- March 15, 2022
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Brand Name :
Rezurock
Synonyms :
belumosudil
Class :
ROCK Inhibitors
Dosage Forms & Strengths
Tablet
200 mg
Graft Versus Host Disease
200 mg orally daily
chronic graft-versus-host disease
200 mg orally daily
Dosage Modifications
Hepatotoxicity
Grade 3 AST: put on hold till recovery of bilirubin, ALT, and AST to Grade 0-1, then start as per suggested dose
Grade 4 AST: discontinue forever
Other adverse reactions
Grade 3: put on hold till recovery to Grade 0-1, then start as per suggested dose
Grade 4: discontinue forever
Renal impairment
Mild-to-moderate: dose modification not required
Severe: study not performed
Patients with pre-existing severe renal impairment: study not performed
Hepatic impairment
Patients with pre-existing severe hepatic impairment: study not performed
Strong CYP3A4 inducers
Raise dose to 200 mg orally two times daily, if co-administered
Proton pump inhibitors
Raise dose to 200 mg orally two times daily, if co-administered
Dosing Considerations
Monitoring parameters
Monitor ALT, total bilirubin and AST once in a month
Dosage Forms & Strengths
Tablet
200 mg
chronic graft-versus-host disease
Safety and efficacy not determined in less than twelve years old
≥12 years: 200 mg orally daily
Dosage Modifications
Hepatotoxicity
Grade 3 AST: put on hold till recovery of bilirubin, ALT, and AST to Grade 0-1, then start as per suggested dose
Grade 4 AST: discontinue forever
Other adverse reactions
Grade 3: put on hold till recovery to Grade 0-1, then start as per suggested dose
Grade 4: discontinue forever
Renal impairment
Mild-to-moderate: dose modification not required
Severe: study not performed
Patients with pre-existing severe renal impairment: study not performed
Hepatic impairment
Patients with pre-existing severe hepatic impairment: study not performed
Strong CYP3A4 inducers
Raise dose to 200 mg orally two times daily, if co-administered
Proton pump inhibitors
Raise dose to 200 mg orally two times daily, if co-administered
Dosing Considerations
Monitoring parameters
Monitor ALT, total bilirubin and AST once in a month
Refer to adult dosing
it may decrease the serum concentration of belumosudil
it may decrease the serum concentration of belumosudil
it may decrease the serum concentration of belumosudil
it may decrease the serum concentration of belumosudil
it may decrease the serum concentration of belumosudil
may diminish the serum concentration when combined with belumosudil
may diminish the serum concentration when combined with belumosudil
may diminish the serum concentration when combined with belumosudil
may diminish the serum concentration when combined with belumosudil
may diminish the serum concentration when combined with belumosudil
belumosudil :they may diminish the serum concentration of CYP3A4 Inducers
belumosudil :they may diminish the serum concentration of CYP3A4 Inducers
belumosudil: they may diminish the serum concentration of antacids
belumosudil: they may diminish the serum concentration of antacids
belumosudil: they may diminish the serum concentration of antacids
belumosudil: they may diminish the serum concentration of antacids
belumosudil: they may diminish the serum concentration of antacids
belumosudil: they may diminish the serum concentration of antacids
belumosudil: they may diminish the serum concentration of antacids
belumosudil: they may diminish the serum concentration of Inhibitors of the Proton Pump
belumosudil: they may diminish the serum concentration of Inhibitors of the Proton Pump
belumosudil: they may diminish the serum concentration of Inhibitors of the Proton Pump
belumosudil: they may diminish the serum concentration of Inhibitors of the Proton Pump
belumosudil: they may diminish the serum concentration of Inhibitors of the Proton Pump
may diminish the serum concentration of CYP3A4 Inducers
may diminish the serum concentration when combined
may diminish the serum concentration of antacids
CYP3A strong enhancers of the small intestine may reduce the bioavailability of belumosudil
it may enhance the risk of side effects when combined with mitomycin
nafcillin will decrease the effect of action of belumosudil by affecting enzyme CYP3A4 metabolism.
the effect of belumosudil is decreased by lorlatinib, by altering intestinal or hepatic CYP3A4 enzyme metabolism
pexidartinib decreases the effect or level of belumosudil by altering the intestinal or hepatic CYP3A4 enzyme metabolism
Actions and Spectrum
belumosudil has been reported to alter immunological response by preventing T-cell activation and immune cell migration. In some conditions when the immune system is not regulated, such as chronic graft-versus-host disease (cGVHD), this regulation of the immune response is advantageous.
In preclinical models, fibrosis—the excessive production of fibrous connective tissue has been found to be decreased by belumosudil. Chronic graft-versus-host disease (cGVHD), a dangerous and sometimes fatal complication that can arise following an allogeneic hematopoietic stem cell transplant, has been the main target of research and development for the drug belumosudil.
Frequency defined
1-10%
Grade 2-4 max post
Potassium increased (7%)
Creatinine increased (4%)
Alkaline phosphate increased (9%)
ALT increased (7%)
Neutrophil count decreased (8%)
Platelets decreased (10%)
Grade 3-4
Viral infection (4%)
Arthralgia (2%)
Bacterial infection (4%)
Hypertension (7%)
Asthenia (4%)
Abdominal pain (1%)
Edema (1%)
Decreased appetite (1%)
Musculoskeletal pain (4%)
Pyrexia (1%)
Nausea (4%)
Hemorrhage (5%)
Dyspnea (5%)
Diarrhea (5%)
Max post:
Calcium decreased (1%)
Hemoglobin decreased (1%)
Phosphate decreased (7%)
ALT increased (2%)
Potassium increased (1%)
Neutrophil count decreased (4%)
Platelets decreased (5%)
>10%
All grades
Edema (27%)
Hemorrhage (23%)
Musculoskeletal pain (22%)
Viral infection (19%)
Hypertension (21%)
Headache (21%)
Arthralgia (15%)
Nasal congestion (12%)
Diarrhea (35%)
Decreased appetite (17%)
Bacterial infection (16%)
Infection (53%)
Pyrexia (18%)
Dyspnea (33%)
Rash (12%)
Pruritus (11%)
Muscle spasm (17%)
Dysphagia (16%)
Cough (30%)
Abdominal pain (22%)
Asthenia (46%)
Nausea (42%)
Grade 0-1 (baseline)
Phosphate decreased (76%)
Lymphocytes decreased (62%)
Potassium increased (82%)
ALT increased (83%)
Platelets decreased (82%)
Hemoglobin decreased (79%)
Gamma glutamyl transferase (GGT) increased (47%)
Alkaline phosphatase increased (80%)
Calcium decreased (82%)
Creatinine increased (83%)
Neutrophil count decreased (83%)
Grade 2-4 max post
Phosphate decreased (28%)
Hemoglobin decreased (11%)
GGT increased (21%)
Calcium decreased (12%)
Lymphocytes decreased (29%)
Grade 3-4
Infection (16%)
Max post:
GGT increased (11%)
Lymphocytes decreased (13%)
Black Box Warning
belumosudil drug does not have any black box warning.
Contraindication/Caution:
Contraindication:
Caution:
Pregnancy warnings:
Pregnancy category: N/A
Lactation: Excretion into human milk is unknown
Pregnancy Categories:
Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester.
<b>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
belumosudil is a selective inhibitor of Rho-associated coiled-coil kinase (ROCK).
belumosudil prevents the ROCK enzymes from working, especially ROCK1 and ROCK2. Serine/threonine kinases known as ROCKs control the actin cytoskeleton’s organization, cellular contractility, and additional cellular functions related to cell migration, immunological response, and fibrosis.
Pharmacodynamics
Actin cytoskeleton organization and cell contractility are controlled by ROCK enzymes.
belumosudil has been demonstrated to modify the immune response by preventing T-cell activation and immune cell migration. This regulation is advantageous in some immune system-dysregulated illnesses.
Pharmacokinetics
Absorption
The oral administration results in good absorption. After dosage, the maximum plasma concentration (Cmax) is typically attained 2 to 4 hours later.
Distribution
The moderate plasma protein binding of belumosudil is around 90%. It has the capacity to spread across the body’s numerous tissues.
Metabolism
Cytochrome P450 (CYP) enzymes, particularly CYP3A4, metabolize belumosudil in the liver. Both active and inactive metabolites are produced by the liver metabolism.
Elimination and excretion
Hepatic metabolism is the primary route of elimination for belumosudil. The precise excretion mechanisms are not fully known.
Administration
belumosudil is available in oral tablet form for administration.
The tablets should not be broken, chewed, or crushed. They should be taken whole with a glass of water.
Patient information leaflet
Generic Name: belumosudil
Why do we use belumosudil?
To treat chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic stem cell transplantation, belumosudil has principally been developed.
After an allogeneic hematopoietic stem cell transplant, cGVHD is a potentially fatal complication that can happen when the donor’s immune cells assault the recipient’s organs and tissues.
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