bamlanivimab and etesevimab

Action and Spectrum

Actions and Spectrum:

The mechanism of action of bamlanivimab and etesevimab involves binding specifically to the spike protein of SARS-CoV-2 and blocking its ability to interact with the human ACE2 receptor, which is the primary receptor that the virus uses to enter human cells. This prevents the virus from attaching and entering human cells, inhibiting its ability to replicate and spread throughout the body.

bamlanivimab and etesevimab have complementary mechanisms of action, as they target different epitopes, or specific regions, on the spike protein. This dual targeting approach is intended to reduce the risk of viral escape mutations, where the virus mutates in a way that allows it to evade the effects of a single monoclonal antibody. By targeting multiple epitopes, the combination of bamlanivimab and etesevimab is designed to provide a broader spectrum of activity against different variants of SARS-CoV-2.

The spectrum of activity of bamlanivimab and etesevimab includes several variants of SARS-CoV-2, including those with mutations in the spike protein, such as the B.1.1.7 variant (first identified in the UK), the B.1.351 variant (first identified in South Africa), and the P.1 variant (first identified in Brazil), among others. However, the effectiveness of bamlanivimab and etesevimab against different variants may vary. It is essential to consult the latest clinical guidelines and data for the most up-to-date information on their spectrum of activity.

Drug Interaction

Adverse Reaction

Frequency defined

1-10%

Infusion-related reactions (1.1%)

<1%

Nausea (<1%)

Pruritus (<1%)

Dizziness (<1%)

Anaphylaxis (0.07%)

Black Box Warning

Black box warning:

None

Contraindication / Caution

Contraindications/caution:

Contraindications:

None

Caution:

• Emergency Use Authorization (EUA): bamlanivimab and etesevimab currently have Emergency Use Authorization (EUA) from regulatory agencies, such as the U.S. Food and Drug Administration (FDA), for the treatment of mild to moderate COVID-19 in specific populations. This means that their safety and effectiveness are still being evaluated and only approved for regular use in the EUA.
• Appropriate Patient Selection: bamlanivimab and etesevimab are intended for use in specific populations, including those who have tested positive for SARS-CoV-2 and are at high risk for progression to severe COVID-19, such as individuals aged 12 years and older weighing at least 40 kg, with positive results of direct SARS-CoV-2 testing, and who are positive for SARS-CoV-2 testing.
• Allergic Reactions: There have been reports of allergic reactions, including anaphylaxis (a severe and potentially life-threatening allergic reaction), associated with using bamlanivimab and etesevimab.
• Interference with SARS-CoV-2 Testing: bamlanivimab and etesevimab are monoclonal antibodies that may interfere with some laboratory tests used to detect SARS-CoV-2, potentially leading to false-negative results. Patients should inform their healthcare providers about their recent use of bamlanivimab and etesevimab if undergoing SARS-CoV-2 testing.
• Drug Interactions: bamlanivimab and etesevimab may interact with other medications, and concomitant use with other monoclonal antibodies or COVID-19 treatments should be avoided unless specifically recommended by a healthcare provider.
• Limited Evidence: While bamlanivimab and etesevimab have shown efficacy in certain populations and against specific variants of SARS-CoV-2, the evidence regarding their safety and effectiveness in other populations, such as pregnant or breastfeeding individuals or in combination with other treatments, is limited.

Pregnancy / Lactation

Pregnancy consideration: Insufficient data available

Lactation: Excretion of the drug in human breast milk is unknown

Pregnancy category:

Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester.

Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women.

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.

Category N: There is no data available for the drug under this category

Pharmacology

Pharmacology:

The pharmacology of bamlanivimab and etesevimab involves their specific binding to the spike protein of SARS-CoV-2, preventing viral entry into human cells and reducing viral replication and spread.

Pharmacodynamics:

The pharmacodynamics of bamlanivimab and etesevimab involve their specific binding to the spike protein of SARS-CoV-2, which is essential for viral entry into human cells. By binding to the spike protein, these monoclonal antibodies prevent the virus from attaching to the human ACE2 receptor, which is necessary for viral entry. This neutralizing activity reduces the ability of the virus to replicate and spread in the body, thereby reducing the severity of COVID-19 symptoms and the risk of hospitalization.

bamlanivimab and etesevimab have complementary mechanisms of action, as they target different epitopes or specific regions on the spike protein of SARS-CoV-2. This dual targeting approach is intended to reduce the risk of viral escape mutations, where the virus mutates in a way that allows it to evade the effects of a single monoclonal antibody.

The pharmacodynamics of bamlanivimab and etesevimab have been studied in clinical trials. These monoclonal antibodies can reduce viral load and improve clinical outcomes in patients with mild to moderate COVID-19. However, their effectiveness against different variants of SARS-CoV-2 may vary, and it is essential to consult the latest clinical guidelines and data for the most up-to-date information on their spectrum of activity.

Pharmacokinetics:

Absorption

bamlanivimab and etesevimab are administered intravenously, which means they are directly infused into the bloodstream. As such, they are fully absorbed and bioavailable upon administration.

Distribution

Both bamlanivimab and etesevimab are distributed in the extracellular fluid and can potentially penetrate tissues to reach the sites of infection. They are large molecules and are expected to have limited tissue penetration compared to small-molecule drugs.

Metabolism

bamlanivimab and etesevimab are monoclonal antibodies and are not metabolized traditionally. Proteolytic enzymes break them down into smaller peptides or amino acids, which are eliminated from the body.

Elimination and Excretion

bamlanivimab and etesevimab are eliminated primarily through renal excretion, with most of the dose excreted unchanged in the urine. The elimination half-life of bamlanivimab is approximately 18 days, while the elimination half-life of etesevimab is approximately 21 days.

Adminstartion

Administration:

bamlanivimab and etesevimab are monoclonal antibodies administered together as a combination therapy for treating COVID-19.

The recommended dosage and administration of bamlanivimab and etesevimab may vary depending on the specific guidelines and protocols established by the local health authorities or treating physicians. However, a typical administration process for bamlanivimab and etesevimab may involve the following steps:

• Patient Selection: Patients who are eligible for treatment with bamlanivimab and etesevimab usually have tested positive for SARS-CoV-2, the virus that causes COVID-19, and have mild to moderate symptoms. Patients must meet specific criteria, such as age, weight, and risk factors, as determined by their healthcare provider.
• Intravenous Infusion: bamlanivimab and etesevimab are usually administered together as an intravenous infusion. The infusion is typically given over a specified period, which may vary depending on the specific dosing regimen prescribed by the healthcare provider. The infusion is typically done using an intravenous catheter or cannula, and the patient is closely monitored for any adverse reactions or side effects during the infusion.
• Post-Infusion Observation: After the infusion is completed, patients are usually observed for some time, typically for at least one hour, to monitor for any adverse reactions or side effects.

Follow-up Care: Patients who receive bamlanivimab and etesevimab will typically require follow-up care as determined by their healthcare provider. This may include monitoring for any potential side effects or adverse reactions and ongoing management of COVID-19 or other underlying medical conditions.

Patient Information Leaflet

Patient information leaflet

Generic Name: bamlanivimab and etesevimab

Why do we use bamlanivimab and etesevimab?

bamlanivimab and etesevimab are monoclonal antibodies used together as a combination therapy for treating COVID-19. They are authorized for emergency use in the United States by the U.S. Food and Drug Administration (FDA) for the treatment of mild to moderate COVID-19 in certain patients who are at high risk for progression to severe disease or hospitalization.

The authorized uses of bamlanivimab and etesevimab in combination are as follows:

• Treatment of Mild to Moderate COVID-19: bamlanivimab and etesevimab are used together as a treatment option for patients who have tested positive for SARS-CoV-2, the virus that causes COVID-19, and who have mild to moderate symptoms but are at high risk for progression to severe disease or hospitalization.

Emergency Use Authorization (EUA): bamlanivimab and etesevimab have been authorized for emergency use by the FDA under an Emergency Use Authorization (EUA), which allows for their use during the COVID-19 pandemic based on available data and the determination that the potential benefits of using the medications outweigh the risks.