Bamlanivimab and Etesevimab (Monograph)

Drug class: Monoclonal Antibodies
- SARS-CoV-2-specific Monoclonal Antibody

Medically reviewed by Drugs.com on Jan 16, 2024. Written by ASHP.

Introduction

Antiviral; recombinant human IgG₁ neutralizing monoclonal antibodies specific for SARS-CoV-2 virus; used in a combination regimen.

Uses for Bamlanivimab and Etesevimab

Coronavirus Disease 2019 (COVID-19)

A combined regimen of bamlanivimab and etesevimab being investigated for and has been used for the treatment of COVID-19^{† [off-label]} caused by SARS-CoV-2. Also being investigated and has been used for the prevention of COVID-19^{† [off-label]}.

One of several SARS-CoV-2-specific monoclonal antibodies being evaluated for treatment and prevention of COVID-19.

Although efficacy and safety not definitely established, bamlanivimab and etesevimab are available under an FDA emergency use authorization (EUA) to be administered together for treatment of mild to moderate COVID-19 and for postexposure prophylaxis of COVID-19 in certain individuals at high risk for progression to severe COVID-19, including hospitalization or death.

FDA issued an EUA that permits use of bamlanivimab and etesevimab for treatment of mild to moderate COVID-19 in adults and pediatric patients with positive results of direct SARS-CoV-2 viral testing who are at high risk for progression to severe COVID-19 and/or hospitalization. The EUA requires manufacturers to establish a process for monitoring genomic databases for emergence of global viral variants of SARS-CoV-2 and, if requested by FDA, assess activity of bamlanivimab and etesevimab against any global SARS-CoV-2 variants of interest.

FDA reissued the EUA for bamlanivimab and etesevimab to authorize use for postexposure prophylaxis of COVID-19^{† [off-label]} in adults and pediatric patients, including neonates, who are at high risk for progression to severe COVID-19, including hospitalization or death.

FDA issued the EUA for bamlanivimab and etesevimab for treatment of COVID-19 after concluding that emergency use of the drugs for treatment of COVID-19 met criteria for issuance of an EUA for the following reasons: SARS-CoV-2 can cause a serious or life-threatening disease or condition, including severe respiratory illness; based on the totality of scientific evidence available to FDA, it is reasonable to believe that bamlanivimab and etesevimab administered together may be effective in treating mild to moderate COVID-19 in adults and pediatric patients who have positive results of direct SARS-CoV-2 viral testing and are at high risk for progression to severe COVID-19 and/or hospitalization and, when used under the conditions described in the EUA, known and potential benefits of the drugs outweigh known and potential risks; and there are no adequate, approved, and available alternatives to emergency use of bamlanivimab and etesevimab for treatment of COVID-19 in such patients.

FDA expanded the EUA for bamlanivimab and etesevimab to permit use for postexposure prophylaxis of COVID-19 following exposure to SARS-CoV-2 in susceptible individuals at high risk for progression to severe COVID-19, including hospitalization or death, after concluding that it is reasonable to believe that bamlanivimab and etesevimab may be effective for postexposure prophylaxis in such individuals and, when used under the conditions described in the EUA, known and potential benefits outweigh known and potential risks and there are no adequate, approved, and available alternatives to emergency use of bamlanivimab and etesevimab for postexposure prophylaxis of COVID-19.

When determining appropriate use of bamlanivimab and etesevimab under the EUA for treatment or postexposure prophylaxis of COVID-19, consider the following medical conditions and other factors that may place adults and pediatric patients, including neonates, at higher risk for progression to severe COVID-19: older age (e.g., ≥65 years of age); younger age (e.g., <1 year of age); obesity or being overweight; pregnancy; chronic kidney disease; diabetes mellitus; immunosuppressive disease or immunosuppressive therapy; cardiovascular disease (including congenital heart disease) or hypertension; chronic lung disease (e.g., COPD, moderate to severe asthma, interstitial lung disease, cystic fibrosis, pulmonary hypertension); sickle cell disease; neurodevelopmental disorders (e.g., cerebral palsy) or other conditions that confer medical complexity (e.g., genetic or metabolic syndromes, severe congenital anomalies); or medical-related technological dependence (e.g., tracheostomy, gastrostomy, positive-pressure ventilation not related to COVID-19).

FDA also states use of bamlanivimab and etesevimab under the EUA is not limited only to the medical conditions and factors listed above; other medical conditions and factors (e.g., race or ethnicity) may also place individual patients at high risk for progression to severe COVID-19. Consider the benefits versus risks for the individual patient when making treatment decisions regarding use of FDA-authorized SARS-CoV-2-specific monoclonal antibodies, including bamlanivimab and etesevimab. Additional information on medical conditions and factors associated with increased risk for progression to severe COVID-19 is available at [Web].

Bamlanivimab and etesevimab is not authorized under the EUA for use in patients 2 years of age or older who are hospitalized due to COVID-19; however, the EUA permits for young children (i.e., birth to 2 years of age) who are hospitalized with mild to moderate COVID-19 at the time of treatment to receive bamlanivimab and etesevimab because the reasons or threshold for hospital admission may be different or lower for neonates, young infants, and toddlers with COVID-19 compared to older children and adults. Bamlanivimab and etesevimab is not authorized under the EUA for use in patients regardless of age who require oxygen therapy and/or respiratory support due to COVID-19, or are on chronic oxygen therapy due to an underlying non-COVID-19-related comorbidity and require an increase in baseline oxygen flow rate and/or respiratory support due to COVID-19. Benefit not studied in patients hospitalized due to COVID-19; SARS-CoV-2-specific monoclonal antibodies may be associated with worse clinical outcomes when administered to hospitalized COVID-19 patients requiring high-flow oxygen or mechanical ventilation.

If a patient is hospitalized for reasons other than COVID-19 (e.g., an elective orthopedic procedure) and reports mild to moderate symptoms of COVID-19, confirmed with positive results of a direct SARS-CoV-2 viral test, FDA states that treatment with bamlanivimab and etesevimab may be appropriate if the patient is also at high risk for progression to severe COVID-19 and/or hospitalization for COVID-19 and terms and conditions of the EUA are met.

Bamlanivimab and etesevimab is authorized under the EUA for postexposure prophylaxis of COVID-19 (PEP) in adults and pediatric patients, including neonates, who are at high risk for progression to severe COVID-19, including hospitalization or death, and are exposed to an individual infected with SARS-CoV-2 under the following circumstances: the exposed individual is not considered fully vaccinated against COVID-19 or the exposed individual is not expected to mount an adequate immune response to a complete COVID-19 vaccination series (e.g., because of immunocompromising condition or immunosuppressive therapy) and the exposure to an individual infected with SARS-CoV-2 was consistent with CDC's definition of close contact or there is high risk of ongoing exposure to an individual infected with SARS-CoV-2 because of SARS-CoV-2 infection in other individuals in the same institutional setting (e.g., nursing homes, prisons).

Postexposure prophylaxis with bamlanivimab and etesevimab is not a substitute for vaccination against COVID-19.

Bamlanivimab and etesevimab is not authorized for preexposure prophylaxis (PrEP) for prevention of COVID-19.

The EUA requires that bamlanivimab and etesevimab be administered by a health care provider in an appropriate setting and administered together as soon as possible following exposure to SARS-CoV-2 using the dosages recommended in the EUA. (See Dosage and Administration.)

The EUA for bamlanivimab and etesevimab authorizes that distribution of the drugs will be controlled by the US government for use consistent with the terms and conditions of the EUA. (See Restricted Distribution under Preparations.)

The EUA currently authorizes use of bamlanivimab and etesevimab only in US states, territories, and jurisdictions where the combined frequency of SARS-CoV-2 variants resistant to bamlanivimab and etesevimab administered together is ≤5%, as determined by FDA. Consult FDA website at [Web] for information on US states, territories, and jurisdictions where FDA has determined that use of bamlanivimab and etesevimab together is or is not authorized. When considering use of bamlanivimab and etesevimab for treatment or prevention of COVID-19, review patient's travel and contact history within 2 weeks prior to infection or exposure to SARS-CoV-2. (See General under Dosage and Administration.)

To mitigate risks of these unapproved drugs, the EUA includes certain mandatory requirements (including providing information to the patient or parent/caregiver and ensuring that all medication errors and serious adverse events potentially attributable to the drugs are reported to FDA). (See EUA Requirements for Patient Monitoring and Mandatory FDA MedWatch Reporting under Cautions.)

Consult bamlanivimab and etesevimab EUA letter of authorization ([Web]), EUA fact sheet for health care providers ([Web]), and EUA fact sheet for patients, parents, and caregivers ([Web]) for additional information.

Based on data available to date, the National Institutes of Health (NIH) COVID-19 Treatment Guidelines Panel recommends the use of SARS-CoV-2-specific monoclonal antibody therapy for the treatment of mild to moderate COVID-19 in outpatients at high risk of clinical progression as defined by the EUA criteria. Prior to mid-December 2021, bamlanivimab plus etesevimab, casirivimab plus imdevimab, and sotrovimab were the only therapies recommended by the Panel for outpatients with mild to moderate COVID-19 who are at high risk of progression to severe disease. Current recommendations for treating outpatients take into account the high prevalence of the B.1.1.529 (Omicron) variant of concern (VOC). The Omicron VOC is predicted to have markedly reduced susceptibility to bamlanivimab plus etesevimab and casirivimab plus imdevimab. The Panel favors the use of ritonavir-boosted nirmatrelvir in most high-risk outpatients with mild to moderate COVID-19. If ritonavir-boosted nirmatrelvir is unavailable or cannot be used because of drug interactions, the Panel recommends using sotrovimab in patients who live in areas with a high prevalence of the Omicron VOC. If sotrovimab is unavailable, the Panel recommends using a 3-day course of remdesivir. Molnupiravir should only be administered when the ritonavir-boosted nirmatrelvir, sotrovimab, and remdesivir are either not available or cannot be used.

In outpatients (ambulatory patients) with mild to moderate COVID-19 at high risk of progression to severe COVID-19, IDSA suggests use of SARS-CoV-2-specific monoclonal antibody therapy rather than no SARS-CoV-2-specific monoclonal antibody therapy, and recommends selection of the most appropriate SARS-CoV-2-specific monoclonal antibody therapy based on in vitro susceptibility data available for locally circulating SARS-CoV-2 variants.

Bamlanivimab and Etesevimab Dosage and Administration

General

• Circulating SARS-CoV-2 viral variants may be associated with reduced susceptibility to bamlanivimab and etesevimab (see Actions and Spectrum). FDA EUA for bamlanivimab and etesevimab authorizes use only in US states, territories, and jurisdictions where the combined frequency of SARS-CoV-2 variants resistant to bamlanivimab and etesevimab administered together is ≤5%. Consult FDA website at [Web] for information on US states, territories, and jurisdictions where FDA has determined that use of bamlanivimab and etesevimab together is or is not authorized. Information on SARS-CoV-2 viral variants circulating in the US collected through CDC's national genomic surveillance program is available at [Web] and may help guide treatment decisions regarding use of alternative SARS-CoV-2-specific monoclonal antibody therapy when bamlanivimab and etesevimab cannot be used.

• Must be administered to patients in an appropriate setting in which health care providers have immediate access to medications to treat a severe infusion reaction, such as anaphylaxis, and the ability to activate the emergency medical system (EMS) as necessary.

• Must clinically monitor patient during IV infusion of bamlanivimab and etesevimab and observe patient for at least 1 hour after completion of the infusion. (See Sensitivity and Infusion-related Reactions under Cautions.)

• Advise patients who receive bamlanivimab and etesevimab for treatment or postexposure prophylaxis of COVID-19 to continue to self-isolate and use infection control measures (e.g., wear mask, isolate, socially distance, avoid sharing personal items, clean and disinfect “high touch” surfaces, wash hands frequently) according to CDC guidelines.

• Information for clinicians and infusion sites of care administering bamlanivimab and etesevimab to outpatients under the EUA, including recommendations for planning and implementation and considerations for resources and equipment, may be available from the manufacturer or US Health and Human Services (HHS) Office of the Assistant Secretary for Preparedness and Response (ASPR).

Administration

IV Administration

Administer bamlanivimab and etesevimab together only by IV infusion. Do not use bamlanivimab or etesevimab alone as monotherapy.

For administration of bamlanivimab and etesevimab in adults (regardless of weight) and pediatric patients weighing ≥40 kg, bamlanivimab and etesevimab solutions must be diluted together in 0.9% sodium chloride prior to IV infusion.

Under the EUA, pediatric doses of bamlanivimab and etesevimab for pediatric patients <18 years of age and weighing <40 kg do not need to be diluted.

For solution and drug compatibility information, see Compatibility under Stability.

Do not administer simultaneously through same IV infusion line with other drugs.

After IV infusion is completed, flush infusion line with 0.9% sodium chloride injection to ensure delivery of entire dose.

Preparation of Diluted Solution Containing Bamlanivimab and Etesevimab

Bamlanivimab and etesevimab are each supplied as solutions in separate vials; must combine drugs prior to IV infusion.

For administration of bamlanivimab and etesevimab in adults (regardless of weight) and pediatric patients weighing ≥40 kg, dilute the drugs together in 0.9% sodium chloride prior to IV infusion.

Remove one single-dose vial of bamlanivimab solution (700 mg/20 mL [35 mg/mL]) and 2 single-dose vials of etesevimab solution (700 mg/20 mL [35 mg/mL]) from refrigerated storage (see Storage under Stability) and allow to equilibrate to room temperature for approximately 20 minutes before preparing the combined dilution for IV infusion.

Do not shake the vials. Both bamlanivimab and etesevimab should appear as clear to opalescent and colorless to slightly yellow to slightly brown solutions.

To prepare the combined dilution of bamlanivimab and etesevimab for adults and pediatric patients weighing ≥40 kg, dilute the solutions in a 50-, 100-, 150-, or 250-mL prefilled, polyvinyl chloride (PVC) or polyethylene (PE)-lined PVC IV infusion bag containing 0.9% sodium chloride injection. Withdraw 20 mL of bamlanivimab solution (700 mg of bamlanivimab) from a vial and withdraw 20 mL of etesevimab solution from each of 2 separate vials (total of 40 mL; 1.4 g of etesevimab) and transfer into the IV bag containing 0.9% sodium chloride. Gently invert bag by hand approximately 10 times; do not shake.

Administer the combined bamlanivimab and etesevimab solution immediately following dilution. If immediate administration not possible, may store combined diluted solution for up to 7 hours at room temperature (20–25°C) or for up to 24 hours in a refrigerator (2–8°C), including infusion time. If combined diluted solution was refrigerated, allow it to equilibrate to room temperature for approximately 20 minutes prior to administration; do not expose to direct heat.

Use a PVC or PE-lined PVC infusion set to administer the combined bamlanivimab and etesevimab diluted solution. Use of an inline or add-on 0.2- or 0.22-µm polyethersulfone (PES) filter is strongly recommended.

Closed system transfer devices (CSTDs), elastomeric pumps, and pneumatic transport not evaluated for use with bamlanivimab and etesevimab.

Bamlanivimab and etesevimab contain no preservatives; discard any unused solution remaining in vials and any combined diluted solution of the drugs. If the IV infusion is discontinued because of an infusion reaction (see Sensitivity and Infusion-related Reactions under Cautions), discard any unused portion.

Preparation of Undiluted Solution Containing Bamlanivimab and Etesevimab

For administration of bamlanivimab and etesevimab in pediatric patients <18 years of age and weighing <40 kg, the drugs are combined and administered undiluted by IV infusion.

To prepare the combined infusion solution of bamlanivimab and etesevimab for pediatric patients weighing <40 kg, withdraw the appropriate dose of each drug from each vial into a disposable syringe or empty infusion bag (see Table 1). Gently invert syringe or IV bag; do not shake or vigorously agitate.

Under the EUA, single-dose vials may be used to prepare multiple doses; however, all doses should be prepared at the same time and labeled appropriately with the patient weight, dose, and time of preparation. Any unused portion should be discarded.

Rate of Administration

Adults (regardless of weight) and pediatric patients weighing ≥40 kg: Depending on size of prefilled IV infusion bag used to prepare combined diluted bamlanivimab and etesevimab solution, administer by IV infusion over at least 21–70 minutes via pump or gravity. (See Table 2.)

The minimum infusion time for patients weighing ≥40 kg and <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.

Pediatric patients weighing <40 kg: Undiluted IV infusions of bamlanivimab and etesevimab should be administered over at least 16 minutes via pump or gravity. (See Table 3.)

Dosage

Pediatric Patients

Coronavirus Disease 2019 (COVID-19)† [off-label]

Treatment of Mild to Moderate COVID-19† [off-label]

IV

FDA EUA that permits use for treatment of mild to moderate COVID-19 (see Coronavirus Disease 2019 [COVID-19] under Uses) states that pediatric patients weighing ≥40 kg who are outpatients at high risk for progressing to severe COVID-19, including hospitalization or death, should receive 700 mg of bamlanivimab and 1.4 g of etesevimab administered together as a single IV infusion.

The FDA EUA that permits use of bamlanivimab and etesevimab for the treatment of mild to moderate COVID-19^† states that the dosage in pediatric patients weighing <40 kg will vary depending on weight. (See Table 4.)

Administer as soon as possible after positive results of direct SARS-CoV-2 viral testing and within 10 days of symptom onset.

Prevention of Coronavirus Disease 2019 (COVID-19)†

IV

FDA EUA that permits use for postexposure prophylaxis of COVID-19 states that pediatric patients weighing ≥40 kg at high risk for progressing to severe COVID-19, including hospitalization or death, who were exposed to an individual with SARS-CoV-2 infection under the circumstances specified in the EUA (see Coronavirus Disease 2019 [COVID-19] under Uses) should receive 700 mg of bamlanivimab and 1.4 g of etesevimab administered together as a single IV infusion.

The FDA EUA that permits use of bamlanivimab and etesevimab for postexposure prophylaxis of COVID-19^† states that the dosage in pediatric patients weighing <40 kg will vary depending on weight. (See Table 5.)

Administer as soon as possible following exposure to SARS-CoV-2.

Adults

Coronavirus Disease 2019 (COVID-19†)

Treatment of Mild to Moderate COVID-19†

IV

FDA EUA that permits use for treatment of mild to moderate COVID-19 (see Coronavirus Disease 2019 [COVID-19] under Uses) states that adults who are outpatients at high risk for progressing to severe COVID-19, including hospitalization or death, should receive 700 mg of bamlanivimab and 1.4 g of etesevimab administered together as a single IV infusion.

Administer as soon as possible after positive results of direct SARS-CoV-2 viral testing and within 10 days of symptom onset.

Prevention of Coronavirus Disease 2019 (COVID-19)†

IV

FDA EUA that permits use for postexposure prophylaxis of COVID-19 states that adults at high risk for progressing to severe COVID-19, including hospitalization or death, who were exposed to an individual with SARS-CoV-2 infection under the circumstances specified in the EUA (see Coronavirus Disease 2019 [COVID-19] under Uses) should receive 700 mg of bamlanivimab and 1.4 g of etesevimab administered together as a single IV infusion.

Administer as soon as possible following exposure to SARS-CoV-2.

Prescribing Limits

Pediatric Patients

Coronavirus Disease 2019† (COVID-19)

IV

Single dose. Repeat dosing not evaluated.

Adults

Coronavirus Disease 2019† (COVID-19)

IV

Single dose. Repeat dosing not evaluated.

Special Populations

Hepatic Impairment

Mild hepatic impairment: Dosage adjustment not needed.

Moderate or severe hepatic impairment: Not studied.

Renal Impairment

Dosage adjustment not needed.

Geriatric Patients

Dosage adjustment not needed.

Cautions for Bamlanivimab and Etesevimab

Contraindications

• None.

• Must not use in patients with known hypersensitivity to any ingredient in the preparation. (See Sensitivity and Infusion-related Reactions under Cautions.)

Warnings/Precautions

Sensitivity and Infusion-related Reactions

Serious hypersensitivity reactions, including anaphylaxis, reported.

Infusion-related reactions reported during and up to 24 hours after IV infusion; such reactions may be severe or life-threatening. Signs and symptoms of infusion-related reactions may include fever, difficulty breathing, reduced oxygen saturation, chills, fatigue, arrhythmias (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, or diaphoresis.

At least one case of anaphylaxis and other cases of serious infusion-related reactions reported in ongoing clinical trials evaluating bamlanivimab with or without etesevimab; the infusion was stopped and the reactions resolved after appropriate treatment. All such reactions required treatment, including use of epinephrine in at least one patient. Hypersensitivity reactions occurring >24 hours after administration of bamlanivimab and etesevimab reported with use under the EUA.

If signs and symptoms of anaphylaxis or other clinically important hypersensitivity reaction occur, immediately discontinue bamlanivimab and etesevimab IV infusion and initiate appropriate medications and/or supportive care.

If an infusion-related reaction occurs, slow or stop bamlanivimab IV infusion and initiate appropriate medications and/or supportive care.

Clinical Worsening after Bamlanivimab and Etesevimab Administration

Clinical worsening of COVID-19, including signs or symptoms of fever, hypoxia or increased respiratory difficulty, arrhythmias (e.g., atrial fibrillation, sinus tachycardia, bradycardia), fatigue, and altered mental status, reported following administration of bamlanivimab and etesevimab; hospitalization required in some cases. It is not known if these events were related to the drug or occurred because of progression of COVID-19.

Limitations of Benefit and Potential for Risk in Patients with Severe COVID-19

Not authorized for use under the EUA in patients 2 years of age or older who are hospitalized due to COVID-19 and in patients who require oxygen therapy and/or respiratory support due to COVID-19, or are on chronic oxygen therapy due to an underlying non-COVID-19-related comorbidity and require an increase in baseline oxygen flow rate and/or respiratory support due to COVID-19.

Bamlanivimab and etesevimab not studied in patients hospitalized due to COVID-19. SARS-CoV-2-specific monoclonal antibodies, such as bamlanivimab and etesevimab, may be associated with worse clinical outcomes when administered to hospitalized COVID-19 patients requiring high-flow oxygen or mechanical ventilation.

EUA Requirements for Patient Monitoring and Mandatory FDA MedWatch Reporting

Safety and efficacy not established. FDA issued an EUA that permits use of bamlanivimab and etesevimab administered together for treatment of mild to moderate COVID-19^† or postexposure prophylaxis of COVID-19^† in certain adults and pediatric patients with mild to moderate COVID-19 using the dosages recommended in the EUA. (See Coronavirus Disease 2019 [COVID-19] under Uses.)

Only limited data available to date regarding adverse effects associated with use of bamlanivimab and etesevimab. Serious and unexpected adverse events may occur that have not been previously reported with use of the drugs together.

Completion of FDA MedWatch forms to report all medication errors and all serious adverse events potentially related to bamlanivimab and etesevimab is mandatory. Consult FDA fact sheet for health care providers that is provided with the drugs and available at FDA website for requirements and instructions regarding reporting of adverse reactions and medication errors.

Specific Populations

Pregnancy

Data insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Estimated background risk of major birth defects and miscarriage related to COVID-19 unknown; however, disease-associated maternal and/or embryofetal 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.

Use during pregnancy only if potential benefit outweighs potential risk for the woman and fetus. Dosage adjustment not recommended if used in pregnant women.

NIH panel states do not withhold SARS-CoV-2-specific monoclonal antibody therapy from a pregnant woman who has a condition that poses a high risk of progression to severe COVID-19 if clinician determines that potential benefits of such therapy outweigh potential risks.

Nonclinical reproductive toxicity studies not performed. In a tissue cross-reactivity study with bamlanivimab and etesevimab using human fetal tissues, no binding of clinical concern was detected for either drug. Human IgG₁ antibodies are known to cross the placenta; therefore, bamlanivimab and etesevimab have potential to be transferred from the pregnant woman to developing fetus. Not known whether such potential placental transfer provides any treatment benefit or risk to the developing fetus.

Lactation

Not known whether bamlanivimab or etesevimab distributes into human or animal milk, has effects on breast-fed infant, or affects milk production. Maternal IgG is known to be present in human milk.

Consider the developmental and health benefits of breast-feeding along with the mother’s clinical need for bamlanivimab and etesevimab and any potential adverse effects on the breast-fed child from the drugs or from the underlying maternal condition. Dosage adjustment not recommended if used in breast-feeding women.

Women with COVID-19 who are breast-feeding should follow clinical guidelines to avoid exposing the infant to the virus.

Pediatric Use

FDA EUA permits use of bamlanivimab and etesevimab for treatment of mild to moderate COVID-19^† or postexposure prophylaxis of COVID-19^† in certain pediatric patients, including neonates (see Coronavirus Disease 2019 [COVID-19] under Uses).

FDA EUA of bamlanivimab and etesevimab for treatment and postexposure prophylaxis in younger pediatric patients, including neonates, supported by safety and efficacy data in adolescents and adults, in addition to pharmacokinetic and safety data from the BLAZE-1 trial in pediatric patients 10 months to 18 years of age with mild to moderate COVID-19. Dose pediatric patients weighing <40 kg based on body weight. Safety is similar in pediatric patients and adults.

Children were not enrolled in the BLAZE-2 trial evaluating bamlanivimab and etesevimab for postexposure prophylaxis of COVID-19.

Geriatric Use

Data from an ongoing clinical trial in outpatients with mild to moderate COVID-19 (BLAZE-1) indicate 30% of the 1141 patients treated with bamlanivimab and etesevimab were ≥65 years of age and 10% were ≥75 years of age. Based on population pharmacokinetic analyses, there is no difference in pharmacokinetics of the drugs in geriatric patients compared with younger patients.

Hepatic Impairment

Mild hepatic impairment: Based on a population pharmacokinetic analysis, no difference in pharmacokinetics of bamlanivimab and etesevimab compared with patients with normal hepatic function.

Moderate or severe hepatic impairment: Not studied.

Renal Impairment

Not expected to affect bamlanivimab or etesevimab exposure; the drugs not eliminated by renal excretion.

Common Adverse Effects

Data from ongoing clinical trials in outpatients with mild to moderate COVID-19 (BLAZE-1, BLAZE-4) indicate that the most common treatment-emergent adverse events in those treated with bamlanivimab and etesevimab (EUA-authorized dosage or higher) include nausea, dizziness, and pruritus. No treatment-emergent adverse events occurred in >1% of trial participants; rate of adverse events in bamlanivimab and etesevimab treatment groups was comparable to that reported in the placebo groups.

Drug Interactions

Not metabolized by CYP isoenzymes and not renally excreted; interactions unlikely if used concomitantly with drugs that are substrates, inducers, or inhibitors of CYP isoenzymes or with drugs that are renally excreted.

Specific Drugs

Bamlanivimab and Etesevimab Pharmacokinetics

Absorption

Plasma Concentrations

Pharmacokinetic profiles of bamlanivimab and etesevimab are linear and dose proportional following IV infusion of single doses ranging from 700 mg to 7 g.

No change in pharmacokinetics of bamlanivimab or etesevimab administered alone or together, suggesting no interaction between the drugs.

No change in pharmacokinetics of etesevimab between mild to moderate ambulatory patients and healthy individuals.

Bamlanivimab: No differences in pharmacokinetics between ambulatory patients with mild to moderate COVID-19 and hospitalized patients with moderate to severe COVID-19.

Etesevimab: No differences in pharmacokinetics between ambulatory patients with mild to moderate COVID-19 and healthy individuals.

Bamlanivimab: Following single 700-mg dose given by IV infusion over 1 hour, mean peak concentration was 196 mcg/mL; the drug was quantifiable for at least 29 days (mean concentration 22 mcg/mL on day 29).

Etesevimab: Following single 1.4-g dose given by IV infusion over 1 hour, mean peak concentration was 504 mcg/mL; the drug was quantifiable for at least 29 days (mean concentration 111 mcg/mL on day 29).

In a phase 2 trial evaluating regimens ranging from 700 mg of bamlanivimab and 1.4 g of etesevimab to 2.8 g of bamlanivimab and 2.8 g of etesevimab (4 and 2 times the authorized doses of the drugs, respectively) in patients with mild to moderate COVID-19, a flat exposure-response relationship for efficacy was identified using clinical data and pharmacokinetic/pharmacodynamic modeling.

Distribution

Extent

Not known whether bamlanivimab or etesevimab distribute into human or animal milk.

Elimination

Metabolism

Bamlanivimab and etesevimab expected to be degraded into small peptides and component amino acids in a similar manner as endogenous IgG antibodies.

Not metabolized by CYP isoenzymes.

Elimination Route

Not eliminated by renal excretion.

Half-life

Bamlanivimab: Mean apparent terminal elimination half-life is 17.6 days.

Etesevimab: Mean apparent terminal elimination half-life is 25.1 days.

Special Populations

Pediatric patients: Pharmacokinetics of bamlanivimab and etesevimab has been evaluated in 88 pediatric patients <18 years of age receiving weight-based dosing. Weight-based dosing in pediatric patients provides comparable plasma exposures to those observed in adults receiving bamlanivimab 700 mg and etesevimab 1.4 g. EUA-recommended dosage for pediatric patients weighing ≤12 kg is predicted to result in similar exposures when compared to exposures achieved in adults receiving bamlanivimab 700 mg and etesevimab 1.4 g based on pharmacokinetic modeling and simulation.

Hepatic impairment: Based on population pharmacokinetic analysis, no significant differences in pharmacokinetics of bamlanivimab and etesevimab in mild hepatic impairment; moderate or severe hepatic impairment not studied.

Renal impairment: Not expected to affect bamlanivimab or etesevimab exposure.

Based on a population pharmacokinetic analysis, bamlanivimab and etesevimab pharmacokinetics not affected by age, sex, race, or disease severity. In adults with COVID-19, body weight within range of 41–173 kg had no clinically relevant effect on pharmacokinetics of either drug.

Stability

Storage

Parenteral

Injection Solution, for IV Infusion

Bamlanivimab and etesevimab are each supplied as solutions in separate vials.

Vials containing bamlanivimab solution and vials containing etesevimab solution: Refrigerate (2–8°C); store in original cartons to protect from light. Do not freeze, shake, or expose to direct heat.

FDA has authorized an extension to the expiration date of unopened vials of both bamlanivimab and etesevimab that have been properly stored. Confirm the expiration date of unopened vials of bamlanivimab and etesevimab by batch number at the FDA EUA website. If the batch number on the vial or carton is not included on the website, follow the expiration date printed on the vial or carton.

Diluted solution containing bamlanivimab and etesevimab: If immediate administration not possible, may store in a refrigerator (2–8°C) for up to 24 hours or at room temperature (20–25°C) for up to 7 hours, including infusion time.

Undiluted solution containing bamlanivimab and etesevimab: If immediate administration not possible, may store in a refrigerator (2–8°C) for up to 24 hours or at room temperature (20–25°C) for up to 7 hours, including infusion time.

Compatibility

Parenteral

Solution Compatibility1

Actions and Spectrum

• Bamlanivimab (IgG₁) and etesevimab (IgG₁) are SARS-CoV-2-specific recombinant human monoclonal antibodies; produced using a Chinese hamster ovary (CHO) cell line.

• Bamlanivimab and etesevimab bind to different, but overlapping, epitopes of the spike protein receptor-binding domain (RBD) of SARS-CoV-2 and block attachment of the spike protein to the human angiotensin-converting enzyme 2 (ACE2) receptor, thereby preventing the virus from entering cells and inhibiting viral replication. Using both drugs together is expected to reduce risk of viral resistance.

• Neutralizing activity against SARS-CoV-2 demonstrated in vitro in Vero E6 cells. In a dose-response model quantifying plaque reduction using cultured Vero E6 cells, bamlanivimab, etesevimab, and 1:1 ratio of the drugs together neutralized the USA/WA/1/2020 isolate of SARS-CoV-2 with estimated 50% effective concentrations (EC₅₀s) of 0.02 mcg/mL, 0.14, and 0.02 mcg/mL, respectively.

• In female Rhesus macaques, single IV dose of bamlanivimab administered for prophylaxis 24 hours prior to SARS-CoV-2 inoculation resulted in up to a 4 log₁₀ decrease in viral load (genomic RNA) and viral replication (subgenomic RNA) in bronchoalveolar lavage samples compared with control animals, but had less effect on viral RNA in throat and nasal swabs. Applicability of these findings to prophylaxis or treatment in humans not known.

• In male Rhesus macaques, prophylactic or therapeutic administration of etesevimab resulted in approximately 4 or 3 log₁₀ average decreases, respectively, in viral genomic RNA in oropharyngeal swabs at day 4 following infection relative to control animals. Applicability of these findings to prophylaxis or treatment in humans not known.

• There is a potential risk of treatment failure due to development of viral variants resistant to bamlanivimab and/or etesevimab.

• In vitro studies using serial passage of SARS-CoV-2 and directed evolution of the spike protein identified amino acid substitutions in the spike protein RBD that resulted in reduced susceptibility to bamlanivimab (E484D/K/Q, F490S, Q493R, and S494P) and identified substitutions that resulted in reduced susceptibility to etesevimab (K417N, D420N, and N460K/S/T). All variants maintained susceptibility to bamlanivimab and etesevimab together, with the exception of those with E484D, E484K, E484Q, and Q493R substitutions.

• Genotypic and phenotypic testing is ongoing to monitor for potential bamlanivimab and etesevimab resistance-associated spike variations in clinical trial participants. Analysis of baseline samples for 2246 clinical trial participants indicated that 8.4% were infected with SARS-CoV-2 viral variants with reduced susceptibility to either bamlanivimab or etesevimab as predicted by pseudotyped virus-like particles (VLP) or authentic SARS-CoV-2 neutralization assays; no trial participants were infected with a variant predicted to have reduced susceptibility to both bamlanivimab and etesevimab.

• Global surveillance is ongoing to evaluate currently circulating SARS-CoV-2 variants for potential resistance to SARS-CoV-2-specific monoclonal antibodies, including bamlanivimab and etesevimab.

• Data to date from in vitro neutralization assays using pseudotyped VLPs indicate that bamlanivimab and etesevimab together retained activity (<5-fold reduced susceptibility) against a SARS-CoV-2 variant of the B.1.1.7 lineage (Alpha; first detected in UK) and related pseudotyped VLP expressing the spike protein found in the B.1.1.7 variant. Bamlanivimab and etesevimab together retained activity (<5-fold reduced susceptibility) against the B.1.617.2 lineage (Delta; first detected in India) and related pseudotyped VLPs; however, B.1.617.2 sublineages AY.1/AY.2 (commonly known as Delta plus; first detected in India) had 1235-fold reduced susceptibility to bamlanivimab and etesevimab together and the drugs are unlikely to be active against variants in this lineage. SARS-CoV-2 recombinant virus containing the L452R substitution present in B.1.427/B.1.429 lineages (Epsilon; first detected in California) showed 9-fold reduced susceptibility to bamlanivimab and etesevimab together; pseudotyped VLPs expressing spike protein from the B.1.526 lineage (Iota; first detected in New York) and B.1.617.1 lineage (Kappa; first detected in India) showed 30-fold and 6-fold reduced susceptibility, respectively, to bamlanivimab and etesevimab together; and pseudotyped VLPs expressing the full-length spike protein from the C.37 lineage (Lambda; first detected in Peru) had <5-fold reduced susceptibility to bamlanivimab and etesevimab. However, data from pseudotyped VLP neutralization assays indicated that the B.1.351 lineage (Beta; first detected in South Africa), P.1 lineage (Gamma; first detected in Brazil), B.1.621 lineage (Mu; first detected in Colombia), and B.1.1.529/BA.1 lineage (Omicron; first detected in South Africa) had 431-fold, 252-fold, 116-fold, 2,938-fold reduced susceptibility, respectively, to bamlanivimab and etesevimab together and the drugs are unlikely to be active against variants in these lineages.

• Data to date from in vitro neutralization assays using authentic SARS-CoV-2 variant virus indicate that bamlanivimab and etesevimab together retained activity (<5-fold reduced susceptibility) against B.1.1.7 (Alpha; first detected in UK) and B.1.617.2/AY.3 (Delta; first detected in India). Authentic SARS-CoV-2 neutralization assays also indicated that B.1.351 (Beta; first detected in South Africa), B.1.427/B.1.429 (Epsilon; first detected in California), and B.1.526 (Iota; first detected in New York) had >325-fold, 11-fold, and 11-fold reduced susceptibility, respectively, to bamlanivimab and etesevimab together.

• Unclear how small reductions in susceptibility to bamlanivimab and etesevimab identified in vitro using authentic or recombinant SARS-CoV-2 or pseudotyped VLP assays correlate with clinical outcomes.

• Although clinical impact not known, bamlanivimab and etesevimab resistance-associated variants could have cross-resistance to other SARS-COV-2-specific monoclonal antibodies that target the RBD of the virus.

Advice to Patients

• The Fact Sheet for Patients, Parents, and Caregivers: Emergency Use Authorization (EUA) of Bamlanivimab and Etesevimab for Coronavirus Disease 2019 (COVID-19), available at [Web], must be provided to patients or parent/caregivers prior to administration of bamlanivimab and etesevimab.

• Inform patients or parent/caregivers that FDA authorized the emergency use of bamlanivimab and etesevimab, which is an investigational drug regimen that has not received FDA approval, for treatment of mild to moderate COVID-19 or for postexposure prophylaxis of COVID-19 in certain adults and pediatric patients who are at risk for progressing to severe COVID-19, including hospitalization or death.

• Inform patients or parent/caregivers that they have the option to accept or refuse bamlanivimab and etesevimab.

• Provide patients or parent/caregivers with information on available alternative treatments and the risks and benefits of those alternatives, including clinical trials.

• Inform patients or parent/caregivers about the significant known and potential risks and benefits of bamlanivimab and etesevimab, and the extent to which such risks and benefits are unknown.

• Advise patients who receive bamlanivimab and etesevimab for treatment or postexposure prophylaxis of COVID-19 that they should continue to self-isolate and use infection control measures (e.g., wear mask, isolate, socially distance, avoid sharing personal items, clean and disinfect “high touch” surfaces, and wash hands frequently) according to CDC guidelines.

• Importance of informing clinicians of any history of allergies or serious illnesses.

• Importance of immediately reporting any allergic reactions that occur during or after receiving bamlanivimab and etesevimab (e.g., fever, chills, nausea, headache, shortness of breath, low or high BP, rapid or slow heart rate, chest discomfort or pain, weakness, confusion, tiredness, wheezing, rash including urticaria, pruritus, muscle aches, dizziness, sweating, swelling of the lips, face, or throat) and reporting any new or worsening COVID-19 symptoms (e.g., fever, difficulty breathing, rapid or slow heart rate, tiredness, weakness, confusion) to clinicians.

• Importance of informing clinicians if patient has received a COVID-19 vaccine. Advise patients that bamlanivimab and etesevimab does not replace vaccination against COVID-19.

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and herbal supplements.

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Bamlanivimab and etesevimab are not commercially available. FDA issued an EUA for bamlanivimab and etesevimab that allows combined use of the drugs for treatment of mild to moderate COVID-19^† or for postexposure prophylaxis of COVID-19^† in certain adults and pediatric patients who are outpatients at high risk for progression to severe COVID-19, including hospitalization or death. Allocation of bamlanivimab and etesevimab for use under the EUA is being directed by the HHS Office of the Assistant Secretary for Preparedness and Response (ASPR) in collaboration with state and territorial health departments and the manufacturer. Consult ASPR website at for information regarding distribution of bamlanivimab and etesevimab.

Although bamlanivimab was previously available under an FDA EUA for use alone (monotherapy), the EUA for use of bamlanivimab alone was revoked on April 16, 2021. Healthcare facilities that have existing supplies of bamlanivimab (without etesevimab) distributed prior to revocation of the EUA for use of the drug alone can obtain etesevimab to pair with their existing supplies of bamlanivimab for use under the EUA for bamlanivimab and etesevimab.

The EUA for bamlanivimab and etesevimab administered together does not permit use in US states, territories, and jurisdictions where the combined frequency of SARS-CoV-2 variants resistant to bamlanivimab and etesevimab is >5%. Consult FDA website at [Web] for information on US states, territories, and jurisdictions where FDA has determined that use of bamlanivimab and etesevimab together is or is not authorized.

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