Overview
11 DESCRIPTION Belumosudil is a kinase inhibitor. The active pharmaceutical ingredient is belumosudil mesylate with the molecular formula C 27 H 28 N 6 O 5 S and the molecular weight is 548.62 g/mol. The chemical name for belumosudil mesylate is 2-{3-[4-(1 H -indazol-5-ylamino)-2-quinazolinyl]phenoxy}- N -(propan-2-yl) acetamide methanesulfonate (1:1).
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Belumosudil is an inhibitor of rho-associated, coiled-coil containing protein kinase (ROCK) which inhibits ROCK2 and ROCK1 with IC 50 values of approximately 100 nM and 3 µM, respectively. Belumosudil down-regulated 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. 12.2 Pharmacodynamics Belumosudil exposure-response relationships and the time course of pharmacodynamic response are not established. Cardiac Electrophysiology At 2.
Indications
- 1 INDICATIONS AND USAGE REZUROCK is indicated for the treatment of adult and pediatric patients 12 years and older with chronic graft-versus-host disease (chronic GVHD) after failure of at least two prior lines of systemic therapy. REZUROCK is a kinase inhibitor indicated for the treatment of adult and pediatric patients 12 years and older with chronic graft-versus-host disease (chronic GVHD) after failure of at least two prior lines of systemic therapy. ( 1 )
Common Doses
- 200 mg
Dosage
2 DOSAGE AND ADMINISTRATION Recommended Dosage : 200 mg taken orally once daily with food. ( 2.1 ) 2.1 Recommended Dosage The recommended dose of REZUROCK is 200 mg given orally once daily until progression of chronic GVHD that requires new systemic therapy. Instruct the patient on the following: Swallow REZUROCK tablets whole. Do not cut, crush, or chew tablets. Take REZUROCK with a meal at approximately the same time each day [see Clinical Pharmacology (12.3) ] . If a dose of REZUROCK is missed, instruct the patient to not take extra doses to make up the missed dose.
Contraindications
- 4 CONTRAINDICATIONS None. None. ( 4 )
Side Effects
- 6 ADVERSE REACTIONS The most common (≥20%) adverse reactions, including laboratory abnormalities, are infections, asthenia, nausea, diarrhea, dyspnea, cough, edema, hemorrhage, abdominal pain, musculoskeletal pain, headache, phosphate decreased, gamma glutamyl transferase increased, lymphocytes decreased, and hypertension. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Kadmon Pharmaceuticals, LLC at 1-800-633-1610 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.
Interactions
- 7 DRUG INTERACTIONS Strong CYP3A Inducers : Increase REZUROCK dosage to 200 mg twice daily. ( 7.1 , 2.3 ) Proton Pump Inhibitors : Increase REZUROCK dosage to 200 mg twice daily. ( 7.1 , 2.3 ) BCRP Substrates: Avoid concomitant use with drugs that are BCRP substrates where possible. If used together, monitor patients more frequently for adverse reactions and decrease the substrates dosage(s) in accordance with the respective Prescribing Information. ( 7.