REZUROCK
Clinical safety rating: caution
Comprehensive clinical and safety monograph for REZUROCK (REZUROCK).
REZUROCK (belumosudil) is a selective Rho-associated coiled-coil containing protein kinase (ROCK2) inhibitor. It inhibits ROCK2-mediated signaling, reducing phosphorylation of signal transducer and activator of transcription 3 (STAT3) and promoting STAT5 phosphorylation, thereby modulating the balance between pro-inflammatory (Th17) and regulatory (Treg) T cells.
| Metabolism | Primarily metabolized by CYP3A4. Minor contributions from CYP2C8, CYP2D6, and UGT1A9. |
| Excretion | Rezurock (belumosudil) is primarily eliminated via feces (90%) and urine (7%) as unchanged drug and metabolites. |
| Half-life | Terminal elimination half-life is approximately 19 hours, supporting once-daily dosing. |
| Protein binding | >99% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Approximately 35.6 L, which is roughly 0.5 L/kg (assuming 70 kg), indicating moderate tissue distribution. |
| Bioavailability | Oral bioavailability is approximately 100% when taken with a high-fat meal; absorption is increased by food. |
| Onset of Action | Clinical effect observed within 4 weeks of starting treatment for chronic graft-versus-host disease. |
| Duration of Action | Continuous once-daily dosing is required to maintain therapeutic effect; duration is indefinite for responding patients. |
| Molecular Weight | 520.6 |
200 mg orally once daily.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (eGFR ≥30 mL/min). Safety and efficacy not established in severe renal impairment (eGFR <30 mL/min) or ESRD. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: reduce dose to 100 mg once daily. Child-Pugh C: not recommended. |
| Pediatric use | Safety and efficacy not established in pediatric patients. |
| Geriatric use | No specific dose adjustment recommended based on age; select dose cautiously due to greater frequency of decreased hepatic, renal, or cardiac function. |
| 1st trimester | Avoid use during first trimester due to teratogenicity risk based on animal studies showing embryo-fetal toxicity and malformations. |
| 2nd trimester | Use only if maternal benefit outweighs fetal risk; limited human data but animal studies indicate potential harm. |
| 3rd trimester | Avoid use near term due to possible neonatal adverse effects; monitor for toxicity if exposure occurs. |
Clinical note
Comprehensive clinical and safety monograph for REZUROCK (REZUROCK).
| Placental transfer | Evidence suggests placental transfer in animals; human data lacking but expected due to low molecular weight and moderate lipophilicity. |
| Breastfeeding | Excretion into human milk unknown, but based on molecular weight and high protein binding, likely present. Consider alternative agents or discontinue breastfeeding due to potential for serious adverse reactions in breastfed infants. |
■ FDA Black Box Warning
No black box warning.
| Serious Effects |
Hypersensitivity to belumosudil or any excipientConcomitant use with strong CYP3A4 inducersPregnancy (based on animal teratogenicity)
| Precautions | Embryo-fetal toxicity: Can cause fetal harm. Advise females of reproductive potential of effective contraception during treatment and for 1 week after the last dose., Adverse reactions: Most common (≥20%) are infections, fatigue, nausea, diarrhea, dyspnea, cough, edema, hemorrhage, abdominal pain, musculoskeletal pain, headache, and hypophosphatemia. |
| Food/Dietary | Avoid grapefruit and grapefruit juice due to potential CYP3A4 inhibition increasing drug exposure. No other significant food interactions reported. |
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| Lactation Rating | L5 - Contraindicated |
| Teratogenic Risk | REZUROCK (belumosudil) is a ROCK2 inhibitor. Based on animal studies and its mechanism of action (inhibition of Rho-associated coiled-coil containing protein kinase 2), there is potential for embryofetal toxicity. In animal reproduction studies, administration of belumosudil to pregnant rats and rabbits during organogenesis resulted in increased post-implantation loss, reduced fetal body weights, and structural abnormalities (including cardiovascular and skeletal malformations) at maternal exposures less than the human exposure at the recommended dose. There are no adequate and well-controlled studies in pregnant women. Therefore, the drug should be avoided during pregnancy unless the potential benefit justifies the potential risk. Use effective contraception during treatment and for at least one week after the last dose. |
| Fetal Monitoring | For pregnant women inadvertently exposed, monitor fetal development with serial ultrasound assessments for growth and anatomy. Check for signs of fetal distress. Perform hepatic function tests (ALT, AST, bilirubin) due to potential hepatotoxicity. Monitor complete blood counts for cytopenias. Also monitor for infections and fluid retention/edema. |
| Fertility Effects | Based on animal studies, belumosudil may impair female and male fertility. In female rats, effects on estrous cycling, decreased corpora lutea, and reduced fertility indices were observed. In male rats, effects on sperm parameters (motility, count) and testicular degeneration were noted. The relevance to human fertility is unknown. |
| Clinical Pearls | REZUROCK (belumosudil) is a ROCK2 inhibitor used for chronic graft-versus-host disease (cGVHD) after failure of at least two prior systemic therapies. Monitor for hepatotoxicity with periodic liver function tests. May cause edema; assess volume status and consider diuretics. Drug-drug interactions: avoid strong CYP3A4 inducers; reduce dose with strong CYP3A4 inhibitors. |
| Patient Advice | Take REZUROCK exactly as prescribed, with or without food. · Avoid grapefruit or grapefruit juice while taking this medication. · Report any signs of liver problems: yellowing skin/eyes, dark urine, abdominal pain. · Notify your doctor if you experience swelling in your legs or ankles. · Tell your healthcare provider about all medications you take, including OTC drugs and herbal supplements. |