., atrial fibrillation, sinus tachycardia, bradycardia), chest pain or discomfort, weakness, altered mental status, nausea, headache, bronchospasm, hypotension, hypertension, angioedema, throat irritation, rash including urticaria, pruritus, myalgia, vasovagal reactions (e.g., pre-syncope, syncope), dizziness and diaphoresis. consider slowing or stopping the infusion and administer appropriate medications and/or supportive care if an infusion-related reaction occurs. hypersensitivity reactions occurring more than 24 hours after the infusion have also been reported with the use of bamlanivimab and etesevimab under emergency use authorization. clinical worsening after bamlanivimab and etesevimab administration clinical worsening of covid-19 after administration of bamlanivimab and etesevimab together has been reported and may include signs or symptoms of fever, hypoxia or increased respiratory difficulty, arrhythmia (e.g., atrial fibrillation, sinus tachycardia, bradycardia), fatigue, and altered mental status. some of these events required hospitalization. it is not known if these events were related to bamlanivimab and etesevimab use or were due to progression of covid-19. limitations of benefit and potential for risk in patients with severe covid-19 treatment with bamlanivimab and etesevimab has not been studied in patients hospitalized due to covid-19. monoclonal antibodies, such as bamlanivimab and etesevimab, may be associated with worse clinical outcomes when administered to hospitalized patients with covid-19 requiring high flow oxygen or mechanical ventilation. therefore, [see limitations of authorized use ( 1.1 )] : bamlanivimab and etesevimab are not authorized for use in patients 2 years and older who are hospitalized due to covid-19 , bamlanivimab and etesevimab are not authorized for use in patients, regardless of age, who: require oxygen therapy and/or respiratory support due to covid-19, or require an increase in baseline oxygen flow rate and/or respiratory support due to covid-19 and are on chronic oxygen therapy and/or respiratory support due to underlying non-covid-19 related comorbidity.

duced oxygen saturation, chills, fatigue, arrhythmia (e.g., atrial fibrillation, sinus tachycardia, bradycardia), chest pain or discomfort, weakness, altered mental status, nausea, headache, bronchospasm, hypotension, hypertension, angioedema, throat irritation, rash including urticaria, pruritus, myalgia, vasovagal reactions (e.g., pre-syncope, syncope), dizziness and diaphoresis. consider slowing or stopping the infusion and administer appropriate medications and/or supportive care if an infusion-related reaction occurs. hypersensitivity reactions occurring more than 24 hours after the infusion have also been reported with the use of bamlanivimab and etesevimab under emergency use authorization. 5.2 clinical worsening after bamlanivimab and etesevimab administration clinical worsening of covid-19 after administration of bamlanivimab and etesevimab together has been reported and may include signs or symptoms of fever, hypoxia or increased respiratory difficulty, arrhythmia (e.g., atrial fibrillation, sinus tachycardia, bradycardia), fatigue, and altered mental status. some of these events required hospitalization. it is not known if these events were related to bamlanivimab and etesevimab use or were due to progression of covid-19. 5.3 limitations of benefit and potential for risk in patients with severe covid-19 treatment with bamlanivimab and etesevimab has not been studied in patients hospitalized due to covid-19. monoclonal antibodies, such bamlanivimab and etesevimab, may be associated with worse clinical outcomes when administered to hospitalized patients with covid-19 requiring high flow oxygen or mechanical ventilation. therefore, bamlanivimab and etesevimab are not authorized for use in patients 2 years and older who are hospitalized due to covid-19 , bamlanivimab and etesevimab are not authorized for use in patients, regardless of age, who: require oxygen therapy and/or respiratory support due to covid-19, or require an increase in baseline oxygen flow rate and/or respiratory support due to covid-19 and are on chronic oxygen therapy and/or respiratory support due to underlying non-covid-19 related comorbidity [see limitations of authorized use ( 1.1 )] .

-19)) other medical conditions or factors (for example, race or ethnicity) may also place individual patients at high risk for progression to severe covid-19 and authorization of bamlanivimab and etesevimab under the eua is not limited to the medical conditions or factors listed above. for additional information on medical conditions and factors associated with increased risk for progression to severe covid-19, see the cdc website: https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/people-with-medical-conditions.html . healthcare providers should consider the benefit-risk for an individual patient. 2.2 dosage treatment : the dosage in adults (18 years and older) and pediatric patients (<18 years and weighing at least 40 kg) is bamlanivimab 700 mg and etesevimab 1,400 mg. the dosage for pediatric patients weighing less than 40 kg will vary depending on body weight: >20 kg to <40 kg: 350 mg bamlanivimab and 700 mg etesevimab >12 kg to 20 kg: 175 mg bamlanivimab and 350 mg etesevimab 1 kg to 12 kg: 12 mg/kg bamlanivimab and 24 mg/kg etesevimab the recommended dosing regimen for pediatric patients ?12 kg is predicted based on pharmacokinetic modeling and simulation [see clinical pharmacology ( 14.3 )] . the youngest participant in the pediatric clinical trial for treatment was 10 months of age and weighed 8.6 kg [see use in specific populations ( 11.3 ) and clinical trials and supporting data for eua ( 18.1 )] . for treatment of covid-19, bamlanivimab and etesevimab should be administered together as soon as possible after positive results of direct sars-cov-2 viral testing and within 10 days of symptom onset. post-exposure prophylaxis : the dosage in adults (18 years and older) and pediatric individuals (<18 years and weighing at least 40 kg) is 700 mg bamlanivimab and 1,400 mg etesevimab administered together as a single intravenous infusion. the dosage for pediatric individuals weighing less than 40 kg will vary depending on body weight: >20 kg to <40 kg: 350 mg bamlanivimab and 700 mg etesevimab >12 kg to 20 kg: 175 mg bamlanivimab and 350 mg etesevimab 1 kg to 12 kg: 12 mg/kg bamlanivimab and 24 mg/kg etesevimab the recommended dosing regimen for pediatric patients ?12 kg is predicted based on pharmacokinetic modeling and simulation [see clinical pharmacology ( 14.3 )] . the youngest participant in the pediatric clinical trial for treatment was 10 months of age and weighed 8.6 kg [see use in specific populations ( 11.3 ) and clinical trials and supporting data for eua ( 18.1 )] . children were not enrolled in the post-exposure prophylaxis trial, blaze-2 [see clinical trials and supporting data for eua ( 18.2 )] . for post-exposure prophylaxis, bamlanivimab and etesevimab should be given together as soon as possible following exposure to sars-cov-2. under this eua, bamlanivimab and etesevimab must be administered together as a single intravenous infusion. 2.3 dosage adjustment in specific populations pregnancy or lactation no dosage adjustment is recommended in pregnant or lactating women [see use in specific populations ( 11.1 , 11.2 )] . pediatric use no dosage adjustment is recommended in pediatric patients <18 years who weigh at least 40 kg. for pediatric patients weighing less than 40 kg, dosage adjustment on the basis of body weight is required [see dosage and administration ( 2.4 )] . the recommended dosing regimen for pediatric patients ?12 kg is predicted based on pharmacokinetic modeling and simulation [see clinical pharmacology ( 14.3 )] . the youngest participant in the pediatric clinical trial for treatment was 10 months of age and weighed 8.6 kg [see use in specific populations ( 11.3 ) and clinical trials and supporting data for eua ( 18.1 )] . children were not enrolled in the post-exposure prophylaxis trial, blaze-2 [see clinical trials and supporting data for eua ( 18.2 )] . geriatric use no dosage adjustment is recommended in geriatric patients [see use in specific populations ( 11.4 )] . renal impairment no dosage adjustment is recommended in patients with renal impairment [see use in specific populations ( 11.5 )] . hepatic impairment no dosage adjustment is recommended in patients with mild hepatic impairment. bamlanivimab and etesevimab has not been studied in patients with moderate or severe hepatic impairment [see use in specific populations ( 11.6 )] . 2.4 dose preparation and administration general information bamlanivimab and etesevimab solution for infusion should be prepared by a qualified healthcare professional using aseptic technique. bamlanivimab and etesevimab are supplied in individual vials but are administered together. inspect bamlanivimab and etesevimab vials visually for particulate matter and discoloration. bamlanivimab and etesevimab are clear to opalescent and colorless to slightly yellow to slightly brown solutions. the prepared infusion solution should not be administered simultaneously with any other medication. the compatibility of bamlanivimab and etesevimab injection with iv solutions and medications other than 0.9% sodium chloride injection is not known. if the infusion must be discontinued due to an infusion reaction, discard any unused product. the use of closed system transfer devices (cstds), elastomeric pumps, and pneumatic transport with bamlanivimab and etesevimab has not been studied. clinically monitor patients during administration and observe patients for at least 1 hour after infusion is complete. iv infusion in adults (?18 years regardless of weight) and pediatric patients (<18 years and weighing at least 40 kg) materials needed 1 bamlanivimab vial (700 mg/20 ml) 2 etesevimab vials (700 mg/20 ml) 1 polyvinyl chloride (pvc) or polyethylene (pe)-line pvc, sterile prefilled infusion bag containing 0.9% sodium chloride injection (sizes 50 ml to 250 ml) 1 pvc or pe-lined pvc infusion set 1 in-line or add-on 0.2/0.22 micron polyethersulfone (pes) filter 0.9% sodium chloride for flushing tubing preparation remove 1 bamlanivimab vial and 2 etesevimab vials from refrigerated storage and allow to equilibrate to room temperature for approximately 20 minutes before preparation. do not expose to direct heat. do not shake the vials. inspect vials. withdraw 20 ml from one bamlanivimab vial and 40 ml from two etesevimab vials and inject all 60 ml into a prefilled infusion bag containing 0.9% sodium chloride (see table 1 ). discard any product remaining in the vials. gently invert the bag by hand approximately 10 times to mix. do not shake. table 1: recommended dilution and administration instructions for bamlanivimab and etesevimab for iv infusion a in adults (?18 years regardless of weight) and pediatric patients (<18 years and weighing at least 40 kg) a 700 mg of bamlanivimab and 1,400 mg of etesevimab are added to the same infusion bag and administered together as a single intravenous infusion. b the minimum infusion time for patients weighing at least 40 kg and less than 50 kg who are administered bamlanivimab and etesevimab diluted in a 250-ml prefilled 0.9% sodium chloride infusion bag must be extended to at least 70 minutes to reduce endotoxin load. drug a : add 20 ml of bamlanivimab (1 vial) and 40 ml of etesevimab (2 vials) for a total of 60 ml to a prefilled infusion bag and administer as instructed below size of prefilled 0.9% sodium chloride infusion bag maximum infusion rate minimum infusion time 50 ml 310 ml/hr 21 minutes 100 ml 310 ml/hr 31 minutes 150 ml 310 ml/hr 41 minutes 250 ml for patients weighing at least 50 kg 310 ml/hr 60 minutes 250 ml b for patients weighing ?40 kg and <50 kg 266 ml/hr 70 minutes administration these products are preservative-free and therefore, the diluted infusion solution should be administered immediately. if immediate administration is not possible, store the diluted infusion solution for up to 24 hours at refrigerated temperature (2°c to 8°c [36°f to 46°f]) and up to 7 hours at room temperature (20°c to 25°c [68°f to 77°f]) including infusion time. if refrigerated, allow the infusion solution to equilibrate to room temperature for approximately 20 minutes prior to administration. attach the infusion set to the iv bag. use of in-line or add-on 0.2/0.22 micron polyethersulfone (pes) filter is strongly recommended. prime the infusion set. administer the entire infusion solution in the bag via pump or gravity according to the size of infusion bag used (see table 1 ). due to potential overfill of prefilled saline bags, the entire infusion solution in the bag should be administered to avoid underdosage. once infusion is complete, flush the tubing with 0.9% sodium chloride to ensure delivery of the required dose. iv infusion in pediatric patients (<18 years and weighing <40 kg) materials needed iv bag syringe pump 1 bamlanivimab vial (700 mg/20 ml) 1 bamlanivimab vial (700 mg/20 ml) 1 etesevimab vial (700 mg/20 ml) 1 etesevimab vial (700 mg/20 ml) 1 sterile, empty 50-ml pvc or pe-lined pvc infusion bag 1 disposable syringe 1 pvc or pe-lined pvc infusion set 1 syringe extension set 1 in-line or add-on 0.2/0.22 micron pes filter 1 syringe pump 0.9% sodium chloride for flushing 0.9% sodium chloride for flushing under this eua, single-dose vials may be used to prepare more than one pediatric dose; in addition, pediatric doses do not need to be diluted for patients <18 years and weighing <40 kg. preparation remove bamlanivimab and etesevimab vials from refrigerated storage and allow to equilibrate to room temperature for approximately 20 minutes before preparation. do not expose to direct heat. do not shake vials. inspect vials. withdraw appropriate amounts of bamlanivimab and etesevimab from vials based on body weight and inject into the empty infusion bag or draw into a disposable syringe (see table 2 ). multiple doses of bamlanivimab and etesevimab may be prepared from each product vial (see the storage conditions specified below ). prepare all infusion bags or syringes at the same time. appropriately label any prepared doses including the patient weight and dose, and time of preparation to minimize risk of medication errors, particularly in cases where multiple doses are prepared simultaneously. discard any product remaining in the vials after all doses have been prepared. gently invert the infusion bag or syringe to mix the contents. do not shake or vigorously agitate. table 2: recommended dosing, preparation and administration instructions for undiluted bamlanivimab (bam) and etesevimab (ete) for iv infusion in pediatric patients (<18 years and weighing less than 40 kg) a amount of bam (as ml) and amount of ete (as ml) for patients weighing up to 12 kg are calculated and rounded to one decimal place. body weight bam/ete dose (mg) amount of bam (as ml) a amount of ete (as ml) a maximum infusion rate >20 kg to <40 kg 350 mg / 700 mg 10 ml 20 ml 1.88 ml/min >12 kg to 20 kg 175 mg / 350 mg 5 ml 10 ml 0.94 ml/min >11 kg to 12 kg 138 mg / 276 mg 3.9 ml 7.9 ml 0.74 ml/min >10 kg to 11 kg 126 mg / 252 mg 3.6 ml 7.2 ml 0.68 ml/min >9 kg to 10 kg 114 mg / 228 mg 3.3 ml 6.5 ml 0.61 ml/min >8 kg to 9 kg 102 mg / 204 mg 2.9 ml 5.8 ml 0.54 ml/min >7 kg to 8 kg 90 mg / 180 mg 2.6 ml 5.1 ml 0.48 ml/min >6 kg to 7 kg 78 mg / 156 mg 2.2 ml 4.5 ml 0.42 ml/min >5 kg to 6 kg 66 mg / 132 mg 1.9 ml 3.8 ml 0.36 ml/min >4 kg to 5 kg 54 mg / 108 mg 1.5 ml 3.1 ml 0.29 ml/min >3 kg to 4 kg 42 mg / 84 mg 1.2 ml 2.4 ml 0.23 ml/min >2 kg to 3 kg 30 mg / 60 mg 0.9 ml 1.7 ml 0.16 ml/min >1.5 kg to 2 kg 21 mg / 42 mg 0.6 ml 1.2 ml 0.11 ml/min 1 kg to 1.5 kg 15 mg / 30 mg 0.4 ml 0.9 ml 0.08 ml/min administration these products are preservative-free and therefore, the infusion solution should be administered immediately. if immediate administration is not possible, store the infusion solution for up to 24 hours at refrigerated temperature (2°c to 8°c [36°f to 46°f]) and up to 7 hours at room temperature (20°c to 25°c [68°f to 77°f]) including infusion time. if refrigerated, allow the infusion solution to equilibrate to room temperature for approximately 20 minutes prior to administration. iv bag: attach the infusion set to the iv bag. use of in-line or add-on 0.2/0.22 micron polyethersulfone (pes) filter is strongly recommended. prime the infusion set. administer the entire infusion solution in the bag via pump or gravity over at least 16 minutes (see table 2 ). once infusion is complete, flush the tubing with 0.9% sodium chloride to ensure delivery of the required dose. syringe pump: administer the entire contents of the syringe via syringe pump over at least 16 minutes (see table 2 ). after the entire contents of the syringe have been administered, flush the extension set with 0.9% sodium chloride to ensure delivery of the required dose.

disability, or congenital anomaly. if a serious and unexpected adverse event occurs and appears to be associated with the use of bamlanivimab and etesevimab under this eua, the prescribing healthcare provider and/or the provider's designee must 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 complete and submit a postage-paid fda form 3500 ( https://www.fda.gov/media/76299/download ) and return by: mail to medwatch, 5600 fishers lane, rockville, md 20852-9787, or fax (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 that must be included: patient demographics (e.g., patient initials, date of birth) pertinent medical history pertinent details regarding adverse events and course of illness concomitant medications timing of adverse event(s) in relationship to administration of bamlanivimab and etesevimab 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 “bamlanivimab and etesevimab use for covid-19 under emergency use authorization (eua)” as the first line provide a detailed report of medication error and/or adverse event. it is important to provide detailed information regarding the patient and adverse event/medication error for ongoing safety evaluation of this unapproved drug. please see information to include listed above. in section g, box 1, name and address: provide the name and contact information of the prescribing healthcare provider or institutional designee who is responsible for the report. provide the address of the treating institution (not the healthcare provider's office address).

nefit or risk to the developing fetus. the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. clinical considerations disease-associated maternal and/or embryo-fetal risk covid-19 in pregnancy is associated with adverse maternal and fetal outcomes, including preeclampsia, eclampsia, preterm birth, premature rupture of membranes, venous thromboembolic disease, and fetal death. 11.2 lactation risk summary there are no available data on the presence of bamlanivimab or etesevimab in human or animal milk, the effects on the breastfed infant, or the effects on milk production. maternal igg is known to be present in human milk. the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for bamlanivimab and etesevimab and any potential adverse effects on the breastfed child from bamlanivimab and etesevimab or from the underlying maternal condition. breastfeeding individuals with covid-19 should follow practices according to clinical guidelines to avoid exposing the infant to covid-19. 11.3 pediatric use bamlanivimab and etesevimab administered together are authorized for the treatment of mild to moderate covid-19 and post-exposure prophylaxis for prevention of covid-19 in pediatric patients, including neonates [see authorized use ( 1 )] . given the similar course of covid-19, the authorization of bamlanivimab and etesevimab for treatment and post-exposure prophylaxis in younger pediatric patients, including neonates, is supported by safety and efficacy data in adolescents and adults, together with additional pharmacokinetic and safety data from the clinical trial in pediatric patients studying bamlanivimab and etesevimab for the treatment of mild to moderate covid-19. use of bamlanivimab and etesevimab in pediatric patients is based on analyses of data from blaze-1 in subjects aged 10 months to 18 years of age [see clinical pharmacology ( 14.3 ) and clinical trials and supporting data for eua ( 18.1 )] . no dosage adjustment is recommended in pediatric patients 12-18 years of age who weigh at least 40 kg. pediatric patients weighing less than 40 kg should be dosed on the basis of body weight [see dosage and administration ( 2.2 , 2.4 )] . the recommended dosing regimen for pediatric patients ?12 kg is predicted based on pharmacokinetic modeling and simulation [see clinical pharmacology ( 14.3 )] . the youngest participant in the pediatric clinical trial for treatment was 10 months of age and weighed 8.6 kg [see clinical trials and supporting data for eua ( 18.1 )] . safety in pediatric patients was similar to what was observed in adults [see clinical trial experience ( 6.1 )] . children were not enrolled in the post-exposure prophylaxis trial, blaze-2 [see clinical trials and supporting data for eua ( 18.2 )] . 11.4 geriatric use of the 1141 patients receiving bamlanivimab and etesevimab in blaze-1, 30% were 65 years of age and older and 10% were 75 years of age and older. based on population pk analyses, there is no difference in pk of bamlanivimab or etesevimab in geriatric patients compared to younger patients [see clinical trial results and supporting data for eua ( 18.1 )] . 11.5 renal impairment bamlanivimab and etesevimab are not eliminated intact in the urine, thus renal impairment is not expected to affect the exposure of bamlanivimab or etesevimab. 11.6 hepatic impairment based on population pk analysis, there is no difference in pk of bamlanivimab or etesevimab in patients with mild hepatic impairment compared to patients with normal hepatic function. bamlanivimab and etesevimab have not been studied in patients with moderate or severe hepatic impairment. 11.7 other specific populations based on population pk analysis, the pk of bamlanivimab and etesevimab was not affected by sex, race, or disease severity. body weight had no clinically relevant effect on the pk of bamlanivimab and etesevimab in adults with covid-19 over the body weight range of 41 kg to 173 kg.

fetus. the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. clinical considerations disease-associated maternal and/or embryo-fetal risk covid-19 in pregnancy is associated with adverse maternal and fetal outcomes, including preeclampsia, eclampsia, preterm birth, premature rupture of membranes, venous thromboembolic disease, and fetal death.

8 years of age who weigh at least 40 kg. pediatric patients weighing less than 40 kg should be dosed on the basis of body weight [see dosage and administration ( 2.2 , 2.4 )] . the recommended dosing regimen for pediatric patients ?12 kg is predicted based on pharmacokinetic modeling and simulation [see clinical pharmacology ( 14.3 )] . the youngest participant in the pediatric clinical trial for treatment was 10 months of age and weighed 8.6 kg [see clinical trials and supporting data for eua ( 18.1 )] . safety in pediatric patients was similar to what was observed in adults [see clinical trial experience ( 6.1 )] . children were not enrolled in the post-exposure prophylaxis trial, blaze-2 [see clinical trials and supporting data for eua ( 18.2 )] .

exposure-response relationship for efficacy was identified for bamlanivimab and etesevimab administered together within the dose range of 700 mg bamlanivimab and 1,400 mg etesevimab to 2,800 mg bamlanivimab and 2,800 mg etesevimab (4 and 2 times the authorized dose, respectively), based on clinical data and pharmacokinetic/pharmacodynamic modeling. for post-exposure prophylaxis of covid-19, a dose of 700 mg bamlanivimab and 1,400 mg etesevimab was supported based on clinical data and pharmacokinetic/pharmacodynamic modeling. 14.3 pharmacokinetics a summary of pk parameters of bamlanivimab and etesevimab following administration of a single dose of 700 mg bamlanivimab and 1,400 mg etesevimab is provided in table 3 . there is no change in pk of bamlanivimab or etesevimab administered alone or together suggesting there is no interaction between the two antibodies. there were no differences in pk of etesevimab between mild/moderate ambulatory participants and healthy participants. table 3: pharmacokinetic parameters of bamlanivimab (bam) and etesevimab (ete) administered iv in adults abbreviations: cv = coefficient of variation; c max = maximum concentration; auc inf = area under the concentration versus time curve from zero to infinity; vss = steady-state volume of distribution. a n = number of subjects simulated using the pk model. b the number of subjects for vss, half-life, and clearance are based on a population pk model that included bamlanivimab doses up to 7,000 mg and etesevimab doses up to 2,800 mg. n bam (700 mg) ete (1400 mg) systemic exposure geometric mean (%cv) c max , mcg/ml 270 187 (41.7) 422 (41.2) geometric mean (%cv) c day 29 , mcg/ml 311 bam; 320 ete 25.7 (42.9) 116 (38.1) median (5 th ,95 th percentile) c week 8 , mcg/ml 1000 a 10.1 (3.59, 22.9) 58.3 (26.8, 117) geometric mean (%cv) auc inf , mcg day/ml 499 2500 (28.0) 10600 (29.9) distribution geometric mean (%cv) vss (l) 1899 bam; 1498 ete b 6.59 (24.9) 5.78 (24.7) elimination geometric mean (%cv) elimination half-life (day) 1899 bam; 1498 ete b 20.9 (17.3) 32.6 (21.7) geometric mean (%cv) clearance (l/day) 1899 bam; 1498 ete b 0.274 (31.5) 0.134 (32.5) bamlanivimab and etesevimab are expected to be degraded into small peptides and component amino acids via catabolic pathways in the same manner as endogenous igg antibodies. special populations: the pk profiles of bamlanivimab and etesevimab were not affected by age, sex, race, or disease severity based on a population pk analysis. body weight had no clinically relevant effect on the pk of bamlanivimab or etesevimab in adults with covid-19 over the body weight range of 41 kg to 173 kg [see use in specific populations ( 11.4 , 11.7 )] . pediatric population the pk of bamlanivimab and etesevimab has been evaluated in 88 pediatric patients <18 years who received weight-based dosing [see dosage and administration ( 2.2 )] . the data show that weight-based dosing in pediatric patients provides comparable plasma exposures to those observed in adults who received bamlanivimab 700 mg and etesevimab 1,400 mg. no dosage adjustment is recommended in pediatric patients <18 years who weigh at least 40 kg. pediatric patients weighing less than 40 kg should be dosed on the basis of body weight [see dosage and administration ( 2.2 , 2.4 )] . the recommended dosing regimen for pediatric patients ?12 kg is predicted to result in similar exposures when compared to exposures achieved in adults receiving bamlanivimab 700 mg and etesevimab 1,400 mg based on pharmacokinetic modeling and simulation. the youngest participant in the pediatric treatment trial was 10 months of age and weighed 8.6 kg [see clinical trials and supporting data for eua ( 18.1 )] . table 4: pharmacokinetic parameters of bamlanivimab (bam) and etesevimab (ete) administered iv in pediatric patients abbreviations: cv = coefficient of variation; c max = maximum concentration; auc inf = area under the concentration versus time curve from zero to infinity. body weight ?40 kg >20 to <40 kg >12 to ?20 kg ?12 kg bam / ete dose 700 mg / 1400 mg 350 mg / 700 mg 175 mg / 350 mg 15 mg/kg / 30 mg/kg bam: geometric mean (%cv) [n] c max , mcg/ml 235 (51.0) [52] 239 (39.1) [16] 243 (66.0) [7] 371 (9.8) [2] c day 29 , mcg/ml 26.8 (50.2) [34] 26.1 (32.5) [8] 23.0 (53.0) [3] [0] auc inf , mcg day/ml 2760 (30.7) [66] 2780 (25.7) [20] 2430 (28.4) [9] 3000 (19.1) [3] ete: geometric mean (%cv) [n] c max , mcg/ml 508 (50.6) [50] 444 (26.6) [14] 444 (64.9) [7] 831 (16.8) [2] c day 29 , mcg/ml 133 (46.8) [34] 138 (29.5) [8] 125 (51.5) [3] [0] auc inf , mcg day/ml 12900 (32.4) [66] 12400 (23.2) [20] 11300 (29.6) [9] 13500 (13.0) [3] patients with renal impairment bamlanivimab and etesevimab are not eliminated intact in the urine. renal impairment is not expected to impact the pk of bamlanivimab and etesevimab, since mabs with molecular weight >69 kda are known not to undergo renal elimination. similarly, dialysis is not expected to impact the pk of bamlanivimab and etesevimab [see use in specific populations ( 11.5 )] . patients with hepatic impairment based on population pk analysis, there is no significant difference in pk of bamlanivimab or etesevimab in patients with mild hepatic impairment compared to patients with normal hepatic function. bamlanivimab and etesevimab have not been studied in patients with moderate or severe hepatic impairment [see use in specific populations ( 11.6 )] . drug interactions: bamlanivimab and etesevimab are not renally excreted or metabolized by cytochrome p450 enzymes; therefore, interactions with concomitant medications that are renally excreted or that are substrates, inducers, or inhibitors of cytochrome p450 enzymes are unlikely.

n bam (700 mg) ete (1400 mg) systemic exposure geometric mean (%cv) c max , mcg/ml 270 187 (41.7) 422 (41.2) geometric mean (%cv) c day 29 , mcg/ml 311 bam; 320 ete 25.7 (42.9) 116 (38.1) median (5 th ,95 th percentile) c week 8 , mcg/ml 1000 a 10.1 (3.59, 22.9) 58.3 (26.8, 117) geometric mean (%cv) auc inf , mcg day/ml 499 2500 (28.0) 10600 (29.9) distribution geometric mean (%cv) vss (l) 1899 bam; 1498 ete b 6.59 (24.9) 5.78 (24.7) elimination geometric mean (%cv) elimination half-life (day) 1899 bam; 1498 ete b 20.9 (17.3) 32.6 (21.7) geometric mean (%cv) clearance (l/day) 1899 bam; 1498 ete b 0.274 (31.5) 0.134 (32.5) bamlanivimab and etesevimab are expected to be degraded into small peptides and component amino acids via catabolic pathways in the same manner as endogenous igg antibodies. special populations: the pk profiles of bamlanivimab and etesevimab were not affected by age, sex, race, or disease severity based on a population pk analysis. body weight had no clinically relevant effect on the pk of bamlanivimab or etesevimab in adults with covid-19 over the body weight range of 41 kg to 173 kg [see use in specific populations ( 11.4 , 11.7 )] . pediatric population the pk of bamlanivimab and etesevimab has been evaluated in 88 pediatric patients <18 years who received weight-based dosing [see dosage and administration ( 2.2 )] . the data show that weight-based dosing in pediatric patients provides comparable plasma exposures to those observed in adults who received bamlanivimab 700 mg and etesevimab 1,400 mg. no dosage adjustment is recommended in pediatric patients <18 years who weigh at least 40 kg. pediatric patients weighing less than 40 kg should be dosed on the basis of body weight [see dosage and administration ( 2.2 , 2.4 )] . the recommended dosing regimen for pediatric patients ?12 kg is predicted to result in similar exposures when compared to exposures achieved in adults receiving bamlanivimab 700 mg and etesevimab 1,400 mg based on pharmacokinetic modeling and simulation. the youngest participant in the pediatric treatment trial was 10 months of age and weighed 8.6 kg [see clinical trials and supporting data for eua ( 18.1 )] . table 4: pharmacokinetic parameters of bamlanivimab (bam) and etesevimab (ete) administered iv in pediatric patients abbreviations: cv = coefficient of variation; c max = maximum concentration; auc inf = area under the concentration versus time curve from zero to infinity. body weight ?40 kg >20 to <40 kg >12 to ?20 kg ?12 kg bam / ete dose 700 mg / 1400 mg 350 mg / 700 mg 175 mg / 350 mg 15 mg/kg / 30 mg/kg bam: geometric mean (%cv) [n] c max , mcg/ml 235 (51.0) [52] 239 (39.1) [16] 243 (66.0) [7] 371 (9.8) [2] c day 29 , mcg/ml 26.8 (50.2) [34] 26.1 (32.5) [8] 23.0 (53.0) [3] [0] auc inf , mcg day/ml 2760 (30.7) [66] 2780 (25.7) [20] 2430 (28.4) [9] 3000 (19.1) [3] ete: geometric mean (%cv) [n] c max , mcg/ml 508 (50.6) [50] 444 (26.6) [14] 444 (64.9) [7] 831 (16.8) [2] c day 29 , mcg/ml 133 (46.8) [34] 138 (29.5) [8] 125 (51.5) [3] [0] auc inf , mcg day/ml 12900 (32.4) [66] 12400 (23.2) [20] 11300 (29.6) [9] 13500 (13.0) [3] patients with renal impairment bamlanivimab and etesevimab are not eliminated intact in the urine. renal impairment is not expected to impact the pk of bamlanivimab and etesevimab, since mabs with molecular weight >69 kda are known not to undergo renal elimination. similarly, dialysis is not expected to impact the pk of bamlanivimab and etesevimab [see use in specific populations ( 11.5 )] . patients with hepatic impairment based on population pk analysis, there is no significant difference in pk of bamlanivimab or etesevimab in patients with mild hepatic impairment compared to patients with normal hepatic function. bamlanivimab and etesevimab have not been studied in patients with moderate or severe hepatic impairment [see use in specific populations ( 11.6 )] . drug interactions: bamlanivimab and etesevimab are not renally excreted or metabolized by cytochrome p450 enzymes; therefore, interactions with concomitant medications that are renally excreted or that are substrates, inducers, or inhibitors of cytochrome p450 enzymes are unlikely.

on date) of both bamlanivimab and etesevimab following a thorough review of data submitted by eli lilly and company. the extension applies to all unopened vials of bamlanivimab and etesevimab that have been held in accordance with storage conditions. confirm the shelf-life of unopened vials of bamlanivimab and etesevimab by batch number at the fda eua website under the drug and biological therapeutic products bamlanivimab and etesevimab . this site includes a complete listing of extended expiration dates by batch number. if the batch number on the vial/carton is not included in this listing, the product is labeled with the correct expiration date. do not freeze, shake, or expose to direct light. the prepared infusion solution is intended to be used immediately. if immediate administration is not possible, store infusion solution in the refrigerator at 2°c to 8°c (36°f to 46°f) for up to 24 hours and at room temperature (20°c to 25°c [68°f to 77°f]) and for up to 7 hours, including infusion time. if refrigerated, allow the infusion solution to equilibrate to room temperature prior to administration.

ou or your child receive bamlanivimab and etesevimab or you may stop them at any time. what is covid-19? covid-19 is caused by a virus called a coronavirus, sars-cov-2. 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 your or your 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, and other conditions including obesity, seem to be at higher risk of being hospitalized for covid-19. older age, with or without other conditions, also places people at higher risk of being hospitalized for covid-19. what are the symptoms of covid-19? the symptoms of covid-19 include 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 other medical conditions to become worse. what are bamlanivimab and etesevimab? bamlanivimab and etesevimab are investigational medicines used together in adults and children who are at high risk for developing severe covid-19, including hospitalization or death for: treatment of mild to moderate symptoms of covid-19, or post-exposure prophylaxis for prevention of covid-19 in persons who are: not fully vaccinated against covid-19 (individuals are considered to be fully vaccinated 2 weeks after their second dose in a 2-dose series [such as the pfizer or moderna vaccines], or 2 weeks after a single-dose dose vaccine [such as johnson & johnson's janssen vaccine]), or are not expected to build up enough of an immune response to the complete covid-19 vaccination (for example, someone with immunocompromising conditions, including someone who is taking immunosuppressive medications), and have been exposed to someone who is infected with sars-cov-2. close contact with someone who is infected with sars-cov-2 is defined as being within 6 feet for a total of 15 minutes or more, providing care at home to someone who is sick, having direct physical contact with the person (hugging or kissing, for example), sharing eating or drinking utensils, or being exposed to respiratory droplets from an infected person (sneezing or coughing, for example). for additional details, go to https://www.cdc.gov/coronavirus/2019-ncov/if-you-are-sick/quarantine.html , or someone who is at high risk of being exposed to someone who is infected with sars-cov-2 because of occurrence of sars-cov-2 infection in other individuals in the same institutional setting (for example, nursing homes, prisons). bamlanivimab and etesevimab are investigational because they are still being studied. there is limited information known about the safety or effectiveness of using bamlanivimab and etesevimab to treatment or prevention of covid-19. bamlanivimab and etesevimab are not authorized for pre-exposure prophylaxis for prevention of covid-19. the fda has authorized the emergency use of bamlanivimab and etesevimab together for the treatment of covid-19 and the post-exposure prophylaxis for prevention of covid-19 under an emergency use authorization (eua). for more information on eua, see the section “ what is an emergency use authorization (eua)? ” at the end of this fact sheet. what should i tell the healthcare provider before i or my child receive bamlanivimab and etesevimab? tell the healthcare provider about all of your or your child's medical conditions, including: having any allergies having received a covid-19 vaccine having any serious illnesses are pregnant or plan to become pregnant are breastfeeding or plan to breastfeed are taking any medications (prescription, over-the-counter, vitamins, and herbal products) how are bamlanivimab and etesevimab given? bamlanivimab and etesevimab are given at the same time through a vein (intravenous or iv). one dose of bamlanivimab and etesevimab will be given by iv infusion. the infusion will take 16 – 60 minutes or longer. your or your child's healthcare provider will determine the duration of the infusion. what are the important possible side effects of bamlanivimab and etesevimab? possible side effects of bamlanivimab and etesevimab are: allergic reactions. allergic reactions can happen during and after infusion with bamlanivimab and etesevimab. tell your or your child's healthcare provider right away if any of the following signs and symptoms of allergic reactions occur: fever, chills, nausea, headache, shortness of breath, low or high blood pressure, rapid or slow heart rate, chest discomfort or pain, weakness, confusion, feeling tired, wheezing, swelling of the lips, face, or throat, rash including hives, itching, muscle aches, feeling faint, dizziness, and sweating. these reactions may be severe or life threatening. worsening of covid-19 symptoms after bamlanivimab and etesevimab therapy for active infection: you or your child may experience new or worsening symptoms after infusion for mild to moderate covid-19, including fever, difficulty breathing, rapid or slow heart rate, tiredness, weakness or confusion. if these occur, contact your or your child's healthcare provider or seek immediate medical attention as some of these events have required hospitalization. it is unknown if these events are related to treatment or are due to the progression of covid-19. 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 infusion site. these are not all the possible side effects of bamlanivimab and etesevimab. not a lot of people have been given bamlanivimab and etesevimab. serious and unexpected side effects may happen. bamlanivimab and etesevimab are still being studied so it is possible that all of the risks are not known at this time. it is possible that bamlanivimab and etesevimab could interfere with your or your child's body's own ability to fight off a future infection of sars-cov-2. similarly, bamlanivimab and etesevimab may reduce the body's immune response to a vaccine for sars-cov-2. specific studies have not been conducted to address these possible risks. talk to your or your child's healthcare provider if you have any questions. what other treatment choices are there? like bamlanivimab and etesevimab, fda may allow for the emergency use of other medicines to treat people with covid-19. go to https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization for information on the emergency use of other medicines that are not approved by fda to treat people with covid-19. your or your child's healthcare provider may talk with you about clinical trials you or your child may be eligible for. it is your choice whether you or your child should be treated or not to be treated with bamlanivimab and etesevimab. should you decide that you or your child should not receive bamlanivimab and etesevimab or stop it at any time, it will not change your or your child's standard medical care. what other prevention choices are there? vaccines to prevent covid-19 are approved or available under emergency use authorization. use of bamlanivimab and etesevimab does not replace vaccination against covid-19. like bamlanivimab and etesevimab, fda may allow for the emergency use of other medicines for post-exposure prophylaxis for prevention of covid-19. go to https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization for information on the emergency use of other medicines that are not approved by fda for post-exposure prophylaxis for prevention of covid-19. the healthcare provider may talk with you about clinical trials you or your child may be eligible for. bamlanivimab and etesevimab are not authorized for pre-exposure prophylaxis for prevention of covid-19. what if i am pregnant or breastfeeding? there is limited experience treating pregnant women or breastfeeding mothers with bamlanivimab and etesevimab. for a mother and unborn baby, the benefit of receiving bamlanivimab and etesevimab may be greater than the risk from the treatment. if pregnant or breastfeeding, discuss your options and specific situation with your healthcare provider. how do i report side effects with bamlanivimab and etesevimab? tell the healthcare provider right away if you or your child have any side effect that bothers you or your child, or does not go away. report side effects to fda medwatch at www.fda.gov/medwatch , call 1-800-fda-1088, or contact eli lilly and company at 1-855-lillyc19 (1-855-545-5921). how can i learn more? ask your or your child's healthcare provider visit www.lillyantibody.com 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 bamlanivimab and etesevimab available under an emergency access mechanism called an eua. the eua is supported by a secretary of health and human service (hhs) declaration that circumstances exist to justify the emergency use of drugs and biological products during the covid-19 pandemic. bamlanivimab and etesevimab have not undergone the same type of review as an fda-approved product. in issuing an eua under the covid-19 public health emergency, the fda must determine, among other things, that based on the totality of scientific evidence available, it is reasonable to believe that the product may be effective for diagnosing, treating, or preventing covid-19, or a serious or life-threatening disease or condition caused by covid-19; that the known and potential benefits of the product, when used to diagnose, treat, or prevent such disease or condition, outweigh the known and potential risks of such product; and that there are no adequate, approved and available alternatives. all of these criteria must be met to allow for the medicine to be used in the treatment of covid-19 or prevention of covid-19 during the covid-19 pandemic. the eua for bamlanivimab and etesevimab together is in effect for the duration of the covid-19 declaration justifying emergency use of these products, unless terminated or revoked (after which the products may no longer be used). literature revised december 3, 2021 eli lilly and company, indianapolis, in 46285, usa copyright © 2021, eli lilly and company. all rights reserved. ete-0005-eua pat-20211203