Rezurock Belumosudil Mesylate Tablets

1. Indications and Usage
Chronic Graft-versus-Host Disease (cGVHD):
Indicated for the treatment of adult and pediatric patients 12 years of age and older with chronic graft-versus-host disease (cGVHD) after failure of two or more prior lines of systemic therapy.
2. Dosage and Administration
Route of Administration:
For Oral Use ONLY. Swallow tablets whole; do not cut, crush, or chew.
Recommended Dosage:
Standard Dose: 200 mg once daily.
Dose Adjustment (Drug Interactions): Increase dose to 200 mg twice daily when administered with strong CYP3A inducers (e.g., rifampin) or proton pump inhibitors (PPIs) [e.g., omeprazole, rabeprazole].
Administration Instructions:
Take with Food: Must be taken with food to ensure adequate absorption (bioavailability increases approximately 2-fold when taken with food).
Dose Interruption/Modification:
Dosage should be interrupted or modified for severe adverse reactions (e.g., severe infections, hepatotoxicity) until recovery to Grade 1 or baseline.
3. Mechanism of Action
ROCK2 Inhibition:
Belumosudil is a potent and selective inhibitor of ROCK2 (IC50 ~100 nM).
Immunomodulation:
ROCK2 is a negative regulator of the transcription factor FoxP3. By inhibiting ROCK2, belimumab increases the expression of FoxP3, thereby promoting the differentiation and function of regulatory T cells (Tregs) while decreasing the differentiation of Th17 cells. This rebalances the immune system (increasing Tregs/Th17 ratio) and reduces inflammation and fibrosis associated with cGVHD.
4. Safety and Warnings
Hepatotoxicity:
Elevations in ALT, AST, and bilirubin have been observed. Monitor liver function tests at least monthly.
Infections:
Immunosuppression may increase the risk of bacterial, fungal, and viral infections. Monitor for signs of infection.
Hypertension:
Hypertension has been reported. Monitor blood pressure regularly.
Embryo-Fetal Toxicity:
Based on its mechanism, can cause fetal harm. Pregnancy testing should be considered for females of reproductive potential.
5.Adverse Reactions
Most Common (Incidence ≥20%):
Fatigue, diarrhea, nausea, dyspnea, cough, pyrexia, edema, hemorrhage, abdominal pain, musculoskeletal pain, headache, decreased血 phosphorus, increased GGT, lymphopenia, and hypertension.
6.Drug Interactions
Strong CYP3A Inducers:
Significantly decrease belumosudil exposure. Dose increase to twice daily is recommended.
Proton Pump Inhibitors (PPIs):
Significantly decrease belumosudil exposure due to pH dependency. Dose increase to twice daily is recommended.
Immunosuppressants:
Concomitant use with calcineurin inhibitors (e.g., tacrolimus, sirolimus) requires therapeutic drug monitoring as belumosudil may act as a P-gp inhibitor.
7.Pharmaceutical Information
Chemical Composition:
Active Ingredient: Belumosudil Mesylate.
Available Strength: 200 mg tablets.
Appearance: Yellow, oval, film-coated tablets debossed with “KDM” on one side and “200” on the other.
Storage: Store at 25°C (77°F); excursions permitted to 15°C–30°C (59°F–86°F).