tixagevimab and cilgavimab (Investigational)

Action and Spectrum

Actions and Spectrum: 

Mechanism of Action: 

tixagevimab and cilgavimab are monoclonal antibodies of the IgG1 subclass. They bind to the spike protein’s receptor-binding domain (RBD) on the SARS-CoV-2 virus. Binding to the RBD prevents the virus from attaching to and entering human cells.This mechanism helps to neutralize the virus and limit its ability to cause infection and replication. 

Spectrum of Activity: 

tixagevimab and cilgavimab have been specifically developed to target the spike protein of the SARS-CoV-2 virus. Their activity focuses on preventing and treating COVID-19 caused by the SARS-CoV-2 virus. They have demonstrated efficacy against various concern variants, including the original virus strain and certain mutated strains. 

Drug Interaction

Adverse Reaction

Frequency defined 

1-10% 

Fatigue (4%) 

Cough (3%) 

Headache (6%) 

<1% 

SAEs related to cardiac failure (0.2%) 

Myocardial infarctions (0.2%) 

Arrhythmias (0.1%) 

Cardiomegaly 

Cardiorespiratory arrest 

Black Box Warning

Black box warning: 

None 

Contraindication / Caution

Contraindications/caution: 

Contraindications: 

Hypersensitivity reactions 

Caution: 

• Hypersensitivity Reactions: Monoclonal antibodies can cause allergic or hypersensitivity reactions. It is essential to be cautious if you have a known allergy to any component of tixagevimab, cilgavimab, or other monoclonal antibodies. 
• Infusion-Related Reactions: Some individuals may experience infusion-related reactions during or after the administration of monoclonal antibodies.  
• Immunosuppression: Monoclonal antibodies can affect the immune system and may increase the risk of infections. Precautions should be taken, especially in individuals with a history of immunosuppression or those at higher risk of infections. 
• Interference with Vaccinations: The administration of monoclonal antibodies, including tixagevimab and cilgavimab, may interfere with the efficacy of certain vaccines. 

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: 

tixagevimab and cilgavimab are monoclonal antibodies that target the spike protein of the SARS-CoV-2 virus, which is responsible for viral entry into human cells. Binding to the spike protein’s receptor-binding domain (RBD) blocks the virus’s ability to attach to and enter human cells, effectively neutralizing the virus and preventing further infection and replication. 

Pharmacodynamics: 

• Neutralizing Activity: tixagevimab and cilgavimab have been designed to have potent neutralizing activity against the SARS-CoV-2 virus. Binding to the spike protein prevents the virus from attaching to and entering host cells, thereby reducing viral load and replication. This neutralizing activity is crucial for controlling the infection and reducing the severity of COVID-19 symptoms. 
• Immune Response Modulation: Monoclonal antibodies, including tixagevimab and cilgavimab, can also modulate the immune response to the virus. They may enhance the immune system’s ability to recognize and eliminate the virus by engaging immune cells and activating effector functions such as antibody-dependent cellular cytotoxicity (ADCC) or antibody-dependent cellular phagocytosis (ADCP). 

Pharmacokinetics: 

Absorption 

The bioavailability of tixagevimab is 68.5%, indicating a moderate absorption level. The bioavailability of cilgavimab is 65.8%, indicating a moderate absorption level.  

Distribution 

tixagevimab has a volume of distribution (Vd) of 7.7 L, suggesting it is distributed throughout the body. cilgavimab has a volume of distribution (Vd) of 8.7 L, suggesting it is distributed throughout the body.  

Metabolism 

tixagevimab undergoes catabolic pathways like endogenous IgG. cilgavimab undergoes catabolic pathways like endogenous IgG.  

Elimination and Excretion 

tixagevimab is not likely to undergo renal excretion. The half-life of tixagevimab is 87.9 days, indicating a relatively long duration of action. The clearance of tixagevimab is 0.062 L/day, suggesting a slow elimination rate. 

cilgavimab is not likely to undergo renal excretion. The half-life of cilgavimab is 82.9 days, indicating a relatively long duration of action. The clearance of cilgavimab is 0.074 L/day, suggesting a slow elimination rate. 

Adminstartion

Administration: 

Intramuscular administration 

• A certified healthcare professional must administer the medication. 
• tixagevimab and cilgavimab should be given as two consecutive intramuscular injections.  
• Administer at several injection sites, ideally one in each gluteal muscle, one after the other.  
• Individuals should be clinically monitored following injections for at least 1 hour. 

Storage 

Unopened vials  

To prevent exposure to light, refrigerate at 2 to 8 degrees Celsius (36 to 46 degrees Fahrenheit) in the original carton.  

Discard any leftovers.  

Avoid freezing.

Patient Information Leaflet

Patient information leaflet 

Generic Name: tixagevimab and cilgavimab 

Why do we use tixagevimab and cilgavimab? 

tixagevimab and cilgavimab are monoclonal antibodies that are used in combination therapy for the treatment of COVID-19.  

• Treatment of COVID-19: tixagevimab and cilgavimab are used together as a combination therapy for treating mild to moderate COVID-19 in individuals at high risk of progressing to severe disease. These monoclonal antibodies are specifically indicated for use in patients aged 12 years and older, weighing at least 40 kg, and who have positive results of direct SARS-CoV-2 viral testing. They are typically administered together as a single intravenous infusion. 
• Post-Exposure Prophylaxis: tixagevimab and cilgavimab may also be used for post-exposure prophylaxis in individuals who have been in close contact with someone infected with SARS-CoV-2 and are at high risk of developing severe COVID-19. Post-exposure prevention aims to prevent or reduce the disease’s severity in individuals exposed to the virus.