Rezurock

— THERAPEUTIC CATEGORIES —
  • Miscellaneous immune disorders

Rezurock Generic Name & Formulations

General Description

Belumosudil 200mg; tabs.

Pharmacological Class

Kinase inhibitor.

How Supplied

Tabs—30

Generic Availability

NO

Mechanism of Action

Belumosudil inhibits rho-associated, coiled-coil containing protein kinase 2 (ROCK2) and ROCK1 with IC50 values of approximately 100 nM and 3 µM, respectively. It downregulates proinflammatory responses via regulation of STAT3/STAT5 phosphorylation and shifting Th17/Treg balance in ex-vivo or in vitro-human T cell assays. Belumosudil also inhibited aberrant pro-fibrotic signaling, in vitro. In vivo, belumosudil demonstrated activity in animal models of chronic GVHD.

Rezurock Indications

Indications

Chronic graft-versus-host disease (GVHD) after failure of ≥2 prior lines of systemic therapy.

Rezurock Dosage and Administration

Adult

Swallow whole. Take with food at the same time each day. 200mg once daily until progression of chronic GVHD that requires new systemic therapy. Concomitant strong CYP3A inducers, PPIs: increase to 200mg twice daily.

Children

<12yrs: not established.

Rezurock Contraindications

Not Applicable

Rezurock Boxed Warnings

Not Applicable

Rezurock Warnings/Precautions

Warnings/Precautions

Monitor LFTs (total bilirubin, AST, ALT) at least monthly. Discontinue permanently if Grade 4 AST/ALT (>20×ULN), Grade ≥3 bilirubin (>3×ULN), or other Grade 4 adverse reactions occur. Withhold if Grade 3 AST/ALT (5–20×ULN), Grade 2 bilirubin (1.5–3×ULN), or other Grade 3 adverse reactions occur until recovery to Grade 0–1; then resume treatment. Pre-existing severe renal impairment: not studied. Moderate or severe hepatic impairment without liver GVHD: avoid. Embryo-fetal toxicity. Advise females of reproductive potential and males (w. female partners) to use effective contraception during and for ≥1 week after the last dose. Pregnancy: exclude status prior to initiation. Nursing mothers: not recommended (during and for ≥1 week after the last dose).

Rezurock Pharmacokinetics

Absorption

Median Tmax at steady state: 1.26–2.53 hours (after a 200 mg once daily or twice daily dose). Mean bioavailability: 64% (after a single dose).

Distribution

Mean volume of distribution: 184 L. Plasma protein bound: 99.9% (albumin).

Metabolism

CYP3A4 (primarily), CYP2C8, CYP2D6, UGT1A9. 

Elimination

Fecal (85%), renal (5%). Half-life: 19 hours. Mean clearance: 9.83 L/hours.

Rezurock Interactions

Interactions

Antagonized by strong CYP3A inducers (eg, rifampin), PPIs (eg, rabeprazole, omeprazole); increase dose (see Adult). Avoid concomitant certain UGT1A1, P-gp, OATP1B1, or BCRP substrates; if unavoidable, reduce dose of substrates.

Rezurock Adverse Reactions

Adverse Reactions

Infections, asthenia, nausea, diarrhea, dyspnea, cough, edema, hemorrhage, abdominal pain, musculoskeletal pain, headache, decreased phosphate, decreased lymphocytes, increased GGT, hypertension; hepatotoxicity.

Rezurock Clinical Trials

See Literature

Rezurock Note

Not Applicable

Rezurock Patient Counseling

See Literature

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