remibrutinib

Action and Spectrum

Action:  

Remibrutinib is an orally administered small-molecule inhibitor that targets Bruton’s tyrosine kinase (BTK). This intracellular enzyme is found in mast cells, basophils, B lymphocytes, macrophages, and platelets. BTK plays a key role in cell signaling through the Fc epsilon receptor-1 (FcεR1), Fc gamma receptors (FcγR), and the B cell antigen receptor (BCR). In addition, Remibrutinib blocks other kinases related to BTK, including tec protein tyrosine kinase (TEC) and BMX non-receptor tyrosine kinase (BMX). 

Drug Interaction

Adverse Reaction

Frequency Defined  

Abdominal Pain (3%) 

Nausea 18 (3%)  

Headache (7%)  

Bleeding (9%)  

Nasopharyngitis (11%) 

Black Box Warning

Black Box Warning  

Risk of Bleeding: Patients should be closely monitored for any indications of bleeding. RHAPSIDO treatment should be temporarily stopped if bleeding occurs or around the time of surgical procedures. The use of RHAPSIDO in combination with other antithrombotic medications can heighten the likelihood of bleeding. 

Live Attenuated Vaccines: Live or live-attenuated vaccines should not be administered to individuals undergoing treatment with RHAPSIDO. 

Contraindication / Caution

Contraindication/Caution:  

None 

Pregnancy / Lactation

Pregnancy Warnings:  

Pregnancy category: N/A  

Lactation: Excretion in human breastmilk is unknown  

Pregnancy categories:  

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

Category B: No evidence of risk to fetus found in animal reproduction studies and there are not enough studies on pregnant women.  

Category C: Adverse effects on the fetus found with evidence in animal reproduction studies and no adequate evidence for an effect in humans, care must be taken for potential risks in pregnant women.  

Category D: There is adequate data available with sufficient evidence of human fetal risk from various platforms, but despite potential risks may be used only in emergency cases for potential benefits.  

Category X: Drugs listed in this category clearly outweigh risks over benefits. These category drugs should be prohibited for pregnant women.   

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

Pharmacology

Pharmacology:  

Remibrutinib is an orally administered small-molecule inhibitor that targets Bruton’s tyrosine kinase (BTK). This intracellular enzyme is found in mast cells, basophils, B lymphocytes, macrophages, and platelets. BTK plays a key role in cell signaling through the Fc epsilon receptor-1 (FcεR1), Fc gamma receptors (FcγR), and the B cell antigen receptor (BCR). In addition, Remibrutinib blocks other kinases related to BTK, including tec protein tyrosine kinase (TEC) and BMX non-receptor tyrosine kinase (BMX). 

Pharmacokinetics:  

Absorption  

At steady state, the median time for Remibrutinib to reach maximum plasma concentration (Tmax) is about 1 hour, with a range of 0 to 4 hours. 

Distribution 

In vitro, the blood-to-plasma concentration ratio of Remibrutinib is 0.813. Plasma protein binding is approximately 95.4% and remains independent of concentration. The estimated apparent oral volume of distribution at steady state is 1238 L. 

Metabolism 

Remibrutinib undergoes primary metabolism via the CYP3A4 enzyme. 

Excretion and Elimination 

In healthy volunteers given radiolabeled (14C) Remibrutinib intravenously, about 70% of total radioactivity was recovered in feces (with no unchanged drug detected), while 30% was recovered in urine (2.9% as unchanged Remibrutinib). 

The terminal half-life of Remibrutinib is estimated at 1 to 2 hours, with an apparent oral clearance of about 160 L/hour. 

Adminstartion

Administration:  

The route of administration is oral. 

Patient Information Leaflet

Patient information leaflet  

Generic Name: remibrutinib 

Why do we use remibrutinib?  

Early clinical studies indicate that remibrutinib may help decrease the formation of abscesses and inflammatory nodules.  

Remibrutinib is under investigation as a potential treatment for relapsing–remitting MS, owing to its effects on B cells and immune system regulation.  

Ongoing trials are assessing remibrutinib in conditions such as myasthenia gravis, Sjögren’s syndrome, and chronic inducible urticaria.