAGE AND ADMINISTRATION 11.3 Pediatric Use 2.1 General Information 11.4 Geriatric Use 2.2 Adult Patients 11.5 Renal Impairment 2.3 Pediatric Patients 11.6 Hepatic Impairment 2.4 Pregnancy 12 OVERDOSAGE 2.5 Renal Impairment 2.6 Hepatic Impairment 13 PRODUCT DESCRIPTION 13.1 Physical Appearance 2.7 Adult Dose Preparation and Administration 13.2 Inactive Ingredients 2.8 Pediatric Dose Preparation and Administration 2.9 Storage of Prepared Dosages 14 CLINICAL PHARMACOLOGY 14.1 Mechanism of Action 3 DOSAGE FORMS AND STRENGTHS 14.2 Pharmacokinetics 4 CONTRAINDICATIONS 5 WARNINGS AND PRECAUTIONS 15 MICROBIOLOGY/RESISTANCE INFORMATION 5.1 Infusion-Related Reactions 16 NONCLINICAL TOXICOLOGY 5.2 Increased Risk of Transaminase Elevations 17 ANIMAL PHARMACOLOGIC AND EFFICACY 6 OVERALL SAFETY SUMMARY DATA 6.1 Clinical Trials Experience 18 CLINICAL TRIAL RESULTS AND SUPPORTING 6.2 Hepatic Adverse Reaction DATA FOR EUA 7 PATIENT MONITORING RECOMMENDATIONS 19 HOW SUPPLIED/STORAGE AND HANDLING 8 ADVERSE REACTIONS AND MEDICATION 20 PATIENT COUNSELING INFORMATION ERRORS REPORTING REQUIREMENTS AND 21 CONTACT INFORMATION INSTRUCTIONS *Sections or subsections omitted from the full 9 OTHER REPORTING REQUIREMENTS prescribing information are not listed. 336 337 338 1. AUTHORIZED USE 339 Remdesivir is authorized for use under an EUA for treatment of patients 340 hospitalized with suspected or laboratory confirmed SARS-CoV-2 infection and 341 severe disease. Severe disease is defined as patients with an oxygen saturation 342 (SpO2) ≤94% on room air or requiring supplemental oxygen or requiring 343 mechanical ventilation or requiring extracorporeal membrane oxygenation 344 (ECMO). Specifically, remdesivir is only authorized for hospitalized adult and 345 pediatric patients for whom use of an intravenous agent is clinically appropriate. 346 347 348 2. DOSAGE AND ADMINISTRATION 349 2.1 General Information 350 • The optimal dosing and duration of treatment is unknown. The suggested 351 dose and duration may be updated as data from clinical trials becomes 352 available. 353 • Adult and pediatric patients (>28 days old) must have an eGFR 354 determined and full-term neonates (≥7 days to ≤28 days old) must have 355 serum creatinine determined before dosing of remdesivir. 356 • Hepatic laboratory testing should be performed in all patients prior to 357 starting remdesivir and daily while receiving remdesivir. 358 • Remdesivir should be administered via intravenous (IV) infusion only. Do 359 not administer as an intramuscular (IM) injection. 360

10 361 2.2 Adult Patients 362 • The recommended dosage in adults requiring invasive mechanical 363 ventilation and/or ECMO is a single loading dose of remdesivir 200 mg on 364 Day 1 followed by once-daily maintenance doses of remdesivir 100 mg for 365 9 days. 366 • The recommended dosage in adults not requiring invasive mechanical 367 ventilation and/or ECMO is a single dose of remdesivir 200 mg on Day 1 368 followed by once-daily maintenance doses of remdesivir 100 mg for 4 369 days. If a patient does not demonstrate clinical improvement, treatment 370 may be extended for up to 5 additional days (i.e., up to a total of 10 days). 371 • Remdesivir is to be administered via intravenous infusion in a total volume 372 of up to 250 mL 0.9% saline over 30 to 120 minutes [see Dosage and 373 Administration (2.7)]. 374 375 All adult patients must have creatinine clearance determined before dosing [see 376 Dosage and Administration (2.5)]. 377 378 Hepatic laboratory testing should be performed in all patients prior to starting 379 remdesivir and daily while receiving remdesivir dosing [see Dosage and 380 Administration (2.6)]. 381 382 2.3 Pediatric Patients 383 Dosing in pediatric patients is based upon physiologically based (PBPK) 384 modeling and simulation of pharmacokinetic data from healthy adult 385 subjects. 386 387 The recommended pediatric dose for pediatric patients weighing between 3.5 kg 388 and <40 kg should be calculated using the mg/kg dose according to the patient’s 389 weight [see Dosage and Administration (2.8)]: 390 391 • For pediatric patients with body weight ≥40 kg requiring invasive 392 mechanical ventilation and/or ECMO, the adult dosage regimen of one 393 loading dose of remdesivir 200 mg IV (infused over 30 to 120 minutes) on 394 Day 1 followed by remdesivir 100 mg IV (infused over 30 to 120 minutes) 395 once daily for 9 days will be administered. 396 • For pediatric patients with body weight ≥40 kg not requiring invasive 397 mechanical ventilation and/or ECMO, the adult dosage regimen of one 398 loading dose of remdesivir 200 mg IV (infused over 30 to 120 minutes) on 399 Day 1 followed by remdesivir 100 mg IV (infused over 30 to 120 minutes) 400 once daily for 4 days (days 2 through 5) will be administered. If a patient 401 does not demonstrate clinical improvement, treatment may be extended 402 for up to 5 additional days (i.e., up to a total of 10 days). Use of the adult 403 dose in these pediatric patients is expected to maintain exposures of both 404 remdesivir and the nucleoside analog GS-441524 generally within the 405 expected adult steady-state exposure range following administration of the

11 406 adult therapeutic dosage regimen in healthy volunteers (N=20 Study GS- 407 US-399-5505). 408 • For pediatric patients with body weight between 3.5 kg and <40 kg, use 409 remdesivir for injection, 100 mg, lyophilized powder only. Administer a 410 body weight-based dosing regimen of one loading dose of remdesivir 5 411 mg/kg IV (infused over 30 to 120 min) on Day 1 followed by remdesivir 2.5 412 mg/kg IV (infused over 30 to 120 min) once daily for 9 days (for pediatric 413 patients requiring invasive mechanical ventilation and/or ECMO, days 2 414 through 10) or for 4 days (for pediatric patients not requiring invasive 415 mechanical ventilation and/or ECMO, days 2 through 5). If a patient does 416 not demonstrate clinical improvement, treatment may be extended for up 417 to 5 additional days (i.e., up to a total of 10 days). Use of this weight- 418 based dosing regimen is expected to maintain remdesivir exposure that is 419 comparable to that observed in adults while limiting the exposure of the 420 nucleoside analog GS-441524 in very young children. 421 422 Pediatric patients (>28 days old) must have an eGFR determined and full-term 423 neonates (≥7 days to ≤28 days old) must have serum creatinine determined 424 before dosing [see Dosage and Administration (2.5)]. 425 426 Hepatic laboratory testing should be performed in all patients prior to starting 427 remdesivir and daily while receiving remdesivir dosing [see Dosage and 428 Administration (2.6)]. 429 430 2.4 Pregnancy 431 Remdesivir should be used during pregnancy only if the potential benefit justifies 432 the potential risk for the mother and the fetus. 433 434 2.5 Renal Impairment 435 The pharmacokinetics of remdesivir have not been evaluated in patients with 436 renal impairment. Adult and pediatric patients (>28 days old) must have an eGFR 437 determined and full-term neonates (≥7 days to ≤28 days old) must have serum 438 creatinine determined before dosing. 439 440 Because the excipient sulfobutylether-β-cyclodextrin sodium salt (SBECD) is 441 renally cleared and accumulates in patients with decreased renal function, 442 administration of drugs formulated with SBECD (such as remdesivir) is not 443 recommended in adults and pediatric patients (>28 days old) with eGFR less 444 than 30 mL per minute or in full-term neonates (≥7 days and ≤28 days old) with 445 serum creatinine clearance ≥1 mg/dL unless the potential benefit outweighs the 446 potential risk. 447 448 2.6 Hepatic Impairment 449 The pharmacokinetics of remdesivir have not been evaluated in patients with 450 hepatic impairment. It is not known if dosage adjustment is needed in patients 451 with hepatic impairment and remdesivir should only be used in patients with

12 452 hepatic impairment if the potential benefit outweighs the potential risk [see 453 Warnings and Precautions (5.2)]. 454 455 Hepatic laboratory testing should be performed in all patients prior to starting 456 remdesivir and daily while receiving remdesivir. 457 458 2.7 Adult Dose Preparation and Administration 459 460 Remdesivir for Injection, 100 mg, Lyophilized Powder 461 462 Reconstitution Instructions 463 464 Remove the required number of single-dose vial(s) from storage. For each vial: 465 • Aseptically reconstitute remdesivir lyophilized powder by addition of 19 mL 466 of Sterile Water for Injection using a suitably sized syringe and needle per 467 vial. 468 • Discard the vial if a vacuum does not pull the Sterile Water for Injection 469 into the vial. 470 • Immediately shake the vial for 30 seconds. 471 • Allow the contents of the vial to settle for 2 to 3 minutes. A clear solution 472 should result. 473 • If the contents of the vial are not completely dissolved, shake the vial 474 again for 30 seconds and allow the contents to settle for 2 to 3 minutes. 475 Repeat this procedure as necessary until the contents of the vial are 476 completely dissolved. 477 • Following reconstitution, each vial contains 100 mg/20 mL (5 mg/mL) of 478 remdesivir solution. 479 • Parenteral drug products should be inspected visually for particulate 480 matter and discoloration prior to administration, whenever solution and 481 container permit. 482 • After reconstitution, the total storage time before administration should not 483 exceed 4 hours at room temperature or 24 hours at refrigerated 484 temperature (2°C to 8°C [36°F to 46°F]). 485 486 Dilution Instructions 487 488 Care should be taken during admixture to prevent inadvertent microbial 489 contamination. As there is no preservative or bacteriostatic agent present in this 490 product, aseptic technique must be used in preparation of the final parenteral 491 solution. It is always recommended to administer IV medication immediately after 492 preparation when possible. 493 • Using Table 1, determine the volume of 0.9% saline to withdraw from the 494 infusion bag.

13 495 Table 1: Recommended Dilution Instructions— Remdesivir for Injection 496 Lyophilized Powder in Adults and Pediatric Patients Weighing 497 ≥40 kg Volume of saline to be withdrawn Required volume 0.9% saline and discarded of reconstituted Remdesivir infusion bag from 0.9% saline remdesivir for dose volume to be used infusion bag injection 200 mg 250 mL 40 mL 2 × 20 mL (2 vials) 100 mL 40 mL 2 × 20 mL 100 mg 250 mL 20 mL 20 mL (1 vial) 100 mL 20 mL 20 mL

498 • Withdraw the required volume of saline from the bag using an 499 appropriately sized syringe and needle. Discard the saline that was 500 withdrawn from the bag. 501 • Withdraw the required volume of reconstituted remdesivir for injection from 502 the remdesivir vial using an appropriately sized syringe per Table 1. 503 Discard any unused portion remaining in the remdesivir vial. 504 • Transfer the required volume of reconstituted remdesivir for injection to 505 the selected infusion bag. 506 • Gently invert the bag 20 times to mix the solution in the bag. Do not 507 shake. 508 • The prepared diluted solution is stable for 4 hours at room temperature 509 (20°C to 25°C [68°F to 77°F]) or 24 hours in the refrigerator at 2°C to 8°C 510 (36°F to 46°F). 511 512 Administration Instructions 513 514 The prepared diluted solution should not be administered simultaneously with 515 any other medication. The compatibility of remdesivir injection with IV solutions 516 and medications other than saline is not known. 517 518 Administer the diluted solution with the infusion rate described in Table 2. 519

14 520 Table 2: Recommended Rate of Infusion — Diluted Remdesivir for 521 Injection Lyophilized Powder in Adults and Pediatric Patients 522 Weighing ≥40 kg Infusion bag volume Infusion time Rate of infusion 30 min 8.33 mL/min 250 mL 60 min 4.17 mL/min 120 min 2.08 mL/min 30 min 3.33 mL/min 100 mL 60 min 1.67 mL/min 120 min 0.83 mL/min 523 524 Remdesivir Injection, 5 mg/mL, Solution 525 526 Dilution Instructions 527 528 Care should be taken during admixture to prevent inadvertent microbial 529 contamination. As there is no preservative or bacteriostatic agent present in this 530 product, aseptic technique must be used in preparation of the final parenteral 531 solution. It is always recommended to administer IV medication immediately after 532 preparation when possible. 533 534 • Remove the required number of single-dose vial(s) from storage. For each 535 vial: 536 • Equilibrate to room temperature (20°C to 25°C [68°F to 77°F]). 537 Sealed vials can be stored up to 12 hours at room temperature 538 prior to dilution. 539 • Inspect the vial to ensure the container closure is free from defects 540 and the solution is free of particulate matter. 541 • Using Table 3, determine the volume of 0.9% saline to withdraw from the 542 infusion bag.

15 543 Table 3: Recommended Remdesivir Solution Dilution Instructions in 544 Adults and Pediatric Patients Weighing ≥40 kg Volume of saline to be withdrawn 0.9% saline and discarded Required volume Remdesivir infusion bag from 0.9% saline of remdesivir dose volume to be used infusion bag injection solution 200 mg 40 mL 2 × 20 mL (2 vials) 250 mL 100 mg 20 mL 20 mL (1 vial)

545 • Withdraw the required volume of saline from the bag using an 546 appropriately sized syringe and needle. Discard the saline that was 547 withdrawn from the bag. 548 • Withdraw the required volume of remdesivir injection solution from the 549 remdesivir vial using an appropriately sized syringe per Table 3. 550 • Pull the syringe plunger rod back to fill the syringe with 551 approximately 10 mL of air. 552 • Inject the air into the remdesivir injection vial above the level of the 553 solution. 554 • Invert the vial and withdraw the required volume of remdesivir 555 injection solution into the syringe. The last 5 mL of solution requires 556 more force to withdraw. 557 • Discard any unused solution remaining in the remdesivir vial. 558 • Transfer the required volume of remdesivir injection solution to the 559 infusion bag. 560 • Gently invert the bag 20 times to mix the solution in the bag. Do not 561 shake. 562 • The prepared diluted solution is stable for 4 hours at room temperature 563 (20°C to 25°C [68°F to 77°F]) or 24 hours in the refrigerator at 2°C to 8°C 564 (36°F to 46°F). 565 566 Administration Instructions 567 568 The prepared diluted solution should not be administered simultaneously with 569 any other medication. The compatibility of remdesivir injection with IV solutions 570 and medications other than saline is not known. 571 572 • Administer the diluted solution with the infusion rate described in Table 4.

16 573 Table 4: Recommended Rate of Infusion for Diluted Remdesivir 574 Solution in Adults and Pediatric Patients Weighing ≥40 kg

Infusion bag volume Infusion time Rate of infusion 30 min 8.33 mL/min 250 mL 60 min 4.17 mL/min 120 min 2.08 mL/min 575 576 2.8 Pediatric Dose Preparation and Administration 577 578 Remdesivir for Injection, 100 mg, Lyophilized Powder 579 580 For pediatric patients with body weight between 3.5 kg and <40 kg, use 581 remdesivir for injection, 100 mg, lyophilized powder only. 582 583 Reconstitution Instructions 584 585 Remove the required number of single-dose vial(s) from storage. For each vial: 586 • Aseptically reconstitute remdesivir lyophilized powder by addition of 19 mL 587 of Sterile Water for Injection using a suitably sized syringe and needle per 588 vial. 589 • Discard the vial if a vacuum does not pull the Sterile Water for 590 Injection into the vial. 591 • Immediately shake the vial for 30 seconds. 592 • Allow the contents of the vial to settle for 2 to 3 minutes. A clear solution 593 should result. 594 • If the contents of the vial are not completely dissolved, shake the vial 595 again for 30 seconds and allow the contents to settle for 2 to 3 minutes. 596 Repeat this procedure as necessary until the contents of the vial are 597 completely dissolved. 598 • Following reconstitution, each vial contains 100 mg/20 mL (5 mg/mL) of 599 remdesivir solution. 600 • Parenteral drug products should be inspected visually for particulate 601 matter and discoloration prior to administration, whenever solution and 602 container permit. 603 • After reconstitution, the total storage time before administration should not 604 exceed 4 hours at room temperature or 24 hours at refrigerated 605 temperature (2°C to 8°C [36°F to 46°F]). 606 607 Dilution Instructions 608 609 Care should be taken during admixture to prevent inadvertent microbial 610 contamination. As there is no preservative or bacteriostatic agent present in this 611 product, aseptic technique must be used in preparation of the final parenteral

17 612 solution. It is always recommended to administer IV medication immediately after 613 preparation when possible. 614 615 • Using Table 5 and Table 6, determine the volume of 0.9% saline to 616 withdraw from the infusion bag. Table 5 and Table 6 include the volume 617 requirements for preparing pediatric weight-based dosing regimens at 5 618 mg/kg and 2.5 mg/kg, respectively.

619 Table 5: Recommended Remdesivir Loading Dose Dilution Instructions 620 for Pediatric Patients Weighing 3.5 kg to <40 kg Pediatric loading 0.9% Volume of dose for saline saline to be Required body infusion withdrawn and volume of weight <40 bag discarded from reconstituted Body kg volume to 0.9% saline remdesivir for weight 5 mg/kg be used infusion bag injection (kg) (mg) (mL) (mL) (mL) 3.5 17.5 3.5 3.5 4 20 25 4 4 5 25 5 5 7.5 37.5 7.5 7.5 50 10 50 10 10 15 75 15 15 20 100 20 20 100 25 125a 25 (20+5) 25 (20+5) 30 150a 30 (20+10) 30 (20+10) 35 175a 250 35 (20+15) 35 (20+15)

621 a. These doses require the use of 2 vials of remdesivir for Injection.

622 623

18 624 Table 6: Recommended Remdesivir Maintenance Dose Dilution 625 Instructions for Pediatric Patients Weighing 3.5 kg to <40 kg Pediatric 0.9% Volume of maintenance saline saline to be Required dose for infusion withdrawn and volume of body weight bag discarded from reconstituted Body <40 kg volume to 0.9% saline remdesivir for weight 2.5 mg/kg be used infusion bag injection (kg) (mg) (mL) (mL) (mL) 3.5 8.8 0 1.8

4 10 25 0 2

5 12.5 2.5 2.5

7.5 18.8 3.8 3.8

10 25 5 5 50 15 37.5 7.5 7.5

20 50 10 10

25 62.5 12.5 12.5

30 75 100 15 15

35 87.5 17.5 17.5

626 • Withdraw the required volume of saline from the bag using an 627 appropriately sized syringe and needle. Discard the saline that was 628 withdrawn from the bag. 629 • Withdraw the required volume of reconstituted remdesivir for injection from 630 the remdesivir vial using an appropriately sized syringe per Table 5 or 6. 631 Discard any unused portion remaining in the remdesivir vial. 632 • Transfer the required volume of reconstituted remdesivir for injection to 633 the selected infusion bag. 634 • Gently invert the bag 20 times to mix the solution in the bag. Do not 635 shake. 636 • The prepared diluted solution is stable for 4 hours at room temperature 637 (20°C to 25°C [68°F to 77°F]) or 24 hours in the refrigerator at 2°C to 8°C 638 (36°F to 46°F) (including any time before dilution into intravenous infusion 639 fluids). 640 641

19 642 Administration Instructions 643 644 The prepared diluted solution should not be administered simultaneously with 645 any other medication. The compatibility of remdesivir injection with IV solutions 646 and medications other than saline is not known. 647 648 Administer the diluted solution with the infusion rate described in Table 7.

649 Table 7: Recommended Rate of Infusion for Pediatric Patients 650 Weighing 3.5 kg to <40 kg

Infusion bag volume Infusion time Rate of infusiona 30 min 3.33 mL/min 100 mL 60 min 1.67 mL/min 120 min 0.83 mL/min 30 min 1.67 mL/min 50 mL 60 min 0.83 mL/min 120 min 0.42 mL/min 30 min 0.83 mL/min 25 mL 60 min 0.42 mL/min 120 min 0.21 mL/min 651 a. Note: Rate of infusion may be adjusted based on total volume to be infused. 652 653 2.9 Storage of Prepared Dosages 654 655 Lyophilized Powder 656 657 After reconstitution, vials can be stored up to 4 hours at room temperature (20°C 658 to 25°C [68°F to 77°F]) prior to administration or 24 hours at refrigerated 659 temperature (2°C to 8°C [36°F to 46°F]). Dilute within the same day as 660 administration. 661 662 Injection Solution 663 Prior to dilution, equilibrate remdesivir injection to room temperature (20°C to 664 25°C [68°F to 77°F]). Sealed vials can be stored up to 12 hours at room 665 temperature prior to dilution. 666 667 Diluted Infusion Solution 668 Store diluted remdesivir solution for infusion up to 4 hours at room temperature 669 (20°C to 25°C [68°F to 77°F]) or 24 hours at refrigerated temperature (2°C to 8°C 670 [36°F to 46°F]).

20 671 672 IMPORTANT: 673 This product contains no preservative. Any unused portion of a single-dose 674 remdesivir vial should be discarded after a diluted solution is prepared. Maintain 675 adequate records showing receipt, use, and disposition of remdesivir. For 676 unused intact vials, maintain adequate records showing disposition of remdesivir; 677 do not discard unused intact vials. 678 679 3. DOSAGE FORMS AND STRENGTHS 680 681 • Remdesivir for injection, 100 mg: Each single-dose vial of remdesivir for 682 injection,100 mg, contains a sterile, preservative-free white to off-white to 683 yellow lyophilized powder that is to be reconstituted with 19 mL of Sterile 684 Water for Injection and diluted into 0.9% saline prior to administration by 685 intravenous infusion. Following reconstitution, each vial contains 5 mg/mL 686 remdesivir reconcentrated solution with sufficient volume to allow withdrawal 687 of 20 mL of 5 mg/mL solution containing 100 mg of remdesivir. 688 689 • Remdesivir injection, 5 mg/mL: Each single-dose vial of remdesivir injection 690 contains 5 mg/mL of remdesivir as a clear, colorless to yellow, aqueous- 691 based concentrated solution. Each vial contains sufficient volume to allow 692 withdrawal of 20 mL of 5 mg/mL solution containing 100 mg of remdesivir. 693 694 4. CONTRAINDICATIONS 695 Remdesivir is contraindicated in patients with known hypersensitivity to any 696 ingredient of remdesivir [see Product Description (13)]. 697 698 5. WARNINGS AND PRECAUTIONS 699 There are limited clinical data available for remdesivir. Serious and unexpected 700 adverse events may occur that have not been previously reported with remdesivir 701 use. 702 703 5.1 Infusion-Related Reactions 704 Infusion-related reactions have been observed during, and/or been temporally 705 associated with, administration of remdesivir. Signs and symptoms may include 706 hypotension, nausea, vomiting, diaphoresis, and shivering. If signs and 707 symptoms of a clinically significant infusion reaction occur, immediately 708 discontinue administration of remdesivir and initiate appropriate treatment. The 709 use of remdesivir is contraindicated in patients with known hypersensitivity to 710 remdesivir.

21 711 5.2 Increased Risk of Transaminase Elevations 712 713 Transaminase elevations have been observed in the remdesivir clinical 714 development program, including in healthy volunteers and patients with COVID- 715 19. In healthy volunteers who received up to 150 mg daily for 14 days, alanine 716 aminotransferase (ALT) elevations were observed in the majority of patients, 717 including elevations to up to 10 times baseline values in one subject without 718 evidence of clinical hepatitis; no ≥ Grade 3 adverse events were observed. 719 Transaminase elevations have also been reported in patients with COVID-19 720 who received remdesivir, including one patient with ALT elevation up to 20 times 721 the upper limit of normal. As transaminase elevations have been reported as a 722 component of COVID-19 in some patients, discerning the contribution of 723 remdesivir to transaminase elevations in this patient population is challenging. 724 725 Hepatic laboratory testing should be performed in all patients prior to starting 726 remdesivir and daily while receiving remdesivir. 727 • Remdesivir should not be initiated in patients with ALT ≥ 5 times the upper 728 limit of normal at baseline 729 • Remdesivir should be discontinued in patients who develop: 730 o ALT ≥ 5 times the upper limit of normal during treatment with 731 remdesivir. Remdesivir may be restarted when ALT is < 5 times the 732 upper limit of normal. 733 OR 734 o ALT elevation accompanied by signs or symptoms of liver 735 inflammation or increasing conjugated bilirubin, alkaline 736 phosphatase, or INR 737 738 Completion of FDA MedWatch Form to report all medication errors and 739 adverse events occurring during remdesivir treatment is mandatory. Please 740 see the ADVERSE REACTIONS AND MEDICATION ERRORS REPORTING 741 REQUIREMENTS AND INSTRUCTIONS section below for details on FDA 742 MedWatch reporting. 743 744 6. OVERALL SAFETY SUMMARY 745 746 In healthy subjects and hospitalized patients with PCR-confirmed SARS-CoV-2 747 infection, graded elevations in ALT and AST have been observed with a loading 748 dose of remdesivir 200 mg administered intravenously on Day 1 followed by 100 749 mg administered intravenously once daily for up to 9 days. The mechanism of 750 these elevations is unknown. 751 752 Patients should have appropriate clinical and laboratory monitoring to aid in early 753 detection of any potential adverse events. The decision to continue or 754 discontinue remdesivir after development of an adverse event should be made 755 based on the clinical risk benefit assessment for the individual. 756

22 757 6.1 Clinical Trials Experience 758 In a randomized, open-label clinical trial (Study GS-US-540-5773) of remdesivir 759 in 397 subjects with severe COVID-19 treated with remdesivir for 5 (n=200) or 10 760 days (n=197), adverse events were reported in 71% and 74% of subjects, 761 respectively, serious adverse events were reported in 21% and 35% of subjects, 762 respectively, and Grade ≥3 adverse events were reported in 31% and 43% of 763 subjects, respectively. Nine (5%) subjects in the 5-day group and 20 (10%) 764 subjects in the 10-day group discontinued treatment due to an adverse event. All- 765 cause mortality at Day 28 was 10% vs 13% in the 5- and 10-day treatment 766 groups, respectively. 767 768 6.2 Hepatic Adverse Reactions 769 770 Clinical Trials Experience 771 772 Experience in Healthy Volunteers 773 Grade 1 and 2 transaminase elevations were observed in healthy volunteers in 774 Study GS-US-399-5505 (200 mg followed by 100 mg dosing for 5–10 days) and 775 Study GS-US-399-1954 (150 mg daily for 7 or 14 days), which resolved after 776 discontinuation of remdesivir. 777 778 Experience in Patients with COVID-19 779 780 Grade ≥3 hepatic laboratory abnormalities reported in Study GS-US-540-5773 of 781 remdesivir in 397 subjects with severe COVID-19 treated with remdesivir for 5 782 (n=200) or 10 days (n=197) are shown in Table 8. 783 784 Table 8: Hepatic Laboratory Abnormalities—Study GS-US-540-5773 Remdesivir Remdesivir for n/N (%) Total for 5 Days 10 Days Grade 3 8/194 (4) 11/191 (6) 19/385 (5) ALT Grade 4 4/194 (2) 5/191 (3) 9/385 (2) Grade 3 11/194 (6) 7/190 (4) 18/384 (5) AST Grade 4 3/194 (2) 4/190 (2) 7/384 (2) Total Grade 3 1/193 (1) 3/190 (2) 4/383 (1) Bilirubin Grade 4 0 1/190 (1) 1/383 (<1) 785 786 Experience in Patients with Ebola Virus Disease 787 In the PALM study, 175 subjects with Ebola virus disease were randomized to 788 receive remdesivir. No SAEs of transaminase elevations or hepatic events were 789 reported. 790

23 791 Twenty subjects received remdesivir in a double-blinded, randomized, viral 792 persistence study in the semen of Ebola survivors. Preliminary results indicated 793 there were no SAEs for transaminase elevations. 794 795 Compassionate Use Experience 796 797 Experience in Patients with COVID-19 798 In the compassionate use program in patients with severe or critical illness with 799 COVID-19, liver function test abnormalities were reported in 11.7% (19/163) of 800 patients. Time to onset from first dose ranged from 1-16 days. Four of these 801 patients discontinued remdesivir treatment with elevated transaminases 802 occurring on Day 5 of remdesivir treatment as per protocol. 803 804 Seven cases of serious liver-related laboratory abnormality were identified. There 805 was 1 serious adverse event (SAE) of blood bilirubin increased in a critically ill 806 patient with septic shock and multiorgan failure. None of the other cases had 807 reported adverse events suggestive of hyperbilirubinemia or symptoms of 808 hepatitis. 809 810 7. PATIENT MONITORING RECOMMENDATIONS 811 Given the limited experience with remdesivir at the recommended dose and 812 duration, patients should have appropriate clinical and laboratory monitoring to 813 aid in early detection of any potential adverse events while receiving remdesivir. 814 The following laboratory tests should be performed daily while receiving 815 remdesivir: serum chemistries, hematology, ALT, AST, bilirubin, and alkaline 816 phosphatase; renal function tests (creatinine and creatinine clearance). 817 Additionally, completion of FDA MedWatch Form to report all medication 818 errors and serious adverse events is mandatory. 819 820 For mandatory reporting requirements, please see “MANDATORY 821 REQUIREMENTS FOR REMDESIVIR ADMINISTRATION UNDER 822 EMERGENCY USE AUTHORIZATION” above. 823 824 8. ADVERSE REACTIONS AND MEDICATION ERRORS REPORTING 825 REQUIREMENTS AND INSTRUCTIONS 826 See Warnings and Precautions for more information. 827 828 The prescribing health care provider and/or the provider’s designee are/is 829 responsible for the mandatory reporting of all medication errors and the following 830 selected adverse events occurring during remdesivir use and considered to be 831 potentially attributable to remdesivir. These adverse events must be reported 832 within 7 calendar days from the onset of the event: 833 834 • Deaths 835 • Serious Adverse Events 836

24 837 Serious Adverse Events are defined as: 838 • death; 839 • a life-threatening adverse event; 840 • inpatient hospitalization or prolongation of existing hospitalization; 841 • a persistent or significant incapacity or substantial disruption of the 842 ability to conduct normal life functions; 843 • a congenital anomaly/birth defect; 844 • a medical or surgical intervention to prevent death, a life-threatening 845 event, hospitalization, disability, or congenital anomaly. 846 847 If a serious and unexpected adverse event occurs and appears to be associated 848 with the use of remdesivir, the prescribing health care provider and/or the 849 provider’s designee should complete and submit a MedWatch form to FDA using 850 one of the following methods: 851 • Complete and submit the report online: 852 www.fda.gov/medwatch/report.htm, or 853 • Use a postage-paid Form FDA 3500 (available at 854 http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/For 855 ms/UCM163919.pdf) and returning by mail (MedWatch, 5600 Fishers 856 Lane, Rockville, MD 20852-9787), or by fax (1-800-FDA-0178), or 857 • Call 1-800-FDA-1088 to request a reporting form 858 859 IMPORTANT: When reporting adverse events or medication errors to 860 MedWatch, please complete the entire form with detailed information. It is 861 important that the information reported to FDA be as detailed and complete 862 as possible. Information to include: 863 • Patient Demographics (e.g., Remdesivir Request number, patient initials, 864 date of birth) 865 • Pertinent medical history 866 • Pertinent details regarding admission and course of illness 867 • Concomitant medications 868 • Timing of adverse event(s) in relationship to administration of Remdesivir 869 • Pertinent laboratory and virology information 870 • Outcome of the event and any additional follow-up information if it is 871 available at the time of the MedWatch report. Subsequent reporting of 872 follow-up information should be completed if additional details become 873 available (use the same Remdesivir Request number when completing the 874 report).

875 The following steps are highlighted to provide the necessary information for 876 safety tracking:

877 1. In section A, box 1, provide the Remdesivir Request number and the 878 patient’s initials in the Patient Identifier 879 2. In section A, box 2, provide the patient’s date of birth 880 3. In section B, box 5, description of the event:

25 881 a. Write “Remdesivir EUA” as the first line 882 b. Provide a detailed report of medication error and/or adverse event. 883 It is important to provide detailed information regarding the patient 884 and adverse event/medication error for ongoing safety evaluation of 885 this unapproved drug. Please see information to include listed 886 above. 887 4. In section G, box 1, name and address: 888 a. Provide the name and contact information of the prescribing health 889 care provider or institutional designee who is responsible for the 890 report 891 b. Provide the address of the treating institution (NOT the health care 892 provider’s office address). 893 894 9. OTHER REPORTING REQUIREMENTS 895 In addition please provide a copy of all FDA MedWatch forms to: 896 Gilead Pharmacovigilance and Epidemiology 897 Fax: 1-650-522-5477 898 E-mail: [email protected] 899 900 10. DRUG INTERACTIONS 901 Drug-drug interaction trials of remdesivir and other concomitant medications 902 have not been conducted in humans. In vitro, remdesivir is a substrate for drug 903 metabolizing enzymes CYP2C8, CYP2D6, and CYP3A4, and is a substrate for 904 Organic Anion Transporting Polypeptides 1B1 (OAPT1B1) and P-glycoprotein (P- 905 gp) transporters. In vitro, remdesivir is an inhibitor of CYP3A4, OATP1B1, 906 OATP1B3, BSEP, MRP4, and NTCP. The clinical relevance of these in vitro 907 assessments has not been established. 908 909 11. USE IN SPECIFIC POPULATIONS 910 911 11.1 Pregnancy 912 Risk Summary 913 No adequate and well-controlled studies of remdesivir use in pregnant women 914 have been conducted. Remdesivir should be used during pregnancy only if the 915 potential benefit justifies the potential risk for the mother and the fetus. 916 In nonclinical reproductive toxicity studies, remdesivir demonstrated no adverse 917 effect on embryofetal development when administered to pregnant animals at 918 systemic exposures (AUC) of the predominant circulating metabolite of 919 remdesivir (GS-441524) that were 4 times (rats and rabbits) the exposure in 920 humans at the recommended human dose (RHD) (see Data). 921 Animal Data 922 Remdesivir was administered via intravenous injection to pregnant rats and 923 rabbits (up to 20 mg/kg/day) on Gestation Days 6 through 17, and 7 through 20, 924 respectively, and also to rats from Gestation Day 6 to Lactation/Post-partum Day 925 20. No adverse effects on embryo-fetal (rats and rabbits) or pre/postnatal (rats)

26 926 development were observed in rats and rabbits at nontoxic doses in pregnant 927 animals. During organogenesis, exposures to the predominant circulating 928 metabolite (GS-441524) were 4 (rats and rabbits) times higher than the exposure 929 in humans at the RHD. In a pre/postnatal development study, exposures to the 930 predominant circulating metabolite of remdesivir (GS-441524) were similar to the 931 human exposures at the RHD. 932 933 11.2 Nursing Mothers 934 Risk Summary 935 There is no information regarding the presence of remdesivir in human milk, the 936 effects on the breastfed infant, or the effects on milk production. In animal 937 studies, remdesivir and metabolites have been detected in the nursing pups of 938 mothers given remdesivir, likely due to the presence of remdesivir in milk. 939 Because of the potential for viral transmission to SARS-CoV-2-negative infants 940 and adverse reactions from the drug in breastfeeding infants, the developmental 941 and health benefits of breastfeeding should be considered along with the 942 mother’s clinical need for remdesivir and any potential adverse effects on the 943 breastfed child from remdesivir or from the underlying maternal condition. 944 945 Animal Data 946 Remdesivir and its metabolites were detected in the plasma of nursing rat pups, 947 likely due to the presence of remdesivir and/or its metabolites in milk, following 948 daily intravenous administration of remdesivir to pregnant mothers from 949 Gestation Day 6 to Lactation Day 20. Exposures in nursing pups were 950 approximately 1% that of maternal exposure on lactation day 10. 951 952 11.3 Pediatric Use 953 The safety and effectiveness of remdesivir for treatment of COVID-19 have not 954 been assessed in pediatric patients. Dosing instructions for pediatric patients 955 were derived based on pharmacokinetic data from adult healthy volunteers and 956 in vitro data for remdesivir and other similar compounds, as part of the PBPK 957 modeling and simulation approach which accounts for age-dependent changes in 958 metabolism, distribution, and elimination of remdesivir. 959 960 For pediatric patients with body weight between 3.5 kg to <40 kg, use remdesivir 961 for injection, 100 mg, lyophilized powder only [see Dosage and Administration 962 (2.3 and 2.8)]. 963 964 Pediatric patients (>28 days) must have creatinine clearance determined and full- 965 term neonates (≥7 days to ≤28 days) must have serum creatinine determined 966 before dosing. Pediatric patients should be monitored for renal function and 967 consideration given for stopping therapy in the setting of substantial decline. The 968 use of remdesivir is not recommended in pediatric patients (>28 days old) with 969 eGFR <30 mL/min and in full-term neonates (≥7 days and ≤28 days old) with

27 970 serum creatinine clearance ≥1 mg/dL unless the potential benefit outweighs the 971 potential risk. 972 973 Because the excipient sulfobutylether-β-cyclodextrin sodium salt (SBECD) is 974 renally cleared and accumulates in patients with decreased renal function, 975 administration of drugs formulated with SBECD (such as remdesivir) is not 976 recommended in adults and pediatric patients (>28 days old) with eGFR less 977 than 30 mL per minute or in full-term neonates (≥7 days and ≤28 days old) with 978 serum creatinine clearance ≥1 mg/dL unless the potential benefit outweighs the 979 potential risk. 980 981 11.4 Geriatric Use 982 The pharmacokinetics of remdesivir have not been evaluated in patients >65 983 years of age. In general, appropriate caution should be exercised in the 984 administration of remdesivir and monitoring of elderly patients, reflecting the 985 greater frequency of decreased hepatic, renal, or cardiac function, and of 986 concomitant disease or other drug therapy. 987 988 11.5 Renal Impairment 989 The pharmacokinetics of remdesivir have not been evaluated in patients with 990 renal impairment. Adult and pediatric patients (>28 days old) must have 991 creatinine clearance determined and full-term neonates (≥7 days to ≤28 days old) 992 must have serum creatinine determined before dosing. Remdesivir is not 993 recommended in adults and pediatric patients (>28 days old) with eGFR less 994 than 30 mL per minute or in full-term neonates (≥7 days and ≤28 days old) with 995 serum creatinine clearance ≥1 mg/dL unless the potential benefit outweighs the 996 potential risk. 997 998 11.6 Hepatic Impairment 999 The pharmacokinetics of remdesivir have not been evaluated in patients with 1000 hepatic impairment. It is not known if dosage adjustment is needed in patients 1001 with hepatic impairment and remdesivir should only be used in patients with 1002 hepatic impairment if the potential benefit outweighs the potential risk [see 1003 Warnings and Precautions (5.2)]. 1004 1005 Hepatic laboratory testing should be performed in all patients prior to starting 1006 remdesivir and daily while receiving remdesivir. 1007 1008 12. OVERDOSAGE 1009 There is no human experience of acute overdosage with remdesivir. Treatment 1010 of overdose with remdesivir should consist of general supportive measures 1011 including monitoring of vital signs and observation of the clinical status of the 1012 patient. There is no specific antidote for overdose with remdesivir. 1013 1014 13. PRODUCT DESCRIPTION 1015 Remdesivir is a nucleoside ribonucleic acid (RNA) polymerase inhibitor.

28 1016 1017 The chemical name for remdesivir is 2-ethylbutyl N-{(S)-[2-C-(4- 1018 aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-2,5-anhydro-d-altrononitril-6-O- 1019 yl]phenoxyphosphoryl}-L-alaninate. It has a molecular formula of C27H35N6O8P 1020 and a molecular weight of 602.6 g/mol. Remdesivir has the following structural 1021 formula:

1022 1023 13.1 Physical Appearance

1024 Lyophilized Powder

1025 Remdesivir for injection, 100 mg, is a sterile, preservative-free lyophilized powder 1026 that is to be reconstituted with 19 mL of Sterile Water for Injection and diluted into 1027 0.9% saline prior to administration by intravenous infusion. Remdesivir for 1028 injection, 100 mg, is supplied in a single-dose clear glass vial.

1029 The appearance of the lyophilized powder is white to off-white to yellow.

1030 Injection Solution

1031 Remdesivir injection, 5 mg/mL, is a sterile, preservative-free, clear, colorless to 1032 yellow, aqueous-based concentrated solution that is to be diluted into 0.9% 1033 saline prior to administration by intravenous infusion remdesivir injection, 5 1034 mg/mL, is supplied in a single-dose clear glass vial.

1035 13.2 Inactive Ingredients 1036 The inactive ingredients are sulfobutylether-β-cyclodextrin sodium salt (SBECD), 1037 Water for Injection, USP, and may include hydrochloric acid and/or sodium 1038 hydroxide for pH adjustment. Remdesivir for injection, 100 mg, contains 3 g 1039 SBECD and remdesivir injection, 5 mg/mL contains 6 g SBECD. 1040

29 1041 14. CLINICAL PHARMACOLOGY 1042 1043 14.1 Mechanism of Action 1044 Remdesivir is an adenosine nucleotide prodrug that distributes into cells where it 1045 is metabolized to form the pharmacologically active nucleoside triphosphate 1046 metabolite. Metabolism of remdesivir to remdesivir triphosphate has been 1047 demonstrated in multiple cell types. Remdesivir triphosphate acts as an analog of 1048 adenosine triphosphate (ATP) and competes with the natural ATP substrate for 1049 incorporation into nascent RNA chains by the SARS-CoV-2 RNA-dependent 1050 RNA polymerase, which results in delayed chain termination during replication of 1051 the viral RNA. Remdesivir triphosphate is a weak inhibitor of mammalian DNA 1052 and RNA polymerases with low potential for mitochondrial toxicity. 1053 1054 14.2 Pharmacokinetics 1055 The pharmacokinetics (PK) of remdesivir have been evaluated in adults in 1056 several Phase 1 trials. 1057 • Following single-dose, 2-hour IV administration of remdesivir solution 1058 formulation at doses ranging from 3 to 225 mg, remdesivir exhibited a linear 1059 PK profile. 1060 • Following single-dose, 2-hour IV administration of remdesivir at doses of 75 1061 and 150 mg, both the lyophilized and solution formulations provided 1062 comparable PK parameters (AUCinf, AUClast, and Cmax), indicating similar 1063 formulation performance. 1064 • Remdesivir 75 mg lyophilized formulation administered IV over 30 minutes 1065 provided similar peripheral blood mononuclear cell (PBMC) exposure of the 1066 active triphosphate metabolite GS-443902 as remdesivir 150 mg lyophilized 1067 formulation administered IV over 2 hours. 1068 • Following a single 150 mg intravenous dose of [14C]-remdesivir, mean total 1069 recovery of the dose was greater than 92%, consisting of approximately 74% 1070 and 18% recovered in urine and feces, respectively. The majority of 1071 remdesivir dose recovered in urine was metabolite GS-441524 (49%), while 1072 10% was recovered as remdesivir. 1073 1074 Specific Populations 1075 1076 Sex, Race and Age 1077 Pharmacokinetic differences based on sex, race, and age have not been 1078 evaluated. 1079 1080 Pediatric Patients 1081 The pharmacokinetics of remdesivir in pediatric patients has not been evaluated. 1082 1083 Physiologically-based pharmacokinetic models were developed to estimate 1084 remdesivir and GS-441524 exposure and predict pediatric patient exposure 1085 based on age-dependent physiologic changes (e.g., organ volume/function,

30 1086 blood flow). These simulations do not account for the impact of infection on the 1087 pharmacokinetics of remdesivir and GS-441524, which is currently unknown. 1088 1089 Renal Impairment 1090 Because the excipient SBECD is renally cleared and accumulates in patients 1091 with decreased renal function, administration of drugs formulated with SBECD 1092 (such as remdesivir) is not recommended in adult and pediatric patients (>28 1093 days old) with eGFR less than 30 mL per minute or in full-term neonates (≥7 1094 days and ≤28 days old) with serum creatinine clearance ≥1 mg/dL unless the 1095 potential benefit outweighs the potential risk. 1096 1097 15. MICROBIOLOGY/RESISTANCE INFORMATION 1098 Antiviral Activity 1099 Remdesivir exhibited cell culture antiviral activity against a clinical isolate of 1100 SARS-CoV-2 in primary human airway epithelial (HAE) cells with a 50% effective 1101 concentration (EC50) of 9.9 nM after 48 hours of treatment. The EC50 values of 1102 remdesivir against SARS-CoV-2 in Vero cells was 137 nM at 24 hours and 750 1103 nM at 48 hours post-treatment. 1104 1105 Resistance 1106 No clinical data are available on the development of SARS-CoV-2 resistance to 1107 remdesivir. The cell culture development of SARS-CoV-2 resistance to 1108 remdesivir has not been assessed to date. 1109 1110 Cell culture resistance profiling of remdesivir using the rodent CoV murine 1111 hepatitis virus identified 2 substitutions (F476L and V553L) in the viral RNA- 1112 dependent RNA polymerase at residues conserved across CoVs that conferred a 1113 5.6 fold reduced susceptibility to remdesivir. The mutant viruses showed reduced 1114 viral fitness in cell culture and introduction of the corresponding substitutions 1115 (F480L and V557L) into SARS-CoV resulted in 6-fold reduced susceptibility to 1116 remdesivir in cell culture and attenuated SARS-CoV pathogenesis in a mouse 1117 model. 1118 1119 16. NONCLINICAL TOXICOLOGY 1120 The nonclinical toxicology profile of remdesivir has been characterized through 1121 the conduct of repeat-dose studies in rats and cynomolgus monkeys with once- 1122 daily dosing up to 4 weeks in duration, studies to evaluate the genotoxic potential 1123 of the compound, a battery of reproduction and developmental studies (fertility in 1124 rats, embryofetal development in rats and rabbits, and a pre- and post- 1125 developmental study in rats), and a hemolysis/blood compatibility study. 1126 Following repeated dosing in rats and monkeys, the kidney was identified as the 1127 target organ. In both species, clinical chemistry, urinalysis, and/or urinary 1128 biomarkers were early predictors of the observed kidney changes.

31 1129 1130 Carcinogenesis 1131 1132 Given the short-term administration of remdesivir for the treatment of COVID-19, 1133 long-term animal studies to evaluate the carcinogenic potential of remdesivir are 1134 not required. 1135 1136 Mutagenesis 1137 1138 Remdesivir was not genotoxic in a battery of assays, including bacterial 1139 mutagenicity, chromosome aberration using human peripheral blood 1140 lymphocytes, and in vivo rat micronucleus assays. 1141 1142 Impairment of Fertility 1143 1144 Nonclinical toxicity studies in rats demonstrated no adverse effect on male fertility 1145 at exposures of the predominant circulating metabolite (GS-441524) 1146 approximately 2 times the exposure in humans at the RHD. 1147 1148 Reproductive toxicity, including decreases in corpora lutea, numbers of 1149 implantation sites, and viable embryos, was seen when remdesivir was 1150 administered intravenous daily at a systemically toxic dose (10 mg/kg) in female 1151 rats 14 days prior to mating and during conception; exposures of the 1152 predominant circulating metabolite (GS-441524) were 1.3 times the exposure in 1153 humans at the RHD. 1154 1155 Animal Toxicology and/or Pharmacology 1156 1157 Intravenous administration (slow bolus) of remdesivir to male rhesus monkeys at 1158 dosage levels of 5, 10, and 20 mg/kg/day for 7 days resulted, at all dose levels, 1159 in increased mean urea nitrogen and increased mean creatinine, renal tubular 1160 atrophy, and basophilia and casts. 1161 1162 Intravenous administration (slow bolus) of remdesivir to rats at dosage levels of 1163 ≥3 mg/kg/day for up to 4 weeks resulted in findings indicative of kidney injury 1164 and/or dysfunction. 1165 1166 17. ANIMAL PHARMACOLOGIC AND EFFICACY DATA 1167 It is unknown, at present, how the observed antiviral activity of remdesivir in 1168 animal models of SARS-CoV-2 infection will translate into clinical efficacy in 1169 patients with symptomatic disease. Key attributes of the remdesivir nonclinical 1170 profile supporting its development for the treatment of COVID-19 are provided 1171 below: 1172

32 1173 • Remdesivir showed cell culture antiviral activity against a clinical isolate of 1174 SARS-CoV-2 in primary HAE cells (EC50 value= 9.9 nM). The EC50 values 1175 of remdesivir against SARS-CoV-2 in Vero cells has been reported to be 1176 137 nM at 24 hours and 750 nM at 48 hours post-treatment. 1177 1178 • Remdesivir showed antiviral activity in SARS-CoV-2-infected rhesus 1179 monkeys. Administration of remdesivir at 10/5 mg/kg (10 mg/kg first dose, 1180 followed by 5 mg/kg once daily thereafter) using IV bolus injection initiated 1181 12 hours post-inoculation with SARS-CoV-2 resulted in a reduction in 1182 clinical signs of respiratory disease, lung pathology and gross lung 1183 lesions, and lung viral RNA levels compared with vehicle-treated animals. 1184 1185 18. CLINICAL TRIAL RESULTS AND SUPPORTING DATA FOR EUA 1186 Remdesivir is an unapproved antiviral drug with available data from two 1187 randomized clinical trials and a compassionate use program in patients with 1188 COVID-19, and from clinical trials in healthy volunteers and subjects with Ebola 1189 virus disease. 1190 1191 Clinical Trials in Subjects with COVID-19 1192 1193 NIAID ACTT-1 Study 1194 1195 A randomized, double-blind, placebo-control clinical trial evaluated remdesivir 1196 200 mg once daily for 1 day followed by remdesivir 100 mg once daily for 9 days 1197 (for a total of up to 10 days of intravenously administered therapy) in hospitalized 1198 adult patients with COVID-19. The trial enrolled 1063 hospitalized patients in a 1199 1:1 manner to receive remdesivir or placebo. The primary clinical endpoint was 1200 time to recovery within 28 days after randomization. In a preliminary analysis of 1201 the primary endpoint performed after 606 recoveries were attained, the median 1202 time to recovery was 11 days in the remdesivir group compared to 15 days in the 1203 placebo group (hazard ratio 1.31; 95% CI 1.12 to 1.54, p<0.001). Mortality was 1204 8.0% for the remdesivir group versus 11.6% for the placebo group (p=0.059). 1205 1206 1207 Study GS-US-540-5773 1208 A randomized, open-label multi-center clinical trial (Study GS-US-540-5773) of 1209 patients with severe COVID-19 compared 197 adult patients who received 1210 remdesivir 200 mg once daily followed by remdesivir 100 mg once daily for 9 1211 days (for a total of 10 days of intravenously administered therapy) with 200 adult 1212 patients who received remdesivir 200 mg once daily followed by remdesivir 100 1213 mg for 4 days (for a total of 5 days of intravenously administered therapy), plus 1214 standard of care. The primary clinical endpoint was clinical status assessed by a 1215 7-point ordinal scale at Day 14 after randomization. The study suggested that 1216 patients receiving a 10-day treatment course of remdesivir had similar 1217 improvement in clinical status compared with those receiving a 5-day treatment

33 1218 course (10-to-5 day odds ratio: 0.76; 95% confidence interval [CI] 0.51 to 1.13] 1219 on Day 14). 1220 1221 Clinical improvement was defined as an improvement of two or more points from 1222 baseline on a predefined 7-point scale, ranging from hospital discharge to 1223 increasing levels of oxygen support to death. Patients achieved clinical recovery 1224 if they no longer required oxygen support or were discharged from the hospital. 1225 1226 The time to clinical improvement for 50% of patients was 10 days in the 5-day 1227 treatment group and 11 days in the 10-day treatment group. At Day 14, observed 1228 rates between the 5- and 10-day treatment groups were 65% vs 54% for clinical 1229 improvement, 70% vs 59% for clinical recovery, and 8% vs 11% for mortality. 1230 1231 Compassionate Use Program in Patients with COVID-19 1232 1233 Remdesivir has been provided through a compassionate use multi-center, open- 1234 label program to over 1,200 adult patients with confirmed SARS-CoV-2 infection 1235 by polymerase chain reaction (PCR) and manifestations of severe disease. In 1236 addition, remdesivir has been provided to 76 pediatric patients <18 years of age 1237 and 96 pregnant women through the compassionate use program. 1238 Patients were treated with remdesivir 200 mg once daily followed by remdesivir 1239 100 mg for 9 days intravenously, plus standard of care, for a total of up to 10 1240 days of therapy. 1241 1242 Clinical Studies in Healthy Adults 1243 1244 Remdesivir was evaluated in four Phase 1 studies in 138 healthy adult volunteers 1245 (Studies GS-US-399-1812, GS-US-399-1954, GS-US-399-4231, and GS-US- 1246 399-5505). In these studies, transient graded elevations in ALT and AST were 1247 observed at repeated once-daily doses of remdesivir. 1248 1249 Clinical Study in Subjects with Ebola Virus Disease 1250 1251 Supportive safety data are provided from the PALM study, a Phase 2/3, open- 1252 label, randomized, parallel group study to assess the safety and efficacy of 1253 investigational treatments, including remdesivir, in patients with Ebola virus 1254 disease. 175 patients were randomized to receive remdesivir. A total of 9 SAEs 1255 judged by the site investigator as not related to underlying Ebola virus disease 1256 were reported for participants receiving remdesivir. Of these, an event of 1257 hypotension, which occurred during administration of the loading dose and led to 1258 fatal cardiac arrest, was considered related to remdesivir. The independent 1259 pharmacovigilance committee noted that the death could not be readily 1260 distinguished from underlying fulminant Ebola virus disease. 1261 1262 19. HOW SUPPLIED/STORAGE AND HANDLING

34 1263 How Supplied

1264 Lyophilized Powder

1265 Remdesivir for injection, 100 mg, is supplied as a single-dose vial containing a 1266 sterile, preservative-free white to off-white to yellow lyophilized powder that is to 1267 be reconstituted with 19 mL of Sterile Water for Injection and diluted into 0.9% 1268 saline prior to administration by intravenous infusion. Following reconstitution, 1269 each vial contains 5 mg/mL remdesivir reconcentrated solution with sufficient 1270 volume to allow withdrawal of 20 mL of 5 mg/mL solution containing 100 mg of 1271 remdesivir.

1272 Discard unused portion.

1273 The container closure is not made with natural rubber latex.

1274 Injection Solution

1275 Remdesivir injection is supplied as a single dose vial containing 5 mg/mL of 1276 remdesivir per vial for dilution into 0.9% saline.

1277 Discard unused portion.

1278 The container closure is not made with natural rubber latex.

1279 Storage and Handling

1280 Do not reuse or save unused remdesivir lyophilized powder, injection solution, or 1281 diluted solution for infusion for future use. This product contains no preservative.

1282 Lyophilized Powder

1283 Store remdesivir for injection, 100 mg, vials below 30°C (below 86°F) until 1284 required for use. Do not use after expiration date.

1285 After reconstitution, vials can be stored up to 4 hours at room temperature (20°C 1286 to 25°C [68°F to 77°F]) prior to administration or 24 hours at refrigerated 1287 temperature (2°C to 8°C [36°F to 46°F]). Dilute within the same day as 1288 administration.

1289 Injection Solution

1290 Store remdesivir injection, 5 mg/mL, vials at refrigerated temperature (2°C to 8°C 1291 [36°F to 46°F]) until required for use. Do not use after expiration date. Dilute 1292 within the same day as administration.

1293 Prior to dilution, equilibrate remdesivir injection to room temperature (20°C to 1294 25°C [68°F to 77°F]). Sealed vials can be stored up to 12 hours at room 1295 temperature prior to dilution.

35 1296 Diluted Solution for Infusion

1297 Store diluted remdesivir solution for infusion up to 4 hours at room temperature 1298 (20°C to 25°C [68°F to 77°F]) or 24 hours at refrigerated temperature (2°C to 8°C 1299 [36°F to 46°F]).

1300 1301 20. PATIENT COUNSELING INFORMATION 1302 1303 SEE Fact Sheet for Patients and Parents/Caregivers 1304 1305 21. CONTACT INFORMATION 1306 If you have questions, please contact 1307 www.askgileadmedical.com 1308 1-866-633-4474 1309 1310

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