authorization#coviddrugs. regen-cov (casirivimab and imdevimab) is not authorized for use in patients: - who are hospitalized due to covid-19, or - who require oxygen therapy due to covid-19, or - who require an increase in baseline oxygen flow rate due to covid-19 in those on chronic oxygen therapy due to underlying non-covid-19 related comorbidity. monoclonal antibodies, such as regen-cov, may be associated with worse clinical outcomes when administered to hospitalized patients with covid-19 requiring high flow oxygen or mechanical ventilation [see warnings and precautions (5.2) ] . 1.2 post-exposure prophylaxis regen-cov (casirivimab and imdevimab) co-formulated product and regen-cov (casirivimab and imdevimab) supplied as individual vials to be administered together, is authorized for use under an eua for the post-exposure prophylaxis of covid-19 in adult and pediatric individuals (12 years of age and older weighing at least 40 kg) who are at high risk for progression to severe covid-19, including hospitalization or death, and are: not fully vaccinated individuals are considered to be fully vaccinated 2 weeks after their second vaccine dose in a 2-dose series (such as the pfizer or moderna vaccines), or 2 weeks after a single-dose vaccine (such as johnson & johnson's janssen vaccine). see this website for more details: https://www.cdc.gov/coronavirus/2019-ncov/vaccines/fully-vaccinated.html#vaccinated or who are not expected to mount an adequate immune response to complete sars-cov-2 vaccination (for example, individuals with immunocompromising conditions including those taking immunosuppressive medications see this website for more details: https://www.cdc.gov/coronavirus/2019-ncov/science/science-briefs/fully-vaccinated-people.html ) and - have been exposed to an individual infected with sars-cov-2 consistent with close contact criteria per centers for disease control and prevention (cdc) close contact with an infected individual 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). see this website for additional details: https://www.cdc.gov/coronavirus/2019-ncov/if-you-are-sick/quarantine.html or - who are at high risk of exposure to an individual 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). limitations of authorized use regen-cov is not authorized for post-exposure prophylaxis of covid-19 in geographic regions where exposure is likely to have been to a non-susceptible sars-cov-2 variant, based on available information including variant susceptibility to this drug and regional variant frequency. - fda's determination and any updates will be available at: https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization#coviddrugs. post-exposure prophylaxis with regen-cov (casirivimab and imdevimab) is not a substitute for vaccination against covid-19. regen-cov (casirivimab and imdevimab) is not authorized for pre-exposure prophylaxis for prevention of covid-19.

radycardia), 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 regen-cov under emergency use authorization. clinical worsening after regen-cov administration clinical worsening of covid-19 after administration of regen-cov has been reported and may include signs or symptoms of fever, hypoxia or increased respiratory difficulty, arrhythmia (e.g., atrial fibrillation, tachycardia, bradycardia), fatigue, and altered mental status. some of these events required hospitalization. it is not known if these events were related to regen-cov use or were due to progression of covid-19. limitations of benefit and potential for risk in patients with severe covid-19 monoclonal antibodies, such as regen-cov, may be associated with worse clinical outcomes when administered to hospitalized patients with covid-19 requiring high flow oxygen or mechanical ventilation. therefore, regen-cov is not authorized for use in patients [see limitations of authorized use (1.1) ] : who are hospitalized due to covid-19, or who require oxygen therapy due to covid-19, or who require an increase in baseline oxygen flow rate due to covid-19 in those on chronic oxygen therapy due to underlying non-covid-19 related comorbidity.

on, tachycardia, bradycardia), chest pain or discomfort, weakness, altered mental status, headache, bronchospasm, hypotension, hypertension, angioedema, throat irritation, rash including urticaria, pruritus, myalgia, vasovagal reactions (e.g., pre-syncope, syncope), dizziness, fatigue, and diaphoresis [see overall safety summary (6.1) ] . if an infusion-related reaction occurs, consider slowing or stopping the infusion and administer appropriate medications and/or supportive care. hypersensitivity reactions occurring more than 24 hours after the infusion have also been reported with the use of regen-cov under emergency use authorization. 5.2 clinical worsening after regen-cov administration clinical worsening of covid-19 after administration of regen-cov has been reported and may include signs or symptoms of fever, hypoxia or increased respiratory difficulty, arrhythmia (e.g., atrial fibrillation, tachycardia, bradycardia), fatigue, and altered mental status. some of these events required hospitalization. it is not known if these events were related to regen-cov use or were due to progression of covid-19. 5.3 limitations of benefit and potential for risk in patients with severe covid-19 monoclonal antibodies, such as regen-cov, may be associated with worse clinical outcomes when administered to hospitalized patients with covid-19 requiring high flow oxygen or mechanical ventilation. therefore, regen-cov is not authorized for use in patients [see limitations of authorized use (1.1) ] : who are hospitalized due to covid-19, or who require oxygen therapy due to covid-19, or who require an increase in baseline oxygen flow rate due to covid-19 in those on chronic oxygen therapy due to underlying non-covid-19 related comorbidity.

ov (casirivimab and imdevimab) supplied in individual vials to be administered together, in adult and pediatric individuals (12 years of age and older weighing at least 40 kg) for the post-exposure prophylaxis of covid-19 in individuals who are at high risk for progression to severe covid-19, including hospitalization or death, and are: not fully vaccinated or who are not expected to mount an adequate immune response to complete sars-cov-2 vaccination (for example, individuals with immunocompromising conditions including those taking immunosuppressive medications ) and - have been exposed to an individual infected with sars-cov-2 consistent with close contact criteria per centers for disease control and prevention (cdc) or - who are at high risk of exposure to an individual 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) [see limitations of authorized use (1.2) ] . the following medical conditions or other factors may place adults and pediatric patients (age 12-17 years and weighing at least 40 kg) at higher risk for progression to severe covid-19: older age (for example, age ≥65 years of age) obesity or being overweight (for example, bmi >25 kg/m 2 , or if age 12-17, have bmi ≥85th percentile for their age and gender based on cdc growth charts, https://www.cdc.gov/growthcharts/clinical_charts.htm) pregnancy chronic kidney disease diabetes immunosuppressive disease or immunosuppressive treatment cardiovascular disease (including congenital heart disease) or hypertension chronic lung diseases (for example, chronic obstructive pulmonary disease, asthma [moderate-to-severe], interstitial lung disease, cystic fibrosis and pulmonary hypertension) sickle cell disease neurodevelopmental disorders (for example, cerebral palsy) or other conditions that confer medical complexity (for example, genetic or metabolic syndromes and severe congenital anomalies) having a medical-related technological dependence (for example, tracheostomy, gastrostomy, or positive pressure ventilation (not related to covid-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 regen-cov 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 adult and pediatric patients (12 years of age and older weighing at least 40 kg) is 600 mg of casirivimab and 600 mg of imdevimab administered together as a single intravenous infusion or by subcutaneous injection. casirivimab and imdevimab should be given together as soon as possible after a positive viral test for sars-cov-2 and within 10 days of symptom onset. post-exposure prophylaxis: the dosage in adult and pediatric individuals (12 years of age and older weighing at least 40 kg) is 600 mg of casirivimab and 600 mg of imdevimab administered by subcutaneous injection or together as a single intravenous infusion. casirivimab and imdevimab should be given together as soon as possible following exposure to sars-cov-2. for individuals whom repeat dosing is determined to be appropriate for ongoing exposure to sars-cov-2 for longer than 4 weeks and who are not expected to mount an adequate immune response to complete sars-cov-2 vaccination, the initial dose is 600 mg of casirivimab and 600 mg of imdevimab by subcutaneous injection or intravenous infusion followed by subsequent repeat dosing of 300 mg of casirivimab and 300 mg of imdevimab by subcutaneous injection or intravenous infusion once every 4 weeks for the duration of ongoing exposure. for intravenous infusion: casirivimab and imdevimab solution co-formulated in a vial and in individual vials, including co-packaged carton and dose pack, must be diluted prior to intravenous administration. administer casirivimab and imdevimab together as a single intravenous infusion via pump or gravity (see table 1 , table 2 , table 3 and table 4 ). clinically monitor patients during infusion and observe patients for at least 1 hour after infusion is complete. for subcutaneous injection: administer casirivimab and imdevimab using the co-formulated vial or using the individual vials by subcutaneous injection (see table 5 and table 6 ). clinically monitor patients after injections and observe patients for at least 1hour. 2.3 dose 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 who weigh at least 40 kg and are older than 12 years of age. regen-cov (casirivimab and imdevimab) is not recommended for pediatric patients weighing less than 40 kg or those less than 12 years of age [see use in specific populations (11.3) ] . renal impairment no dosage adjustment is recommended in patients with renal impairment [see use in specific populations (11.5) ]. 2.4 dose preparation and administration there are two different formulations of regen-cov: casirivimab and imdevimab co-formulated solution containing two antibodies in a 1:1 ratio in a vial. casirivimab and imdevimab available as individual antibody solutions in separate vials supplied as follows: individual vials in individual cartons, or together in a single carton (also referred to as a co-packaged carton), or in a dose pack. the dose pack contains individual vials of casirivimab and imdevimab, configurations that may vary in vial size, strength and appearance and are available in dose pack configurations that include 2, 5, and 8 cartons [see full eua prescribing information, how supplied/storage and handling (19) ]. for treatment, intravenous infusion is strongly recommended. subcutaneous injection is an alternative route of administration when intravenous infusion is not feasible and would lead to delay in treatment. for post-exposure prophylaxis, either subcutaneous injection or intravenous infusion can be used. there are differences in the way the two formulations are prepared. carefully follow the preparation procedures below. casirivimab and imdevimab co-formulated solution in a vial and casirivimab or imdevimab as individual antibody solutions in separate 11.1 ml vials may be used to prepare more than one dose simultaneously as appropriate, either in intravenous bags or in syringes for subcutaneous injection. discard any product remaining in the vial. store unopened casirivimab and imdevimab vials in a refrigerator at 2°c to 8°c (36°f to 46°f) in the original carton to protect from light. unopened vials may be stored in the original carton at room temperature [up to 25°c (77°f)] and must be used within 30 days. if not used in the 30 days, discard vials. under the eua, a single-dose vial may be used to prepare more than one dose. preparation for intravenous infusion for treatment, the preferred route of administration for casirivimab and imdevimab is by intravenous infusion after dilution. casirivimab and imdevimab solution for intravenous infusion should be prepared by a qualified healthcare professional using aseptic technique: remove the casirivimab and imdevimab 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 casirivimab and imdevimab vials visually for particulate matter and discoloration prior to administration. should either be observed, the vial must be discarded and replaced with a new vial. the solution for each vial should be clear to slightly opalescent, colorless to pale yellow. obtain a prefilled intravenous infusion bag containing either 50 ml, 100 ml, 150 ml, or 250 ml of either 0.9% sodium chloride injection, usp or 5% dextrose injection, usp. withdraw the appropriate amount of casirivimab and imdevimab from each respective vial(s) and inject into a prefilled infusion bag containing either 0.9% sodium chloride injection, usp or 5% dextrose injection, usp, (see table 1 and table 2 ). if using one vial to prepare more than one infusion bag, then prepare all infusion bags at the same time. the product is preservative-free, therefore do not store unused solution in vial(s). gently invert infusion bag by hand approximately 10 times to mix. do not shake . this product is preservative-free and therefore, the diluted infusion solution should be administered immediately (see table 3 and table 4 ). if immediate administration is not possible, store the diluted casirivimab and imdevimab infusion solution in the refrigerator between 2°c to 8°c (36°f to 46°f) for no more than 36 hours or at room temperature up to 25°c (77°f) for no more than 4 hours. if refrigerated, allow the infusion solution to equilibrate to room temperature for approximately 30 minutes prior to administration. table 1: recommended dilution instructions for 600 mg of casirivimab and 600 mg of imdevimab for intravenous infusion size of prefilled 0.9% sodium chloride or 5% dextrose infusion bag preparing using co-formulated casirivimab and imdevimab vial preparing casirivimab and imdevimab using individual vials 600 mg of casirivimab and 600 mg of imdevimab are added to the same infusion bag and administered together as a single intravenous infusion. 50 ml add 10 ml of co-formulated casirivimab and imdevimab (1 vial) into a prefilled 0.9% sodium chloride or 5% dextrose infusion bag and administer as instructed below add: 5 ml of casirivimab (may use 2 vials of 2.5 ml or 1 vial of 11.1 ml) and 5 ml of imdevimab (may use 2 vials of 2.5 ml or 1 vial of 11.1 ml) and inject into a prefilled 0.9% sodium chloride or 5% dextrose infusion bag and administer as instructed below 100 ml 150 ml 250 ml table 2: recommended dilution instructions for 300 mg of casirivimab and 300 mg of imdevimab for intravenous infusion for repeat dosing subsequent repeat dosing every 4 weeks after initial 600 mg casirivimab and 600 mg imdevimab dosing for the duration of ongoing exposure. size of prefilled 0.9% sodium chloride or 5% dextrose infusion bag preparing using co-formulated casirivimab and imdevimab vial preparing casirivimab and imdevimab using individual vials 300 mg of casirivimab and 300 mg of imdevimab are added to the same infusion bag and administered together as a single intravenous infusion. 50 ml add 5 ml of co-formulated casirivimab and imdevimab into a prefilled 0.9% sodium chloride or 5% dextrose infusion bag and administer as instructed below add: 2.5 ml of casirivimab (may use 1 vial of 2.5 ml or 1 vial of 11.1 ml) and 2.5 ml of imdevimab (may use 1 vial of 2.5 ml or 1 vial of 11.1 ml) and inject into a prefilled 0.9% sodium chloride or 5% dextrose infusion bag and administer as instructed below 100 ml 150 ml 250 ml administration by intravenous infusion casirivimab and imdevimab infusion solution should be administered by a qualified healthcare professional using aseptic technique. gather the recommended materials for infusion: polyvinyl chloride (pvc), polyethylene (pe)-lined pvc, or polyurethane (pu) infusion set in-line or add-on 0.2 micron polyethersulfone (pes) filter attach the infusion set to the intravenous bag. prime the infusion set. administer the entire infusion solution in the bag via pump or gravity through an intravenous line containing a sterile, in-line or add-on 0.2-micron polyethersulfone (pes) filter (see table 3 and table 4 ). due to potential overfill of prefilled saline bags, the entire infusion solution in the bag should be administered to avoid underdosage. the prepared infusion solution should not be administered simultaneously with any other medication. the compatibility of casirivimab and imdevimab injection with intravenous solutions and medications other than 0.9% sodium chloride injection, usp or 5% dextrose injection, usp is not known. after infusion is complete, flush the tubing with either 0.9% sodium chloride injection, usp or 5% dextrose injection, usp to ensure delivery of the required dose. discard unused product. clinically monitor patients during administration and observe patients for at least 1 hour after infusion is complete. table 3: recommended administration rate for 600 mg of casirivimab and 600 mg of imdevimab for intravenous infusion size of prefilled 0.9% sodium chloride or 5% dextrose infusion bag used maximum infusion rate minimum infusion time 50 ml the minimum infusion time for patients administered casirivimab and imdevimab together using the 50 ml prefilled 0.9% sodium chloride or 5% dextrose infusion bag must be at least 20 minutes to ensure safe use. 180 ml/hr 20 minutes 100 ml 310 ml/hr 21 minutes 150 ml 310 ml/hr 31 minutes 250 ml 310 ml/hr 50 minutes table 4: recommended administration rate for 300 mg of casirivimab and 300 mg of imdevimab for intravenous infusion for repeat dosing subsequent repeat dosing every 4 weeks after initial 600 mg casirivimab and 600 mg imdevimab dosing for the duration of ongoing exposure. size of prefilled 0.9% sodium chloride or 5% dextrose infusion bag used maximum infusion rate minimum infusion time 50 ml the minimum infusion time for patients administered casirivimab and imdevimab together using the 50 ml prefilled 0.9% sodium chloride or 5% dextrose infusion bag must be at least 20 minutes to ensure safe use. 165 ml/hr 20 minutes 100 ml 310 ml/hr 20 minutes 150 ml 310 ml/hr 30 minutes 250 ml 310 ml/hr 49 minutes preparation for subcutaneous injection remove the casirivimab and imdevimab vial(s) 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 casirivimab and imdevimab vial(s) visually for particulate matter and discoloration prior to administration. should either be observed, the vial must be discarded and replaced with a new vial. the solution for each vial should be clear to slightly opalescent, colorless to pale yellow. casirivimab and imdevimab should be prepared using the appropriate number of syringes (see table 5 and table 6 ). obtain 3 ml or 5 ml polypropylene luer lock syringes with luer connection and 21-gauge 1½ inch transfer needles. withdraw the appropriate amount of solution into each syringe (see table 5 and table 6 ). prepare all syringes at the same time. replace the 21-gauge transfer needle with a 25-gauge or 27-gauge needle for subcutaneous injection. this product is preservative-free and therefore, the prepared syringes should be administered immediately. if immediate administration is not possible, store the prepared casirivimab and imdevimab syringes in the refrigerator between 2ºc to 8ºc (36ºf to 46ºf) for no more than 24 hours, or at room temperature up to 25ºc (77ºf) for no more than 8 hours. if refrigerated, allow the syringes to equilibrate to room temperature for approximately 20 minutes prior to administration. table 5: preparation of 600 mg of casirivimab and 600 mg of imdevimab for subcutaneous injections prepare 600 mg of casirivimab and 600 mg of imdevimab preparation of 4 syringes using casirivimab and imdevimab co-formulated vial withdraw 2.5 ml solution per syringe into four separate syringes. using casirivimab and imdevimab individual vials casirivimab: withdraw 2.5 ml solution per syringe into two separate syringes. imdevimab: withdraw 2.5 ml solution per syringe into two separate syringes. for total of 4 syringes. table 6: preparation of 300 mg of casirivimab and 300 mg of imdevimab for subcutaneous injections for repeat dosing subsequent repeat dosing every 4 weeks after initial 600 mg casirivimab and 600 mg imdevimab dosing for the duration of ongoing exposure. prepare 300 mg of casirivimab and 300 mg of imdevimab preparation of 2 syringes using casirivimab and imdevimab co-formulated vial withdraw 2.5 ml solution per syringe into two separate syringes. using casirivimab and imdevimab individual vials casirivimab: withdraw 2.5 ml solution into one syringe. imdevimab: withdraw 2.5 ml solution into one syringe. for total of 2 syringes. administration for subcutaneous injection for the administration of 600 mg of casirivimab and 600 mg of imdevimab, gather 4 syringes (see table 5 ) and prepare for subcutaneous injections. for the administration of 300 mg of casirivimab and 300 mg of imdevimab, gather 2 syringes (see table 6 ) and prepare for subcutaneous injections. administer the subcutaneous injections consecutively, each at a different injection site, into the thigh, back of the upper arm, or abdomen, except for 2 inches (5 cm) around the navel. the waistline should be avoided. when administering the subcutaneous injections, it is recommended that providers use different quadrants of the abdomen or upper thighs or back of the upper arms to space apart each 2.5 ml subcutaneous injection of casirivimab and imdevimab. do not inject into skin that is tender, damaged, bruised, or scarred. clinically monitor patients after injections and observe patients for at least 1 hour.

rtion of the trial, subjects were treated with a single intravenous infusion of 600 mg of casirivimab and 600 mg of imdevimab (n=827), or 1,200 mg of casirivimab and 1,200 mg of imdevimab (n=1,849), or 4,000 mg of casirivimab and 4,000 mg of imdevimab (n=1,012), or placebo (n=1,843). regen-cov is not authorized at the 4,000 mg of casirivimab and 4,000 mg of imdevimab dose. the 1,200 mg of casirivimab and 1,200 mg of imdevimab is no longer authorized under this eua [see clinical trial results and supporting data for eua (18) ]. in pooled phase 1/2/3 analysis, infusion-related reactions (adverse event assessed as causally related by the investigator) of grade 2 or higher severity have been observed in 10/4,206 (0.2%) of those who received regen-cov at the authorized dose or a higher dose [see warnings and precautions (5.1) ]. overall, in phase 1/2/3, three subjects receiving the 8,000 mg dose of regen-cov, and one subject receiving the 1,200 mg of casirivimab and 1,200 mg of imdevimab infusion-related reactions (urticaria, pruritus, flushing, pyrexia, shortness of breath, chest tightness, nausea, vomiting, rash) which resulted in permanent discontinuation of the infusion. all events resolved [ see warnings and precautions (5.1) ]. anaphylactic reactions have been reported in the clinical program in subjects receiving regen-cov. the events began within 1 hour of completion of the infusion, and in at least one case required treatment including epinephrine. the events resolved. cov-2069 this is a randomized, double-blind, placebo-controlled clinical trial assessing the efficacy and safety of regen-cov (casirivimab and imdevimab) for post-exposure prophylaxis of covid-19 in household contacts of individuals infected with sars-cov-2. subjects who were sars-cov-2 negative at baseline were enrolled in cohort a and received a single dose of 600 mg of casirivimab and 600 mg of imdevimab subcutaneously (n=1,311) or placebo (n=1,306). adverse events were reported in 265 subjects (20%) in the regen-cov group and 379 subjects (29%) in the placebo group. injection site reactions (all grade 1 and 2) occurred in 55 subjects (4%) in the regen-cov group and 19 subjects (2%) in the placebo group. the most common signs and symptoms of injection site reactions which occurred in at least 1% of subjects in the regen-cov group were erythema and pruritus. hypersensitivity reactions occurred in 2 subjects (0.2%) in the regen-cov group and all hypersensitivity reactions were grade 1 in severity. there were no cases of anaphylaxis. subjects who were sars-cov-2 positive at baseline were enrolled in cohort b and received a single dose of 600 mg of casirivimab and 600 mg of imdevimab subcutaneously (n=155) or placebo (n=156). adverse events were reported in 52 subjects (34%) in the regen-cov group and 75 subjects (48%) in the placebo group. injection site reactions, all of which were grade 1 or 2, occurred in 6 subjects (4%) in the regen-cov group and 1 subject (1%) in the placebo group. the most common signs and symptoms of injection site reactions which occurred in at least 1% of subjects in the regn-cov group were ecchymosis and erythema. there were no cases of hypersensitivity reaction or anaphylaxis. cov-2093 this is a randomized double-blind, placebo-controlled phase 1 trial evaluating the safety, pharmacokinetic and immunogenicity of repeated doses of 600 mg of casirivimab and 600 mg of imdevimab administered subcutaneously in healthy adult subjects. in cov-2093, subjects were randomized 3:1 to regen-cov (n=729) or placebo (n=240) administered every 4 weeks for 24 weeks. adverse events were reported in 380 subjects (52%) in the regen-cov group and 111 subjects (46%) in the placebo group. injection site reactions occurred in 12% and 4% of subjects following single dose administration in the regen-cov and placebo groups, respectively; the remaining safety findings following subcutaneous administration in the regen-cov group were similar to the safety findings observed with intravenous administration of regen-cov in cov-2067. with repeat dosing, injection site reactions occurred in 252 subjects (35%) in the regen-cov group and 38 subjects (16%) in the placebo group; all injection site reactions were grade 1 or 2 in severity. hypersensitivity reactions occurred in 8 subjects (1%) in the regen-cov group; and all hypersensitivity reactions were grade 1 or 2 in severity. there were no cases of anaphylaxis. the authorized dosage for repeat dosing for post-exposure prophylaxis of covid-19 for certain individuals who remain at high risk of exposure for longer than 4 weeks is the initial dose of 600 mg casirivimab and 600 mg imdevimab followed by 300 mg of casirivimab and 300 mg of imdevimab administered every 4 weeks [see dosage and administration (2.2) ] .

in pregnancy (see clinical considerations ). 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 casirivimab and/or imdevimab in human milk or animal milk, the effects on the breastfed infant, or the effects of the drug 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 regen-cov (casirivimab and imdevimab) and any potential adverse effects on the breastfed child from regen-cov 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 regen-cov is not authorized for use in pediatric patients under 12 years of age or weighing less than 40 kg. the safety and effectiveness of casirivimab and imdevimab are being assessed in pediatric and adolescent patients in an ongoing clinical trial. the recommended dosing regimen is expected to result in comparable serum exposures of casirivimab and imdevimab in patients 12 years of age and older and weighing at least 40 kg as observed in adults, since adults with similar body weight have been included in trials cov-2067, cov-2069, and cov-2093. 11.4 geriatric use of the 4,567 subjects with sars-cov-2 infection randomized in trial cov-2067, 14% were 65 years or older, and 4% were 75 years of age or older. of the 3,029 subjects randomized in trial cov-2069, 9% were 65 years or older and 2% were 75 years of age or older. of the 974 subjects randomized in trial cov-2093, 13% were 65 years or older and 2% were 75 years of age or older. the difference in pharmacokinetics (pk) of casirivimab and imdevimab in geriatric patients compared to younger patients is unknown [see clinical trial results and supporting data for eua (18.1) ] . 11.5 renal impairment casirivimab and imdevimab are not eliminated intact in the urine, thus renal impairment is not expected to affect the exposure of casirivimab and imdevimab. 11.6 hepatic impairment the effect of hepatic impairment on pk of casirivimab and imdevimab is unknown. 11.7 other specific populations the effect of other covariates (e.g., sex, race, body weight, disease severity) on pk of casirivimab and imdevimab is unknown.

iderations ). 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.

was identified for regen-cov at all doses, based on viral load and clinical outcomes. similar reductions in viral load (log10 copies/ml) were observed in subjects for the (600 mg of casirivimab and 600 mg of imdevimab) intravenous and (600 mg of casirivimab and 600 mg of imdevimab) subcutaneous doses; however, only limited clinical outcome data are available for the subcutaneous route of administration for the treatment of symptomatic patients. 14.3 pharmacokinetics both casirivimab and imdevimab exhibited linear and dose-proportional pharmacokinetics (pk) between (600 mg of casirivimab and 600 mg of imdevimab) to (4,000 mg of casirivimab and 4,000 mg of imdevimab) doses of regen-cov (casirivimab and imdevimab) following intravenous administration of single dose. a summary of pk parameters after a single (600 mg of casirivimab and 600 mg of imdevimab) intravenous dose, for each antibody is provided in table 7. table 7: summary of pk parameters for casirivimab and imdevimab after a single 600 mg of casirivimab and 600 mg of imdevimab intravenous dose of regen-cov in study cov-2067 pk parameter mean (sd) casirivimab imdevimab c eoi (mg/l) concentration at end of 1-hour infusion 192 (80.9) 198 (84.8) c 28 (mg/l) observed concentration 28 days after dosing, i.e., on day 29, as defined in the protocol 46.2 (22.3) 38.5 (19.7) a summary of pk parameters after a single 600 mg of casirivimab and 600 mg of imdevimab subcutaneous dose is shown in table 8. table 8: summary of pk parameters for casirivimab and imdevimab after a single 600 mg of casirivimab and 600 mg of imdevimab subcutaneous dose of regen-cov pk parameter mean (sd) , mean (sd) concentration at 24 hours (c 24 ) of casirivimab and imdevimab in serum with 1200 sc dosing, 22.5 (11.0) mg/l and 25.0 (16.4) mg/l, respectively casirivimab imdevimab c max (mg/l) 55.6 (22.2) 52.7 (22.5) t max (day) median (range) 8.00 (4.00, 87.0) 7.00 (4.00, 15.0) auc 0-28 (mg∙day/l) 1060 (363) 950 (362) auc inf (mg∙day/l) value reported for subjects with %auc inf extrapolated <20% 2580 (1349) 1990 (1141) c 28 (mg/l) observed concentration 28 days after dosing, i.e., on day 29 30.7 (11.9) 24.8 (9.58) half-life (day) 31.8 (8.35) 26.9 (6.80) for the repeat dose prophylaxis intravenous and subcutaneous regimens, population pharmacokinetic simulations predicted that trough concentrations in serum at steady-state after an initial 600 mg casirivimab and 600 mg imdevimab intravenous or subcutaneous dose followed by monthly (every 4 weeks) 300 mg casirivimab and 300 mg imdevimab intravenous or subcutaneous doses are similar to slightly higher than observed mean day 29 concentrations in serum for a single 600 mg casirivimab and 600 mg imdevimab subcutaneous dose. specific populations the effect of different covariates (e.g., age, sex, race, body weight, disease severity, hepatic impairment) on the pk of casirivimab and imdevimab is unknown. renal impairment is not expected to impact the pk of casirivimab and imdevimab, since mabs with molecular weight >69 kda are known not to undergo renal elimination. similarly, dialysis is not expected to impact the pk of casirivimab and imdevimab. drug-drug interactions casirivimab and imdevimab are mabs which 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 [see drug interactions (10) ] .

s shown in table 8. table 8: summary of pk parameters for casirivimab and imdevimab after a single 600 mg of casirivimab and 600 mg of imdevimab subcutaneous dose of regen-cov pk parameter mean (sd) , mean (sd) concentration at 24 hours (c 24 ) of casirivimab and imdevimab in serum with 1200 sc dosing, 22.5 (11.0) mg/l and 25.0 (16.4) mg/l, respectively casirivimab imdevimab c max (mg/l) 55.6 (22.2) 52.7 (22.5) t max (day) median (range) 8.00 (4.00, 87.0) 7.00 (4.00, 15.0) auc 0-28 (mg∙day/l) 1060 (363) 950 (362) auc inf (mg∙day/l) value reported for subjects with %auc inf extrapolated <20% 2580 (1349) 1990 (1141) c 28 (mg/l) observed concentration 28 days after dosing, i.e., on day 29 30.7 (11.9) 24.8 (9.58) half-life (day) 31.8 (8.35) 26.9 (6.80) for the repeat dose prophylaxis intravenous and subcutaneous regimens, population pharmacokinetic simulations predicted that trough concentrations in serum at steady-state after an initial 600 mg casirivimab and 600 mg imdevimab intravenous or subcutaneous dose followed by monthly (every 4 weeks) 300 mg casirivimab and 300 mg imdevimab intravenous or subcutaneous doses are similar to slightly higher than observed mean day 29 concentrations in serum for a single 600 mg casirivimab and 600 mg imdevimab subcutaneous dose. specific populations the effect of different covariates (e.g., age, sex, race, body weight, disease severity, hepatic impairment) on the pk of casirivimab and imdevimab is unknown. renal impairment is not expected to impact the pk of casirivimab and imdevimab, since mabs with molecular weight >69 kda are known not to undergo renal elimination. similarly, dialysis is not expected to impact the pk of casirivimab and imdevimab. drug-drug interactions casirivimab and imdevimab are mabs which 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 [see drug interactions (10) ] .

mdevimab antibody concentration package size ndc number regen-cov (casirivimab and imdevimab) 600 mg/600 mg per 10 ml (60 mg/60 mg per ml) 1 vial per carton 61755-039-01 individual casirivimab and imdevimab solutions must be administered together. table 13: individual package size antibody concentration package size ndc number casirivimab regn10933 1,332 mg/11.1 ml (120 mg/ml) 1 vial per carton 61755-024-01 300 mg/2.5 ml (120 mg/ml) 1 vial per carton 61755-026-01 imdevimab regn10987 1,332 mg/11.1 ml (120 mg/ml) 1 vial per carton 61755-025-01 300 mg/2.5 ml (120 mg/ml) 1 vial per carton 61755-027-01 each co-packaged carton contains 1 vial of casirivimab and 1 vial of imdevimab. refer to table 14. table 14: casirivimab and imdevimab co-packaged carton co-packaged carton contents co-packaged components concentration co-packaged carton ndc number 2 vials 1 vial of casirivimab (ndc 61755-024-00) 1,332 mg/11.1 ml (120 mg/ml) 61755-042-02 1 vial of imdevimab (ndc 61755-025-00) 1,332 mg/11.1 ml (120 mg/ml) 2 vials 1 vial of casirivimab (ndc 61755-026-00) 300 mg/2.5 ml (120 mg/ml) 61755-045-02 1 vial of imdevimab (ndc 61755-027-00) 300 mg/2.5 ml (120 mg/ml) each regen-cov dose pack contains sufficient number of vials of casirivimab [regn10933] and imdevimab [regn10987] to prepare up to two treatment doses (600 mg of casirivimab and 600 mg of imdevimab). refer to table 15. table 15: dose pack providing 1,200 mg casirivimab and 1,200 mg imdevimab regen-cov dose pack size regen-cov dose pack components concentration regen-cov dose pack ndc number 2 cartons 1 vial of casirivimab regn10933 (ndc 61755-024-01) 1,332 mg/11.1 ml (120 mg/ml) 61755-035-02 1 vial of imdevimab regn10987 (ndc 61755-025-01) 1,332 mg/11.1 ml (120 mg/ml) 8 cartons 4 vials of casirivimab regn10933 (ndc 61755-026-01) 300 mg/2.5 ml (120 mg/ml) 61755-036-08 4 vials of imdevimab regn10987 (ndc 61755-027-01) 300 mg/2.5 ml (120 mg/ml) 5 cartons 1 vial of casirivimab regn10933 (ndc 61755-024-01) 1,332 mg/11.1 ml (120 mg/ml) 61755-037-05 4 vials of imdevimab regn10987 (ndc 61755-027-01) 300 mg/2.5 ml (120 mg/ml) 5 cartons 4 vials of casirivimab regn10933 (ndc 61755-026-01) 300 mg/2.5 ml (120 mg/ml) 61755-038-05 1 vial of imdevimab regn10987 (ndc 61755-025-01) 1,332 mg/11.1 ml (120 mg/ml) storage and handling casirivimab is preservative-free. discard any unused portion. imdevimab is preservative-free. discard any unused portion. store unopened casirivimab and imdevimab vials in a refrigerator at 2°c to 8°c (36°f to 46°f) in the original carton to protect from light. unopened vials may be stored in the original carton at room temperature [up to 25°c (77°f)] and must be used within 30 days. if not used in the 30 days, discard vials. do not freeze. do not shake. do not expose to direct light. solution in vial requires dilution prior to intravenous administration. the prepared infusion solution is intended to be used immediately. if immediate administration is not possible, store diluted casirivimab and imdevimab infusion solution in the refrigerator at 2°c to 8°c (36°f to 46°f) for no more than 36 hours or at room temperature up to 25°c (77°f) for no more than 4 hours. if refrigerated, allow the infusion solution to equilibrate to room temperature for approximately 30 minutes prior to administration. the prepared syringes should be administered immediately. if immediate administration is not possible, store the prepared casirivimab and imdevimab syringes in the refrigerator between 2ºc to 8ºc (36ºf to 46ºf) for no more than 24 hours, or at room temperature up to 25ºc (77ºf) for no more than 8 hours. if refrigerated, allow the syringes to equilibrate to room temperature for approximately 20 minutes prior to administration.

ny 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 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 your other medical conditions to become worse. what is regen-cov (casirivimab and imdevimab)? regen-cov is an investigational medicine used in adults and adolescents (12 years of age and older who weigh at least 88 pounds (40 kg)) who are at high risk for severe covid-19, including hospitalization or death for: treatment of mild to moderate symptoms of covid-19 post-exposure 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 vaccine dose in a 2-dose series [such as the pfizer or moderna vaccines], or 2 weeks after a single-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). regen-cov is investigational because it is still being studied. there is limited information known about the safety and effectiveness of using regen-cov to treat people with covid-19 or to prevent covid-19 in people who are at high risk of being exposed to someone who is infected with sars-cov-2. regen-cov is not authorized for pre-exposure prophylaxis for prevention of covid-19. the fda has authorized the emergency use of regen-cov for the treatment of covid-19 and the post-exposure prevention of covid-19 under an emergency use authorization (eua). for more information on eua, see the " what is an emergency use authorization (eua)? " section at the end of this fact sheet. who should not take regen-cov? do not take regen-cov if you have had a severe allergic reaction to regen-cov. what should i tell my health care provider before i receive regen-cov? tell your healthcare provider about all of your medical conditions, including if you: have any allergies have had a severe allergic reaction including anaphylaxis to regen-cov previously have received a covid-19 vaccine have 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 will i receive regen-cov (casirivimab and imdevimab)? regen-cov consists of two investigational medicines, casirivimab and imdevimab, given together at the same time through a vein (intravenous or iv) or injected in the tissue just under the skin (subcutaneous injections). your healthcare provider will determine the most appropriate way for you to be given regen-cov. treatment: if you are receiving an intravenous infusion, the infusion will take 20 to 50 minutes or longer. your healthcare provider will determine the duration of your infusion. if your healthcare provider determines that you are unable to receive regen-cov as an intravenous infusion which would lead to a delay in treatment, then as an alternative, regen-cov can be given in the form of subcutaneous injections. if you are receiving subcutaneous injections, your dose will be provided as multiple injections given in separate locations around the same time. post-exposure prevention: if you are receiving subcutaneous injections, your dose will be provided as multiple injections given in separate locations around the same time. if you are receiving an intravenous infusion, the infusion will take 20 to 50 minutes or longer. after the initial dose, if your healthcare provider determines that you need to receive additional doses of regen-cov for ongoing protection, the additional intravenous or subcutaneous doses would be administered monthly. what are the important possible side effects of regen-cov (casirivimab and imdevimab)? possible side effects of regen-cov are: allergic reactions. allergic reactions can happen during and after infusion or injection of regen-cov. tell your healthcare provider right away or seek immediate medical attention if you get any of the following signs and symptoms of allergic reactions: 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 your lips, face, or throat, rash including hives, itching, muscle aches, feeling faint, dizziness and sweating. these reactions may be severe or life threatening. worsening symptoms after treatment: you may experience new or worsening symptoms after infusion or injection, including fever, difficulty breathing, rapid or slow heart rate, tiredness, weakness or confusion. if these symptoms occur, contact your healthcare provider or seek immediate medical attention as some of these symptoms have required hospitalization. it is unknown if these symptoms 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. the side effects of getting any medicine by subcutaneous injection may include pain, bruising of the skin, soreness, swelling, and possible infection at the injection site. these are not all the possible side effects of regen-cov. not a lot of people have been given regen-cov. serious and unexpected side effects may happen. regen-cov is still being studied so it is possible that all of the risks are not known at this time. it is possible that regen-cov could interfere with your body's own ability to fight off a future infection of sars-cov-2. similarly, regen-cov may reduce your 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 healthcare provider if you have any questions. what other treatment choices are there? like regen-cov (casirivimab and imdevimab), 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 that are used to treat people with covid-19. your healthcare provider may talk with you about clinical trials you may be eligible for. it is your choice to be treated or not to be treated with regen-cov. should you decide not to receive regen-cov or stop it at any time, it will not change your standard medical care. what other prevention choices are there? vaccines to prevent covid-19 are also available under emergency use authorization. use of regen-cov does not replace vaccination against covid-19. regen-cov is not authorized for pre-exposure prophylaxis for prevention of covid-19. what if i am pregnant or breastfeeding? there is limited experience using regen-cov (casirivimab and imdevimab) in pregnant women or breastfeeding mothers. for a mother and unborn baby, the benefit of receiving regen-cov may be greater than the risk of using the product. if you are pregnant or breastfeeding, discuss your options and specific situation with your healthcare provider. how do i report side effects with regen-cov (casirivimab and imdevimab)? tell your healthcare provider right away if you have any side effect that bothers you or does not go away. report side effects to fda medwatch at www.fda.gov/medwatch or call 1-800-fda-1088 or call 1-844-734-6643. how can i learn more? ask your health care provider. visit www.regencov.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 regen-cov (casirivimab and imdevimab) 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. regen-cov has not undergone the same type of review as an fda-approved product. in issuing an eua under the covid-19 public health emergency, the fda 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 regen-cov 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). manufactured by: regeneron pharmaceuticals, inc. 777 old saw mill river road tarrytown, ny 10591-6707 ©2022 regeneron pharmaceuticals, inc. all rights reserved. revised: 01/2022