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Belumosudil: Drug information

Belumosudil: Drug information
(For additional information see "Belumosudil: Pediatric drug information" and see "Belumosudil: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Rezurock
Brand Names: Canada
  • Rezurock
Pharmacologic Category
  • ROCK2 Inhibitor
Dosing: Adult
Graft-versus-host disease, chronic

Graft-versus-host disease, chronic: Oral: 200 mg once daily until progression of chronic graft-vs-host disease that requires new systemic therapy or until unacceptable toxicity (Ref).

Missed dose: If a dose is missed, do not administer extra doses to make up the missed dose.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

eGFR ≥30 mL/minute/1.73 m2: There are no dosage adjustments provided in the manufacturer's labeling; however, no clinically meaningful differences in belumosudil pharmacokinetics were observed in mild and moderate renal impairment.

eGFR <30 mL/minute/1.73 m2: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); consider risks versus potential benefits of initiating belumosudil in patients with severe renal impairment.

Dosing: Hepatic Impairment: Adult

Hepatic impairment at treatment initiation:

Mild impairment (Child-Turcotte-Pugh class A): No dosage adjustment necessary.

Moderate to severe impairment (Child-Turcotte-Pugh class B or C) without liver graft-versus-host disease: Avoid use.

Hepatotoxicity during treatment:

Grade 3 AST or ALT elevation (5 to 20 times ULN) or grade 2 bilirubin elevation (1.5 to 3 times ULN): Hold belumosudil until recovery of bilirubin, AST and ALT to grade 0 or 1, then resume belumosudil at the recommended dose.

Grade 4 AST or ALT elevation (>20 times ULN) or ≥ grade 3 bilirubin elevation (>3 times ULN): Permanently discontinue belumosudil.

Dosing: Adjustment for Toxicity: Adult

Grade 3 adverse reaction: Hold belumosudil until recovery to grade 0 or 1, then resume belumosudil at the recommended dose level.

Grade 4 adverse reaction: Permanently discontinue belumosudil.

Dosing: Older Adult

Refer to adult dosing.

Dosing: Pediatric

(For additional information see "Belumosudil: Pediatric drug information")

Graft-versus-host disease, chronic, treatment

Graft-versus-host disease (GVHD), chronic, treatment: Children ≥12 years and Adolescents: Oral: 200 mg once daily until progression of chronic GVHD that requires new systemic therapy or until unacceptable toxicity (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosage adjustment for toxicity:

Grade 3 adverse reactions: Withhold belumosudil until recovery to grade 0 to 1, then resume belumosudil at recommended dose.

Grade 4 adverse reactions: Permanently discontinue belumosudil.

Dosing: Kidney Impairment: Pediatric

Children ≥12 years and Adolescents:

GFR ≥30 mL/minute/1.73 m2: There are no dosage adjustments provided in the manufacturer's labeling; however, no clinically meaningful differences in belumosudil pharmacokinetics were observed in mild and moderate kidney impairment.

GFR <30 mL/minute/1.73 m2: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied). Consider the risks versus the potential benefits of belumosudil prior to initiating therapy in patients with severe kidney impairment.

Dosing: Hepatic Impairment: Pediatric

Children ≥12 years and Adolescents:

Baseline hepatic impairment: There are no dosage adjustments provided in the manufacturer's labeling. Consider the risks versus the potential benefits of initiating belumosudil in patients with severe hepatic impairment.

Hepatotoxicity during treatment:

Grade 3 AST or ALT (5 to 20 times ULN) or grade 2 bilirubin (1.5 to 3 times ULN): Withhold belumosudil until recovery of AST, ALT, and bilirubin to grade 0 to 1, then resume belumosudil at recommended dose.

Grade 4 AST or ALT (>20 times ULN) or ≥ grade3 bilirubin (>3 times ULN): Permanently discontinue belumosudil.

Adverse Reactions (Significant): Considerations
Infection

Infection, including serious infection, has been reported with belumosudil; however, trials involve patients with chronic graft-vs-host disease currently receiving or who previously received known immunosuppressant agents (standard of care) which are associated with an increased risk of infection, thereby making it difficult to ascertain the risk of infection associated with belumosudil (Ref).

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%:

Cardiovascular: Edema (27%), hypertension (21%)

Dermatologic: Pruritus (11%), skin rash (12%)

Endocrine & metabolic: Decreased serum calcium (12%), decreased serum phosphate (28%), increased gamma-glutamyl transferase (21%)

Gastrointestinal: Abdominal pain (22%), decreased appetite (17%), diarrhea (35%), dysphagia (16%), nausea (42%)

Hematologic & oncologic: Decreased hemoglobin (11%; grades 3/4: 1%), hemorrhage (23%; grade 3/4: 5%), lymphocytopenia (29%; grades 3/4: 13%)

Infection: Bacterial infection (16%), infection (53%), viral infection (19%)

Nervous system: Headache (21%)

Neuromuscular & skeletal: Arthralgia (15%), asthenia (46%), muscle spasm (17%), musculoskeletal pain (22%)

Respiratory: Cough (30%), dyspnea (33%), nasal congestion (12%)

Miscellaneous: Fever (18%)

1% to 10%:

Endocrine & metabolic: Increased serum potassium (7%)

Hematologic & oncologic: Decreased neutrophils (8%; grades 3/4: 4%), decreased platelet count (10%; grade 3/4: 5%)

Hepatic: Increased serum alanine aminotransferase (7%), increased serum alkaline phosphatase (9%)

Renal: Increased serum creatinine (4%)

Contraindications

There are no contraindications listed in the manufacturer's labeling.

Canadian labeling: Hypersensitivity to belumosudil or any component of the formulation.

Warnings/Precautions

There are no warnings listed in the manufacturer's labeling.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Rezurock: 200 mg

Generic Equivalent Available: US

No

Pricing: US

Tablets (Rezurock Oral)

200 mg (per each): $714.99

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Rezurock: 200 mg

Prescribing and Access Restrictions

Belumosudil is available through authorized specialty pharmacies and specialty distributors. Information is available at https://rezurockhcp.com/obtaining-rezurock/.

Administration: Adult

Oral: Administer with a meal at approximately the same time each day. Swallow whole; do not cut, crush, or chew tablets.

Administration: Pediatric

Oral: Swallow tablets whole with a glass of water; do not cut, crush, or chew tablets. Administer with a meal at approximately the same time daily.

Hazardous Drugs Handling Considerations

This medication is not on the NIOSH (2016) list; however, it may meet the criteria for a hazardous drug. Belumosudil may cause teratogenicity and reproductive toxicity.

Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).

Note: Facilities may perform risk assessment of some hazardous drugs to determine if appropriate for alternative handling and containment strategies (USP-NF 2020). Refer to institution-specific handling policies/procedures.

Use: Labeled Indications

Graft-vs-host disease, chronic: Treatment of chronic graft-vs-host disease in adult and pediatric patients ≥12 years of age after failure of at least 2 prior lines of systemic therapy.

Medication Safety Issues
Sound-alike/look-alike issues:

Belumosudil may be confused with belimumab, belinostat, budesonide.

Metabolism/Transport Effects

Substrate of CYP2C8 (minor), CYP2D6 (minor), CYP3A4 (major), P-glycoprotein/ABCB1 (minor), UGT1A9; Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Antacids: May decrease the serum concentration of Belumosudil. Management: Consider separating administration of belumosudil and antacids by 2 hours and monitor for reduced belumosudil efficacy. Risk D: Consider therapy modification

CYP3A4 Inducers (Moderate): May decrease the serum concentration of Belumosudil. Risk C: Monitor therapy

CYP3A4 Inducers (Strong): May decrease the serum concentration of Belumosudil. Management: Increase the dose of belumosudil to 200 mg twice daily when coadministered with strong CYP3A4 inducers. Risk D: Consider therapy modification

Histamine H2 Receptor Antagonists: May decrease the serum concentration of Belumosudil. Risk C: Monitor therapy

Inhibitors of the Proton Pump (PPIs and PCABs): May decrease the serum concentration of Belumosudil. Management: Increase the dose of belumosudil to 200 mg twice daily when coadministered with inhibitors of the proton pump (PPIs and PCABs). Risk D: Consider therapy modification

Food Interactions

Belumosudil Cmax and AUC increased 2.2 times and 2 times, respectively, following administration of a single belumosudil dose with a high-fat and high-calorie meal (800 to 1,000 calories with ~50% of calories from fat) compared to the fasted state (in healthy subjects). Management: Administer with a meal.

Reproductive Considerations

Verify pregnancy status prior to use in patients who may become pregnant.

Patients who may become pregnant and patients with partners who may become pregnant should use effective contraception during therapy and for 1 week after the last belumosudil dose.

Based on data from animal studies, belumosudil may reversibly impair fertility.

Pregnancy Considerations

Based on the mechanism of action and data from animal reproduction studies, in utero exposure to belumosudil may cause fetal harm.

Breastfeeding Considerations

It is not known if belumosudil is present in breast milk.

Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer during therapy and for 1 week after the last belumosudil dose.

Monitoring Parameters

Monitor total bilirubin, AST, and ALT at least monthly. Verify pregnancy status prior to use in patients who may become pregnant. Monitor adherence.

Mechanism of Action

Belumosudil is a kinase inhibitor which selectively inhibits rho-associated, coiled-coil containing protein kinase (ROCK), predominantly inhibiting ROCK2 and to a lesser extent, ROCK1. ROCK2 inhibition downregulates signal transducer and activator of transcription 3 (STAT3) phosphorylation and decreases expression of type 17 helper T-cell (Th17) transcription factors (Cutler 2021). ROCK2 inhibition also restores immune system balance via upregulation of signal transducer and activator of transcription 5 (STAT5), which results in shifting Th17/regulatory T-cell balance (Jagasia 2021). Belumosudil inhibition of ROCK2 results in downregulation of proinflammatory responses and inhibits aberrant profibrotic signaling.

Pharmacokinetics (Adult Data Unless Noted)

Distribution: Vd: 184 L.

Protein binding: 99.9% (to human serum albumin); 98.6% to human alpha 1-acid glycoprotein.

Metabolism: Primarily by CYP3A4 and to a lesser extent by CYP2C8, CYP2D6, and UGT1A9.

Bioavailability: 64%.

Half-life elimination: 19 hours.

Time to peak: ~1.3 to 2.5 hours (delayed ~0.5 hours with a high-fat/high-calorie meal).

Excretion: Feces: 85% (30% as unchanged drug); urine: <5%.

Clearance: 9.83 L/hour.

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

Hepatic function impairment: Total concentrations of AUC increased 1.4-fold, 1.5-fold, and 4.2-fold, respectively, in patients with mild, moderate, or severe impairment compared to patients with normal hepatic function. AUC of free concentrations decreased 19%, increased 1.4-fold, and increased 16-fold, respectively, in patients with mild, moderate, or severe impairment compared to patients with normal hepatic function.

  1. <800> Hazardous Drugs–Handling in Healthcare Settings. United States Pharmacopeia and National Formulary (USP 43-NF 38). Rockville, MD: United States Pharmacopeia Convention; 2020:74-92.
  2. Cutler CS, Lee SJ, Arai S, et al. Belumosudil for chronic graft-versus-host disease (cGVHD) after 2 or more prior lines of therapy: the ROCKstar study. Blood. Published online July 15, 2021. doi:10.1182/blood.2021012021 [PubMed 34265047]
  3. Jagasia M, Lazaryan A, Bachier CR, et al. ROCK2 inhibition with belumosudil (KD025) for the treatment of chronic graft-versus-host disease. J Clin Oncol. 2021;39(17):1888-1898. doi:10.1200/JCO.20.02754 [PubMed 33877856]
  4. Przepiorka D, Le RQ, Ionan A, et al. FDA Approval Summary: Belumosudil for adult and pediatric patients 12 years and older with chronic GVHD after two or more prior lines of systemic therapy. Clin Cancer Res. Published online February 8, 2022. doi:10.1158/1078-0432.CCR-21-4176 [PubMed 35135839]
  5. Rezurock (belumosudil) [prescribing information]. Bridgewater, NJ: Kadmon Pharmaceuticals LLC; November 2023.
  6. Rezurock (belumosudil) [product monograph]. Laval, Quebec, Canada: Sanofi-Aventis Canada; October 2022.
  7. US Department of Health and Human Services; Centers for Disease Control and Prevention; National Institute for Occupational Safety and Health. NIOSH list of antineoplastic and other hazardous drugs in healthcare settings 2016. https://www.cdc.gov/niosh/docs/2016-161/default.html. Updated September 2016. Accessed July 26, 2021.
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