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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for REZUROCK (REZUROCK).
| Breastfeeding | No data are available on the presence of belumosudil in human milk, its effects on the breastfed infant, or its effects on milk production. Because of the potential for serious adverse reactions in nursing infants, advise women not to breastfeed during treatment with REZUROCK and for at least one week after the last dose. The M/P ratio is unknown. |
| 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. |
■ FDA Black Box Warning
No black box warning.
| Serious Effects |
["None."]
| 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."] |
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| 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. |