muromonab CD3

Action and Spectrum

Actions and Spectrum: 

The mechanism of action of muromonab CD3 involves binding to the CD3 receptor on the surface of T-cells, a type of white blood cell involved in immune responses. muromonab CD3 exerts its effects by several mechanisms: 

• T-cell depletion: The binding of muromonab CD3 to the CD3 receptor on T-cells activates the complement system, leading to cell lysis and subsequent elimination of T-cells. This depletion of T-cells reduces their ability to mount an immune response. 
• Blockade of T-cell receptor (TCR) signaling: muromonab CD3 binding to the CD3 receptor interferes with the interaction between the TCR and antigen-presenting cells. This disrupts the normal signaling pathways required for T-cell activation and proliferation. 
• Modulation of cytokine production: muromonab CD3 administration can alter cytokine production patterns. It has been shown to decrease the production of pro-inflammatory cytokines, such as interleukin-2 (IL-2) and interferon-gamma (IFN-γ) while increasing the production of anti-inflammatory cytokines. 

The spectrum of activity of muromonab CD3 is primarily focused on T-cells, specifically targeting and depleting CD3-positive T-cells. It affects CD4-positive (helper) and CD8-positive (cytotoxic) T-cell subsets. By depleting T-cells, muromonab CD3 inhibits cellular-mediated immune responses, including T-cell activation, proliferation, and cytokine release. This broad immunosuppressive effect makes it helpful in preventing organ rejection in solid organ transplantation. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

Chills (59%) 

Nausea/Vomiting (19%) 

Diarrhea (14%) 

Wheezing (13%) 

Pyrexia (90%) 

Dyspnea (21%) 

Chest pain (14%) 

Tremor (13%) 

Headache (11%)  

1-10% 

Anorexia (10%) 

Chest pain (9%) 

HTN (8%) 

Diaphoresis (7%) 

Hyperventilation (7%) 

Pruritis (7%) 

Abd pain (6%) 

Dizziness (6%) 

Abnl chest sound (10%) 

Tachycardia (10%) 

Fatigue (9%) 

Arthralgia (7%) 

GI pain (7%) 

Leukopenia (7%) 

Vasodilation (7%) 

Confusion (6%) 

Depression (2-5%) 

Nervousness (2-5%) 

Somnolence (2-5%) 

Bradycardia (2-5%) 

Malaise (2-5%) 

Pulmonary edema (2-5%) 

Thrombocytopenia (2-5%)  

<1% 

Anaphylaxis (rare) 

Black Box Warning

Black box warning: 

• Allergic Reactions: muromonab CD3 can trigger hypersensitivity reactions, including anaphylaxis, in some individuals. These reactions can be severe and life-threatening. 
• Infections: The immunosuppressive effects of muromonab CD3 can increase the risk of viral, bacterial, and fungal infections.  
• Neurological Effects: muromonab CD3 has been associated with neurological adverse effects, such as seizures, encephalopathy, and altered mental status.  

Contraindication / Caution

Contraindications/caution: 

Contraindications: 

• Hypersensitivity: muromonab CD3 should not be administered to individuals with known hypersensitivity or severe allergic reactions to the medication or its components.  
• Severe or Uncontrolled Infections: The use of muromonab CD3 is contraindicated in patients with severe or uncontrolled infections. Since muromonab CD3 suppresses the immune system, it can increase the risk of infections and worsen existing infections. 
• Preexisting Pulmonary Edema or Congestive Heart Failure: muromonab CD3 should not be used in patients with preexisting pulmonary edema or congestive heart failure. The medication can cause or exacerbate fluid retention, leading to respiratory distress and worsening heart failure symptoms. 
• Seizure Disorders: muromonab CD3 should be used cautiously in patients with a history of seizures or other neurological disorders. The medication has been associated with seizures and can potentially worsen preexisting conditions. 

Caution: 

• Immunosuppression: muromonab CD3 is a potent immunosuppressive agent that can increase infection risk. Patients receiving muromonab CD3 should be monitored closely for signs of infections, and appropriate prophylactic measures may be required. 
• Lymphoproliferative Disorders: Using muromonab CD3 has increased the risk of developing lymphoproliferative disorders, including lymphomas and post-transplant lymphoproliferative disorders (PTLDs).  
• Neurological Effects: muromonab CD3 can cause neurological adverse effects, such as seizures, encephalopathy, and altered mental status.  
• Fluid Retention: muromonab CD3 can lead to fluid retention and worsen preexisting conditions such as pulmonary edema or congestive heart failure.

Pregnancy / Lactation

Pregnancy consideration: Using muromonab CD3 (OKT3) during pregnancy is generally not recommended due to limited safety data. 

Pregnancy Category: C 

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: 

muromonab CD3 binds to the CD3 complex, part of the T-cell receptor (TCR) complex. By binding to CD3, muromonab CD3 activates T-cells and triggers a cascade of immunological events, leading to T-cell depletion and immunosuppression. 

Pharmacodynamics: 

muromonab CD3’s pharmacodynamics result in immunosuppression, primarily targeting T-cell function and reducing the risk of organ rejection in transplantation. 

Pharmacokinetics: 

Absorption 

muromonab CD3 is administered intravenously (IV) and is rapidly and completely absorbed into the bloodstream. 

Distribution 

After administration, muromonab CD3 distributes throughout the body, including lymphoid tissues and organs. It specifically targets and binds to CD3 antigens on T-cells. 

Metabolism 

muromonab CD3 is a protein-based monoclonal antibody and is not extensively metabolized in the body. It undergoes degradation and catabolism by proteolytic enzymes. 

Elimination and Excretion 

The elimination of muromonab CD3 primarily occurs through the reticuloendothelial system, which includes the liver and spleen. The drug is also eliminated through renal excretion. 

Adminstartion

Administration: 

muromonab CD3 should be administered intravenously as an IV push over less than 1 minute. It should not be given via intramuscular injection. 

• Pre-medication with Methylprednisolone and Hydrocortisone: Before the first muromonab CD3 administration, pre-medication with methylprednisolone sodium succinate at 1 mg/kg IV is recommended. Additionally, hydrocortisone sodium succinate at 50-100 mg should be administered 30 minutes after the muromonab CD3 infusion. These pre-medications are strongly recommended to decrease the incidence of reactions to the first dose. 
• Filtration: Each dose of muromonab CD3 should be filtered through a low protein-binding 0.22-micron filter before administration. This step helps ensure the removal of any particulate matter or potential contaminants. 
• Temperature Limit: The patient’s temperature should not exceed 37.8°C (100°F) at the time of muromonab CD3 administration. Monitoring the patient’s temperature is necessary to prevent potential adverse reactions associated with elevated body temperature. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: muromonab CD3 

Why do we use muromonab CD3? 

muromonab CD3 (OKT3) has been used for various indications, primarily immunosuppression and preventing organ rejection in solid organ transplantation.  

• Organ Transplantation: muromonab CD3 was used as an immunosuppressive agent in solid organ transplantation, such as kidney, liver, heart, and lung transplantation. It was administered to prevent the rejection of transplanted organs by suppressing the immune response against the foreign tissue. 
• Treatment of Acute Rejection: muromonab CD3 was sometimes used as a therapeutic option in acute rejection episodes in transplant recipients.  
• Steroid-Resistant Rejection: In some cases where rejection did not respond to corticosteroid treatment, muromonab CD3 was considered an alternative therapy. It was used to modulate the immune response and prevent further rejection. 
• Autoimmune Diseases: Although not a primary indication, muromonab CD3 has been explored in treating certain autoimmune diseases, such as rheumatoid arthritis and type 1 diabetes.