siltuximab

Action and Spectrum

Actions and Spectrum 

siltuximab exerts its action by targeting and blocking the activity of a specific protein called interleukin-6 (IL-6). IL-6 is known to play a crucial role in promoting inflammation and immune system responses. By inhibiting IL-6, drug helps to modulate the immune system and reduce excessive inflammation.  

In terms of spectrum, drug primarily targets conditions associated with elevated levels of IL-6, such as Castleman’s disease. It is a rare disorder characterized by abnormal growth of lymphatic cells, leading to enlarged lymph nodes and systemic symptoms. drug is specifically indicated for the treatment of multicentric Castleman’s disease (MCD), a subtype that affects multiple regions of lymph nodes. 

Drug Interaction

Adverse Reaction

Frequency defined  

>10% 

Hyperuricemia (11%) 

Upper respiratory tract infection (26%) 

Increased weight (19%) 

Edema (16-26%) 

Pruritus (28%) 

Abdominal pain/distension (12%) 

Rash (28%) 

1-10% 

Hypotension (4-6%) 

Hypertriglyceridemia (8%) 

Lower respiratory tract infection (8%) 

Oropharyngeal pain (8%) 

Headache (8%) 

Thrombocytopenia (9%) 

Constipation (8%) 

Renal impairment (8%) 

Black Box Warning

Black Box Warning:  

None  

Contraindication / Caution

Contraindication/Caution:  

Hypersensitivity: Individuals who have previously exhibited hypersensitivity reactions or severe allergic responses to drug or any components of the drugs. 

Severe Infections: The drug can suppress the immune system, which may increase the risk of severe infections. Therefore, it is contraindicated in individuals with active severe infections. 

Tuberculosis: drug may exacerbate tuberculosis infections. It is contraindicated in individuals with active tuberculosis. 

Live Vaccines: drug can interfere with the efficacy of live vaccines. Therefore, administration of live vaccines should be avoided during treatment with siltuximab. 

Pregnancy / Lactation

Pregnancy warnings:     

Pregnancy category: AU TGA pregnancy category: C
US FDA pregnancy category: C 

Lactation: Excreted into human milk is unknown 

Pregnancy Categories:         

Category A: Studies that were well-controlled and met expectations revealed no risk to the fetus in either the first or second trimester. 

Category B: There were a lack of studies on pregnant women and no evidence of risk to the fetus in animal experiments.   

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:  

siltuximab is a monoclonal antibody that specifically targets and inhibits the action of interleukin-6 (IL-6), a pro-inflammatory cytokine. 

Pharmacodynamics:  

By blocking IL-6, drug helps to reduce the excessive inflammation seen in MCD, thereby alleviating the symptoms associated with the disease. It can lead to decreased systemic symptoms such as fever, night sweats, fatigue, and weight loss, as well as shrinkage of lymph nodes affected by MCD.   

Pharmacokinetics: 

Absorption 

drug is administered intravenously, which means it is directly infused into the bloodstream. As a result, it is rapidly and completely absorbed. 

Distribution 

drug distributes throughout the body. It binds to its target, interleukin-6 (IL-6), and inhibits its activity. The distribution of drug follows the normal distribution pattern of antibodies, reaching various tissues and organs in the body. 

Metabolism 

Monoclonal antibodies like siltuximab are large proteins and generally do not undergo extensive metabolism. They are primarily broken down by proteolytic enzymes into smaller peptides and amino acids. 

Excretion and elimination 

The drug and its breakdown products are eliminated from the body primarily through renal excretion (urine) and to a lesser extent through feces. The exact elimination half-life of siltuximab may vary between individuals, but it is generally around 18 to 20 days. 

Adminstartion

Administration:  

Dosing: The specific dose of drug will depend on the condition being treated and your individual needs.  

Infusion Process: The drug is administered as an intravenous infusion, meaning it is delivered directly into a vein through an IV line. The infusion duration can vary but typically takes around one hour.

Patient Information Leaflet

Patient information leaflet 

Generic Name: siltuximab 

Why do we use siltuximab?   

Treatment of Castleman’s disease: Castleman’s disease (MCD) among adults who are not infected with human immunodeficiency virus (HIV) or human herpesvirus-8 (HHV-8). MCD is a rare lymphoproliferative disorder characterized by enlarged lymph nodes, fever, and other systemic symptoms. drug helps to reduce the signs and symptoms associated with MCD. 

Off-label use in other cytokine release syndrome (CRS): CRS is a condition characterized by an overactive immune response resulting in the release of large amounts of cytokines, including IL-6. drug has shown promise in managing CRS associated with certain conditions, such as chimeric antigen receptor T-cell (CAR-T) therapy or cytokine storm syndrome. 

Treatment of idiopathic multicentric Castleman disease (iMCD): drug is being investigated for the treatment of iMCD, a subtype of Castleman’s disease with unknown causes. Clinical trials have shown that drug can help improve symptoms and reduce the inflammatory markers associated with iMCD.