TRANSFORM HOW YOU USE DRUG INFORMATION

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

No dosage adjustments are needed.

Casirivimab and imdevimab are investigational neutralizing human immunoglobulin G-1 (IgG1) monoclonal antibodies with activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). They are not an FDA-approved treatment; however, they have been authorized for use under an Emergency Use Authorization (EUA) to treat 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 or hospitalization. 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. Use of the drug in hospitalized patients with COVID-19 who require high flow oxygen or mechanism ventilation may be associated with worsening clinical outcomes.[66127] According to the National Institutes of Health (NIH) COVID-19 treatment guidelines, casirivimab and imdevimab are likely to have the greatest clinical effect in the earliest stages of the infection; however, there are still insufficient data to recommend either for or against the use of casirivimab plus imdevimab in outpatients with mild to moderate COVID-19. The NIH emphasizes that the drug should NOT be considered standard of care, nor should it be used to treat hospitalized patients outside of a clinical trial. Due to the possibility of limited supply, the NIH recommends that health care providers prioritize use of the drug in patients at highest risk for COVID-19 progression and ensure communities most affected by COVID-19 have equitable access to casirivimab and imdevimab.[65314]

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 use under an Emergency Use Authorization (EUA) to treat 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 or hospitalization. Under the 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:

• The option to accept or refuse casirivimab and imdevimab
• The significant known and potential risks and benefits of treatment, and the extent to which such potential risks and benefits are unknown

• Available alternative treatments and the risk and benefits of those alternatives
• The need to continue to self-isolate and use infection control measures (e.g., wear mask, isolate, social distance, avoid sharing personal items, clean and disinfect, frequent hand washing) according to CDC guidelines

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]

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]

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. Spike protein amino acid substitutions in variants showing reduced susceptibility to casirivimab include K417E, Y453F, L455F, F486V, and Q493K. Variants showing reduced susceptibility to imdevimab include K444Q and V445A substitutions. Each variant showing reduced susceptibility to 1 antibody retained susceptibility to the other; all variants retained susceptibility to the combination of casirivimab and imdevimab. In clinical trials, a G446V variant was identified that showed reduced susceptibility to imdevimab of 135-fold; however, susceptibility to casirivimab and the combination of casirivimab and imdevimab was retained. It is possible that resistance-associated variants to casirivimab and imdevimab could have cross-resistance to other monoclonal antibodies targeting the RBD of SAR-CoV-2.[66127]

Casirivimab and imdevimab are administered via intravenous infusion. 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