NOTE: Casirivimab and imdevimab are NOT authorized for treatment or post-exposure prophylaxis of coronavirus disease 2019 (COVID-19) in geographic regions where infection or exposure is likely to have been caused by a non-susceptible severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant. Omicron SARS-CoV-2 variant has become the dominant variant in the United States; and antiviral resistance data show that casirivimab and imdevimab are unlikely to retain activity against Omicron. The FDA will monitor conditions to determine whether use in a geographic region is consistent with this scope of authorization, referring to available information, including information on variant susceptibility, and CDC regional variant frequency data available at: covid.cdc.gov/covid-data-tracker/#variant-proportions.[65314][66127]
Individuals are deemed to be at high risk for progressing to severe COVID-19 if they meet at least 1 of the following criteria:
In addition, other medical conditions or factors (e.g., race, ethnicity) may also place individual patients at high risk, and authorization of casirivimab and imdevimab under the EUA is not limited to only those medical conditions or factors listed above. Health care providers are advised to consider the benefit-to-risk of an individual patient.[66127]
NOTE: There may be logistical or supply constraints that make it impossible to offer the available therapy to all eligible patients, making patient triage necessary. Health care providers should prioritize their use for patients at highest risk of clinical progression. Information on which individuals might receive the greatest benefit from anti-SARS-CoV-2 therapeutics for treatment or prevention can be obtained from www.covid19treatmentguidelines.nih.gov/therapies/statement-on-patient-prioritization-for-outpatient-therapies. Health care providers are advised to consider the benefit-risk for each individual patient.[65314]
NOTE: The National Institutes of Health (NIH) recommends AGAINST the use of casirivimab and imdevimab for treatment of high-risk, nonhospitalized patients with mild to moderate COVID-19. This recommendation is based on Omicron being the dominant variant in the United States and real-time testing to identify rare, non-Omicron variants not being routinely available. Instead, the NIH recommends using 1 of the following therapeutics[65314]:
NOTE: Casirivimab and imdevimab are not authorized for use in patients who are hospitalized due to COVID-19, who require oxygen therapy for COVID-19, or who require an increase in baseline oxygen flow rate due to COVID-19 if already on chronic oxygen therapy for an underlying condition. Use of the drug in hospitalized patients with COVID-19 who require high flow oxygen or mechanical ventilation may be associated with worsening clinical outcomes.[66127]
The optimal dosing regimen has not yet been established, and the recommended dose may be updated as data from clinical trials become available. Administer 600 mg of casirivimab and 600 mg of imdevimab together as a single intravenous infusion. Administer the infusion as soon as possible after the positive test for SARS-CoV-2 and within 10 days of symptom onset.[66127]
The optimal dosing regimen has not yet been established, and the recommended dose may be updated as data from clinical trials become available. Administer 600 mg of casirivimab and 600 mg of imdevimab together as a single intravenous infusion. Administer the infusion as soon as possible after the positive test for SARS-CoV-2 and within 10 days of symptom onset.[66127] Guidelines in pediatric patients suggest the use of monoclonal antibodies for the treatment of mild to moderate COVID-19 in adolescents at the highest risk of severe disease. Highest risk patients include those with obesity, patients who are severely immunocompromised, and those with medical complexity with respiratory technology dependence. The use of monoclonal antibodies for the treatment of mild to moderate COVID-19 could be considered in adolescents with moderate risk of severe disease based on individualized risk assessment and shared decision-making. Moderate-risk conditions include mild-to-moderately immunocompromised, chronic respiratory conditions, congenital heart disease, and sickle cell disease. Guidelines do not suggest routine use of monoclonal antibodies for treatment in adolescents at lower risk of severe disease (i.e., diabetes, chronic kidney disease).[67381]
The optimal dosing regimen has not yet been established, and the recommended dose may be updated as data from clinical trials become available. Give 600 mg of casirivimab and 600 mg of imdevimab via 4 consecutive subcutaneous injections at different injection sites. Administer the injections as soon as possible after the positive test for SARS-CoV-2 and within 10 days of symptom onset.[66127]
The optimal dosing regimen has not yet been established, and the recommended dose may be updated as data from clinical trials become available. Give 600 mg of casirivimab and 600 mg of imdevimab via 4 consecutive subcutaneous injections at different injection sites. Administer the injections as soon as possible after the positive test for SARS-CoV-2 and within 10 days of symptom onset.[66127] Guidelines in pediatric patients suggest the use of monoclonal antibodies for the treatment of mild to moderate COVID-19 in adolescents at the highest risk of severe disease. Highest risk patients include those with obesity, patients who are severely immunocompromised, and those with medical complexity with respiratory technology dependence. The use of monoclonal antibodies for the treatment of mild to moderate COVID-19 could be considered in adolescents with moderate risk of severe disease based on individualized risk assessment and shared decision-making. Moderate-risk conditions include mild-to-moderately immunocompromised, chronic respiratory conditions, congenital heart disease, and sickle cell disease. Guidelines do not suggest routine use of monoclonal antibodies for treatment in adolescents at lower risk of severe disease (i.e., diabetes, chronic kidney disease).[67381]
NOTE: Post-exposure prophylaxis may be considered in high risk patients who are either not fully vaccinated (i.e., at least 2 weeks after completing the dosing series) OR not expected to mount an adequate immune response to the SARS-CoV-2 vaccination (e.g., immunocompromised condition, immunosuppressive medications) AND 1 of the following:
NOTE: Casirivimab and imdevimab are not authorized for pre-exposure prophylaxis, nor should they be used as a substitute for the COVID-19 vaccines.[66127] [65314]
600 mg casirivimab and 600 mg imdevimab together as a single intravenous infusion. Administer the infusion as soon as possible after exposure to SARS-CoV-2. For individuals who are not expected to mount an adequate immune response to the complete COVID-19 vaccination and have ongoing exposure to SARS-CoV-2 for longer than 4 weeks, repeat dosing may be appropriate. If determined to be appropriate, follow the initial 600 mg casirivimab and 600 mg imdevimab dose with subsequent repeat dosing of 300 mg casirivimab and 300 mg imdevimab by a single intravenous infusion once every 4 weeks for the duration of ongoing exposure.[66127] The National Institutes of Health (NIH) recommends a single prophylactic dose of 600 mg casirivimab and 600 mg imdevimab be administered as soon as possible, and preferably within 7 days of exposure; however, unlike the FDA's Emergency Use Authorization, the NIH states there are insufficient data to recommend either for or against repeated dosing every 4 weeks for those who continue to have high risk exposures.[65314]
600 mg casirivimab and 600 mg imdevimab together as a single intravenous infusion. Administer the infusion as soon as possible after exposure to SARS-CoV-2. For individuals who are not expected to mount an adequate immune response to the complete COVID-19 vaccination and have ongoing exposure to SARS-CoV-2 for longer than 4 weeks, repeat dosing may be appropriate. If determined to be appropriate, follow the initial 600 mg casirivimab and 600 mg imdevimab dose with subsequent repeat dosing of 300 mg casirivimab and 300 mg imdevimab by a single intravenous infusion once every 4 weeks for the duration of ongoing exposure.[66127] Guidelines in pediatric patients recommend considering post-exposure prophylaxis in adolescents with the highest risk of severe disease and who are exposed recently in settings where there is a high risk of transmission such as prolonged indoor exposure without the use of adequate personal protective equipment. Highest risk patients include those with obesity, patients who are severely immunocompromised, and those with medical complexity with respiratory technology dependence.[67381]
600 mg casirivimab and 600 mg imdevimab via subcutaneous injections. Administer the injections as soon as possible after exposure to SARS-CoV-2. For individuals who are not expected to mount an adequate immune response to the complete COVID-19 vaccination and have ongoing exposure to SARS-CoV-2 for longer than 4 weeks, repeat dosing may be appropriate. If determined to be appropriate, follow the initial 600 mg casirivimab and 600 mg imdevimab dose with subsequent repeat dosing of 300 mg casirivimab and 300 mg imdevimab by subcutaneous injections once every 4 weeks for the duration of ongoing exposure.[66127] The National Institutes of Health (NIH) recommends a single prophylactic dose of 600 mg casirivimab and 600 mg imdevimab be administered as soon as possible, and preferably within 7 days of exposure; however, unlike the FDA's Emergency Use Authorization, the NIH states there are insufficient data to recommend either for or against repeated dosing every 4 weeks for those who continue to have high risk exposures.[65314]
600 mg casirivimab and 600 mg imdevimab via subcutaneous injections. Administer the injections as soon as possible after exposure to SARS-CoV-2. For individuals who are not expected to mount an adequate immune response to the complete COVID-19 vaccination and have ongoing exposure to SARS-CoV-2 for longer than 4 weeks, repeat dosing may be appropriate. If determined to be appropriate, follow the initial 600 mg casirivimab and 600 mg imdevimab dose with subsequent repeat dosing of 300 mg casirivimab and 300 mg imdevimab by subcutaneous injections once every 4 weeks for the duration of ongoing exposure.[66127] Guidelines in pediatric patients recommend considering post-exposure prophylaxis in adolescents with the highest risk of severe disease and who are exposed recently in settings where there is a high risk of transmission such as prolonged indoor exposure without the use of adequate personal protective equipment. Highest risk patients include those with obesity, patients who are severely immunocompromised, and those with medical complexity with respiratory technology dependence.[67381]
40 kg or more: 600 mg casirivimab and 600 mg imdevimab IV or subcutaneously.
less than 40 kg: Use not authorized.
40 kg or more: 600 mg casirivimab and 600 mg imdevimab IV or subcutaneously.
less than 40 kg: Use not authorized.
40 kg or more: 600 mg casirivimab and 600 mg imdevimab IV or subcutaneously.
less than 40 kg: Use not authorized.
12 years and weighing 40 kg or more: 600 mg casirivimab and 600 mg imdevimab IV or subcutaneously.
12 years and weighing less than 40 kg: Use not authorized.
1 to 11 years: Use not authorized.
Use not authorized.
Use not authorized.
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
No dosage adjustments are needed.
† Off-label indicationNOTE: Casirivimab and imdevimab are NOT authorized for treatment or post-exposure prophylaxis of coronavirus disease 2019 (COVID-19) in geographic regions where infection or exposure is likely to have been caused by a non-susceptible severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant. Omicron SARS-CoV-2 variant has become the dominant variant in the United States; and antiviral resistance data show that casirivimab and imdevimab are unlikely to retain activity against Omicron. The FDA will monitor conditions to determine whether use in a geographic region is consistent with this scope of authorization, referring to available information, including information on variant susceptibility, and CDC regional variant frequency data available at: covid.cdc.gov/covid-data-tracker/#variant-proportions.[65314][66127]
Casirivimab and imdevimab are investigational neutralizing human immunoglobulin G-1 (IgG1) monoclonal antibodies with activity against SARS-CoV-2. They are not an FDA-approved treatment; however, they have been authorized for emergency use as a treatment for mild to moderate COVID-19 in patients (12 years and older weighing at least 40 kg) with positive SARS-CoV-2 viral testing who are at high risk for progressing to severe COVID-19, including hospitalization or death. They are also authorized for use as post-exposure prophylaxis of COVID-19 in persons (12 years and older weighing at least 40 kg) exposed to SARS-CoV-2 who are at high risk for progressing to severe COVID-19 and are not fully vaccinated or are not expected to mount an adequate immune response to the complete COVID-19 vaccination. They are NOT authorized for treatment of patients who are hospitalized due to COVID-19, who require oxygen therapy for COVID-19, or who require an increase in baseline oxygen flow rate due to COVID-19 if already on chronic oxygen therapy for an underlying condition. Use of these drugs in hospitalized patients with COVID-19 who require high flow oxygen or mechanical ventilation may be associated with worsening clinical outcomes. Additionally, the combination is not authorized for pre-exposure prophylaxis, nor should it be used as a substitute for the COVID-19 vaccines.[66127]
The National Institutes of Health (NIH) COVID-19 guidelines recommend individuals who have recently been exposed to SARS-CoV-2 and have symptoms consistent with COVID-19 be evaluated for SARS-CoV-2 infection.
The use and timing of anti-SARS-CoV-2 antibodies should not be affected by prior exposure to the COVID-19 vaccine.[65314] Similarly, the Centers for Disease Control and Prevention (CDC) state that although some reduction in vaccine-induced antibody titers have been observed in persons who previously received antibody products, the benefits versus risks favor proceeding with vaccination; and thus, COVID-19 vaccination does not need to be delayed following receipt of anti-SARS-CoV-2 antibodies.[66175]
For storage information, see the specific product information within the How Supplied section.
NOTE: Casirivimab and imdevimab are not FDA-approved medications; however, they have been authorized for emergency use as a treatment for mild to moderate COVID-19 in patients with positive SARS-CoV-2 viral testing who are at high risk for progressing to severe COVID-19, including hospitalization or death. They are also authorized for use as post-exposure prophylaxis of COVID-19 in persons exposed to SARS-CoV-2 who are at high risk for progressing to severe COVID-19 and are not fully vaccinated or are not expected to mount an adequate immune response to the complete COVID-19 vaccination. Under the Emergency Use Authorization (EUA), health care providers are required to communicate to the patient, parent, or caregiver information consistent with the "Fact Sheet for Patients, Parents and Caregivers" prior to the patient receiving treatment; such information includes the following:
NOTE: Under the EUA, health care providers are required to report all medication errors and serious adverse events potentially related to casirivimab and imdevimab therapy within 7 calendar days from the onset of the event.[66127]
Preparation and Dilution:
Intravenous Infusion:
Preparation:
Subcutaneous Injection:
The safety of casirivimab and imdevimab has been evaluated in a phase 1/2/3 trial involving non-hospitalized patients with mild to moderate COVID-19, a phase 3 post-exposure prophylaxis trial, and a phase 1 safety and pharmacokinetics trial. In the treatment trial, patients were randomized to receive either a placebo (n = 1,843) or single infusions of casirivimab and imdevimab at the following doses: 600 mg/600 mg (n = 827); 1,200 mg/1,200 mg (n = 1,849); 4,000 mg/4,000 mg (n = 1,012). Note, neither the 1,200 mg/1,200 mg nor the 4,000 mg/4,000 mg dose is not authorized the EUA. Of the patients who received casirivimab and imdevimab at the authorized dose or a higher dose, 0.2% experienced infusion-related reactions that were Severity Grade 2 or higher. Permanent discontinuation of the infusion due to an infusion-related reaction (e.g., urticaria, pruritus, flushing, fever, dyspnea, chest tightness, nausea, vomiting, rash) occurred in 3 patients in the 4,000 mg/4,000 mg group and 1 in the 1,200 mg/1,200 mg group. All events resolved upon treatment discontinuation.[66127]
Anaphylactic or anaphylactoid reactions have been reported in patients treated with casirivimab and imdevimab during the clinical program. These adverse events began within 1 hour of the completed infusion, and at least 1 case required treatment with epinephrine which resolved the event. In clinical trials evaluating the safety of administering casirivimab and imdevimab via subcutaneous injections, hypersensitivity reactions were reported in up to 1% of drug recipients. In all cases, the reactions were Grade 1 or 2 in severity, and there were no reports of anaphylaxis.[66127]
The safety of administering casirivimab and imdevimab via subcutaneous injections was evaluated in a randomized, double-blind, placebo-controlled trial involving healthy adults. In these trial, subjects received repeated subcutaneous doses of either 600 mg casirivimab and 600 mg imdevimab (n = 729) or placebo (n = 240) every 4 weeks for 24 weeks. An evaluation of the data found 12% of subjects receiving casirivimab and imdevimab and 4% of subjects in the placebo group developed an injection site reaction after a single dose. With repeated dosing, the incidence of injection site reactions increased to 35% in the casirivimab and imdevimab group and 16% in the placebo group (all Grade 1 or 2). Of note, the 600 mg/600 mg dose used in the study was higher than the authorized dose for repeated subcutaneous injections (after the initial dose) of 300 mg casirivimab and 300 mg imdevimab. In another trial, subcutaneous doses of casirivimab and imdevimab were administered to subjects as post-exposure prophylaxis. In the post-exposure prophylaxis trial, SARS-CoV-2 negative subjects at baseline (cohort A) were administered either 600 mg casirivimab and 600 mg imdevimab as a single subcutaneous dose (n = 1,311) or placebo (n = 1,306). Injection site reactions (all Grade 1 or 2) were reported in 4% of subjects who received casirivimab and imdevimab and 2% who received the placebo. Occurring in at least 1% of drug recipients, the most common injection site reactions were erythema and pruritus. In cohort B of the post-exposure trial, 155 subjects who were SARS-CoV-2 positive at baseline were administered 600 mg casirivimab and 600 mg imdevimab subcutaneously, while 156 subjects were administered a placebo. In this cohort, injection site reactions (all Grade 1 or 2) were reported in 4% of subjects who received casirivimab and imdevimab and 1% who received the placebo. The most common injection site reactions in this cohort were ecchymosis and erythema (both occurring in at least 1% of drug recipients).[66127]
Monoclonal antibodies, such as casirivimab and imdevimab, may be associated with worsening clinical outcomes when administered to hospitalized patients with COVID-19 who require high flow oxygen or mechanical ventilation. Therefore, the drug is not authorized for use in patients who are hospitalized due to COVID-19, who require oxygen therapy for COVID-19, or who require an increase in baseline oxygen flow rate due to COVID-19 if already on chronic oxygen therapy for an underlying condition.[66127]
Infusion-related reactions have been observed during and for up to 24 hours after treatment with casirivimab and imdevimab; these reactions may be severe or life-threatening. Signs and symptoms of these reactions include fever, chills, nausea, headache, bronchospasms, dyspnea, reduced oxygen saturation, fatigue, arrhythmia exacerbation (e.g., atrial fibrillation, sinus tachycardia, bradycardia), chest pain or discomfort, weakness, altered mental status, hypotension, hypertension, angioedema, throat irritation, rash, urticaria, pruritus, myalgia, dizziness, syncope, and diaphoresis. If an infusion-related reaction develops, consider slowing or stopping the infusion and administer appropriate medications and supportive care. Similarly, serious hypersensitivity reactions, including anaphylaxis, have been observed during and for more than 24 hours after treatment with casirivimab and imdevimab. If signs and symptoms of a clinically significant hypersensitivity reaction or anaphylaxis occur, immediately discontinue treatment and initiate appropriate medications and supportive care.[66127]
There are insufficient data regarding the use of casirivimab and imdevimab during pregnancy to determine a drug-associated risk for major birth defects, miscarriages, or adverse maternal or fetal outcomes. Human immunoglobulin G1 (IgG1) antibodies are known to cross the placental barrier; therefore, casirivimab and imdevimab have the potential to be transferred from the mother to the developing fetus. It is unknown if this potential in utero transfer provides any therapeutic benefit or risk to the fetus. According to the manufacturer, casirivimab and imdevimab should be administered during pregnancy only if the potential benefit outweighs the potential risk for the mother and fetus.[66127] The National Institutes of Health (NIH) COVID-19 treatment guidelines recommend that the drug not be withheld from a pregnant woman at high risk of progressing to severe COVID-19 if the clinician thinks that the potential benefit outweighs potential risk.[65314]
There are no data regarding the presence of casirivimab or imdevimab in human milk, the effects on the breast-fed infant, or the effects on milk production; however, maternal immunoglobulin G (IgG) is known to be present in human milk. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, the potential for viral transmission to SARS-CoV-2-negative infants, and the risk of an untreated or inadequately treated condition. Lactating mothers are advised to follow practices according to clinical guidelines to avoid exposing the infant to COVID-19.[66127] The National Institutes of Health (NIH) COVID-19 treatment guidelines recommend post-exposure prophylaxis with anti-SARS-CoV-2 antibodies not be withheld from lactating women who have been exposed to SARS-CoV-2, especially those with additional conditions that increase their risk of progressing to severe disease. Patients and their health care providers should determine if the potential benefits outweigh the potential risks.[65314] If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, health care providers are encouraged to report the adverse effect to the FDA.
Casirivimab and imdevimab are recombinant human immunoglobulin G-1 (IgG1) monoclonal antibodies used in combination as an antiviral medication to target severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The antibodies bind to non-overlapping epitopes of the spike protein receptor binding domain (RBD) of SARS-CoV-2, which prevents the virus from interacting with the human ACE2 receptor. In Jurkat target cells expressing SARS-CoV-2 spike proteins, the combination of casirivimab plus imdevimab elicited antibody-dependent cell-mediated cytotoxicity (ADCC) with human natural killer (NK) effector cells and antibody-dependent cellular phagocytosis (ADCP) with human macrophages. However, the combination did not mediate complement-dependent cytotoxicity in cell-based assays. The estimated 50% effective concentration (EC50) of casirivimab plus imdevimab in neutralizing SARS-CoV-2 in Vero cells is 0.005 mcg/mL.[66127][66130]
There is a potential for treatment failure due to the development of viral variants that are resistant to the combination of casirivimab and imdevimab. Antiviral resistance data show that casirivimab and imdevimab are unlikely to retain activity against the Omicron SARS-CoV-2 variant (B.1.1.529/BA.1). Health care providers are advised to consider the prevalence of SARS-CoV-2 variants in their area when considering treatment options. Other anti-SARS-CoV-2 antibodies should be considered. In cell culture studies, spike protein amino acid substitutions in variants showing reduced susceptibility to casirivimab alone include K417E (182-fold), K417N (7-fold), K417R (61-fold), Y453F (more than 438-fold), L455F (80-fold), E484K (25-fold), F486V (more than 438-fold), and Q493K (more than 438-fold). Variants showing reduced susceptibility to imdevimab alone include substitutions K444N (more than 755-fold), K444Q (more than 548-fold), K444T (more than 1,033-fold), and V445A (548-fold). Casirivimab and imdevimab together show reduced susceptibility to variants with substitutions K444T (6-fold) and V445A (5-fold). In neutralization assays using VSV VLP pseudotyped with spike protein variants identified in circulating SARS-CoV-2, variants with reduced susceptibility to casirivimab alone included those with substitutions E406D (51-fold), V445T (107-fold), E484Q (19-fold), G485D (5-fold), G476S (5-fold), F486L (61-fold), F486S (more than 715-fold), Q493E (446-fold), Q493R (70-fold), and S494P (5-fold). Variants with reduced susceptibility to imdevimab alone included those with substitutions P337L (5-fold), N439K (463-fold), N439V (4-fold), N440K (28-fold), K444L (153-fold), K444M (1,577-fold), G446V (135-fold), N450D (9-fold), Q493R (5-fold), Q498H (17-fold), and P499S (206-fold). The G476D substitution has a 4-fold impact on casirivimab and imdevimab together. Neutralization data for SARS-CoV-2 variant substitutions identified through global surveillance have found no change in susceptibility (i.e., less than 2-fold reduction) to casirivimab and imdevimab together. The variants and key substitutions are as follows:
It is unknown how these data correlate with clinical outcomes.[66127]
Revision Date: 12/23/2021, 03:13:41 PMCasirivimab and imdevimab are administered together via intravenous infusion or subcutaneous injection. Data regarding the pharmacokinetics of casirivimab and imdevimab are limited; however, the pharmacokinetic profiles are expected to be consistent with the profile of other IgG1 monoclonal antibodies. Casirivimab and imdevimab are not metabolized by cytochrome P450 enzymes, nor are they renally excreted.[66127]
Affected cytochrome P450 isoenzymes: none
Following intravenous administration, casirivimab and imdevimab exhibit linear and dose-proportional pharmacokinetics between doses of 600 mg/600 mg and 4,000 mg/4,000 mg. Immediately after a single 600 mg/600 mg intravenous dose, the mean plasma concentrations for casirivimab and imdevimab were 192 mg/L and 198 mg/L, respectively. The mean concentrations for casirivimab and imdevimab on Day 29 (i.e., 28 days after dosing) were 46.2 mg/L and 38.5 mg/L, respectively. For the repeated dose prophylaxis regimens, population pharmacokinetic simulations predict that serum trough concentrations at steady-state after the initial 600 mg casirivimab and 600 mg imdevimab dose followed by every 4 week doses of 300 mg casirivimab and 300 mg imdevimab are similar to or slightly higher than observed mean Day 29 concentrations for a single 600 mg casirivimab and 600 mg imdevimab subcutaneous dose.[66127]
Following a single subcutaneous dose of 600 mg casirivimab and 600 mg imdevimab, the mean maximum plasma concentrations (Cmax) of 55.6 mg/L and 52.7 mg/L, respectively, were achieved in 8 days (range: 4 to 87 days) for casirivimab and 7 days (range: 4 to 15 days) for imdevimab. Systemic exposures (AUC0-28) were 1,060 mg x day/L for casirivimab and 950 mg x day/L for imdevimab. The observed mean plasma concentrations on Day 29 (i.e., 28 days after dosing) were 30.7 mg/L for casirivimab and 24.8 mg/L for imdevimab. The half-lives of casirivimab and imdevimab after subcutaneous injections were 31.8 days and 26.9 days, respectively. For the repeat dose prophylaxis regimens, population pharmacokinetic simulations predict that serum trough concentrations at steady-state after the initial 600 mg casirivimab and 600 mg imdevimab dose followed by every 4 week doses of 300 mg casirivimab and 300 mg imdevimab are similar to or slightly higher than observed mean Day 29 concentrations for a single 600 mg casirivimab and 600 mg imdevimab subcutaneous dose.[66127]
Monoclonal antibodies with a molecular weight greater than 69 kDa are known not to undergo renal elimination; therefore, renal impairment and dialysis are not expected to impact the pharmacokinetics of casirivimab (145.23 kDa) or imdevimab (144.14 kDa).[66127]
The recommended dosing regimen is expected to result in comparable serum exposures of casirivimab and imdevimab in pediatric patients (12 years and older weighing at least 40 kg) as observed in adults.[66127]
There are insufficient data regarding the use of casirivimab and imdevimab during pregnancy to determine a drug-associated risk for major birth defects, miscarriages, or adverse maternal or fetal outcomes. Human immunoglobulin G1 (IgG1) antibodies are known to cross the placental barrier; therefore, casirivimab and imdevimab have the potential to be transferred from the mother to the developing fetus. It is unknown if this potential in utero transfer provides any therapeutic benefit or risk to the fetus. According to the manufacturer, casirivimab and imdevimab should be administered during pregnancy only if the potential benefit outweighs the potential risk for the mother and fetus.[66127] The National Institutes of Health (NIH) COVID-19 treatment guidelines recommend that the drug not be withheld from a pregnant woman at high risk of progressing to severe COVID-19 if the clinician thinks that the potential benefit outweighs potential risk.[65314]
There are no data regarding the presence of casirivimab or imdevimab in human milk, the effects on the breast-fed infant, or the effects on milk production; however, maternal immunoglobulin G (IgG) is known to be present in human milk. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, the potential for viral transmission to SARS-CoV-2-negative infants, and the risk of an untreated or inadequately treated condition. Lactating mothers are advised to follow practices according to clinical guidelines to avoid exposing the infant to COVID-19.[66127] The National Institutes of Health (NIH) COVID-19 treatment guidelines recommend post-exposure prophylaxis with anti-SARS-CoV-2 antibodies not be withheld from lactating women who have been exposed to SARS-CoV-2, especially those with additional conditions that increase their risk of progressing to severe disease. Patients and their health care providers should determine if the potential benefits outweigh the potential risks.[65314] If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, health care providers are encouraged to report the adverse effect to the FDA.