belumosudil (Rx)

Brand and Other Names:Rezurock
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

tablet

  • 200mg

Graft Versus Host Disease

Indicated for chronic graft versus host disease (GVHD) in adults and adolescents aged ≥12 years after failure of at least 2 prior lines of systemic therapy

200 mg PO qDay

Continue until progression of chronic GVHD requires new systemic therapy

Dosage Modifications

Hepatotoxicity

  • Grade 3 AST or ALT (5-20x ULN) or Grade 2 bilirubin (1.5-3x ULN): Hold until recovery of bilirubin, AST, and ALT to Grade 0-1, then resume at recommended dose
  • Grade 4 AST or ALT (>20x ULN) or Grade ≥3 bilirubin (>3x ULN): Permanently discontinue

Other adverse reactions

  • Grade 3: Hold until recovery to Grade 0-1, then resume at recommended dose level
  • Grade 4: Permanently discontinue

Renal impairment

  • Mild-to-moderate (≥30 to <90 mL/min/1.72 m2): No dosage adjustment necessary
  • Severe (<30 mL/min/1.72 m2): Not studied
  • Patients with preexisting severe renal impairment: Not studied; consider risks and potential benefits before initiating treatment

Hepatic impairment

  • Patients with preexisting severe hepatic impairment: Not studied; consider risks and potential benefits before initiating treatment

Strong CYP3A4 inducers

  • If coadministered, increase to 200 mg PO BID

Proton pump inhibitors

  • If coadministered, increase to 200 mg PO BID

Dosing Considerations

Monitoring parameters

  • Monitor total bilirubin, AST, and ALT at least monthly
  • Verify pregnancy status of females of reproductive potential before initiating

Dosage Forms & Strengths

tablet

  • 200mg

Graft Versus Host Disease

Indicated for chronic graft versus host disease (GVHD) in adults and adolescents aged ≥12 years after failure of at least 2 prior lines of systemic therapy

<12 years: Safety and efficacy not established

≥12 years: 200 mg PO qDay

Continue until progression of chronic GVHD requires new systemic therapy

Dosage Modifications

Hepatotoxicity

  • Grade 3 AST or ALT (5-20x ULN) or Grade 2 bilirubin (1.5-3x ULN): Hold until recovery of bilirubin, AST, and ALT to Grade 0-1, then resume at recommended dose
  • Grade 4 AST or ALT (>20x ULN) or Grade ≥3 bilirubin (>3x ULN): Permanently discontinue

Other adverse reactions

  • Grade 3: Hold until recovery to Grade 0-1, then resume at recommended dose level
  • Grade 4: Permanently discontinue

Renal impairment

  • Mild-to-moderate (≥30 to <90 mL/min/1.72 m2): No dosage adjustment necessary
  • Severe (<30 mL/min/1.72 m2): Not studied
  • Patients with pre-existing severe renal impairment: Not studied; consider risks and potential benefits before initiating treatment

Hepatic impairment

  • Patients with pre-existing severe hepatic impairment: Not studied; consider risks and potential benefits before initiating treatment

Strong CYP3A4 inducers

  • If coadministered, increase to 200 mg PO BID

Proton pump inhibitors

  • If coadministered, increase to 200 mg PO BID

Dosing Considerations

Monitoring parameters

  • Monitor total bilirubin, AST, and ALT at least monthly
  • Verify pregnancy status of females of reproductive potential before initiating
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Interactions

Interaction Checker

and belumosudil

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

            All Interactions Sort By:
             activity indicator 

            Contraindicated (0)

              Serious - Use Alternative (1)

              • fexinidazole

                fexinidazole will increase the level or effect of belumosudil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Fexinidazole inhibits CYP3A4. Coadministration may increase risk for adverse effects of CYP3A4 substrates.

              Monitor Closely (1)

              • belzutifan

                belzutifan will decrease the level or effect of belumosudil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If unable to avoid coadministration of belzutifan with sensitive CYP3A4 substrates, consider increasing the sensitive CYP3A4 substrate dose in accordance with its prescribing information.

              Minor (0)

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                Adverse Effects

                >10%

                All grades

                • Infection (unspecified pathogen) (53%)
                • Asthenia (46%)
                • Nausea (42%)
                • Diarrhea (35%)
                • Dyspnea (33%)
                • Cough (30%)
                • Edema (27%)
                • Hemorrhage (23%)
                • Abdominal pain (22%)
                • Musculoskeletal pain (22%)
                • Hypertension (21%)
                • Headache (21%)
                • Viral infection (19%)
                • Pyrexia (18%)
                • Muscle spasm (17%)
                • Decreased appetite (17%)
                • Bacterial infection (16%)
                • Dysphagia (16%)
                • Arthralgia (15%)
                • Nasal congestion (12%)
                • Rash (12%)
                • Pruritus (11%)

                Grade 0-1 (baseline)

                • ALT increased (83%)
                • Creatinine increased (83%)
                • Neutrophil count decreased (83%)
                • Calcium decreased (82%)
                • Potassium increased (82%)
                • Platelets decreased (82%)
                • Alkaline phosphatase increased (80%)
                • Hemoglobin decreased (79%)
                • Phosphate decreased (76%)
                • Lymphocytes decreased (62%)
                • Gamma glutamyl transferase (GGT) increased (47%)

                Grade 2-4 max post

                • Lymphocytes decreased (29%)
                • Phosphate decreased (28%)
                • GGT increased (21%)
                • Calcium decreased (12%)
                • Hemoglobin decreased (11%)

                Grade 3-4

                • Infection (unspecified pathogen) (16%)
                • Max post
                  • Lymphocytes decreased (13%)
                  • GGT increased (11%)

                1-10%

                Grade 2-4 max post

                • Platelets decreased (10%)
                • Alkaline phosphate increased (9%)
                • Neutrophil count decreased (8%)
                • Potassium increased (7%)
                • ALT increased (7%)
                • Creatinine increased (4%)

                Grade 3-4

                • Hypertension (7%)
                • Diarrhea (5%)
                • Dyspnea (5%)
                • Hemorrhage (5%)
                • Viral infection (4%)
                • Bacterial infection (4%)
                • Asthenia (4%)
                • Nausea (4%)
                • Musculoskeletal pain (4%)
                • Arthralgia (2%)
                • Edema (1%)
                • Pyrexia (1%)
                • Abdominal pain (1%)
                • Decreased appetite (1%)
                • Max post
                  • Phosphate decreased (7%)
                  • Platelets decreased (5%)
                  • Neutrophil count decreased (4%)
                  • ALT increased (2%)
                  • Calcium decreased (1%)
                  • Potassium increased (1%)
                  • Hemoglobin decreased (1%)
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                Warnings

                Contraindications

                None

                Cautions

                Can cause fetal harm

                Drug interaction overview

                • Substrate of CYP3A4 and P-gp (in vitro)
                • In vitro studies
                  • Inhibits BCRP, P-gp, and OATP1B1 at clinically relevant concentrations
                  • Inhibits CYP1A2, CYP2C19, CYP2D6, UGT1A1, and UGT1A9
                • Strong CYP3A4 inducers
                  • Increase to 200 mg PO BID
                  • Strong CYP3A inducers decrease exposure and effects of belumosudil
                • Proton pump inhibitors
                  • Increase to 200 mg PO BID
                  • Proton pump inhibitors decrease exposure and effects of belumosudil
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                Pregnancy & Lactation

                Pregnancy

                Based on animal studies and mechanism of action, fetal harm may occur

                No human data are available on use in pregnant females to evaluate for drug-associated risks

                Verify pregnancy status of females of reproductive potential before initiating

                Contraception

                • Females of reproductive potential
                  • Use effective contraception during treatment and for at least 1 week after last dose
                  • If used during pregnancy or if patient becomes pregnant during treatment, inform patient of potential hazard to fetus
                • Males with female partners of reproductive potential
                  • Use effective contraception during treatment and for at least 1 week after last dose

                Infertility

                • Based on animal findings, male or female fertility may be impaired; effects on fertility are reversible

                Animal data

                • Administration of belumosudil to pregnant rats and rabbits during organogenesis resulted in adverse developmental outcomes, including alterations to growth, embryofetal mortality, and embryofetal malformations at maternal exposures approximately ≥3x (rat) and ≥0.07x (rabbit) the human exposure (AUC) at the recommended dose

                Lactation

                There are no data available on drug presence or its metabolites in human milk or effects on breastfed children, or milk production

                Advise lactating females not to breastfeed during treatment and for at least 1 week after last dose

                Pregnancy Categories

                A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

                B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

                C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

                D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

                X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

                NA: Information not available.

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                Pharmacology

                Mechanism of Action

                Inhibitor of rho-associated, coiled-coil–containing protein kinase (ROCK), which inhibits ROCK2 and ROCK1

                Down-regulates proinflammatory responses via regulation of STAT3/STAT5 phosphorylation and shifting Th17/Treg balance in ex vivo or in vitro human T-cell assays

                Also, it inhibits aberrant profibrotic signaling, in vitro

                In vivo, belumosudil demonstrated activity in animal models of chronic GVHD

                Absorption

                Peak plasma concentration: 2,390 ng/mL

                Peak plasma time: 1.26-2.53 hr

                AUC: 22,700 ng⋅hr/mL

                Accumulation ratio: 1.4

                Bioavailability: 64% (single-dose)

                Effect of food

                • Single-dose administration with a high-fat and high-calorie meal (800-1,000 calories with ~50% of total caloric content of the meal from fat): Peak plasma concentration and AUC increased 2.2x and 2x; median peak plasma time was delayed 0.5 hr

                Distribution

                Vd: 184 L

                Protein bound: 99.9% (human serum albumin); 98.6% (human alpha1-acid glycoprotein)

                Metabolism

                Primarily metabolized by CYP3A4 and to a lesser extent by CYP2C8, CYP2D6, and UGT1A9, in vitro

                Elimination

                Half-life: 19 hr

                Clearance: 9.83 L/hr

                Excretion: Feces (85% [30% unchanged]); urine (<5%)

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                Administration

                Oral Administration

                Take with a meal at approximately the same time each day

                Swallow tablets whole; do not cut, crush, or chew

                Missed dose: Do not take extra doses to make up missed dose

                Patients should inform their health care providers of all concomitant medications, including prescription medicines, over-the-counter drugs, vitamins, and herbal products

                Storage

                Store at room temperature, 20-25ºC (68-77ºF); excursions permitted to 15-30ºC (59-86ºF)

                Dispense in original container only

                Store in original container to protect from moisture

                Replace cap securely each time after opening; do not discard desiccant

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                Images

                No images available for this drug.
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                Patient Handout

                A Patient Handout is not currently available for this monograph.
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                Formulary

                FormularyPatient Discounts

                Adding plans allows you to compare formulary status to other drugs in the same class.

                To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

                Adding plans allows you to:

                • View the formulary and any restrictions for each plan.
                • Manage and view all your plans together – even plans in different states.
                • Compare formulary status to other drugs in the same class.
                • Access your plan list on any device – mobile or desktop.

                The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

                Tier Description
                1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
                2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
                3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
                4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
                5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
                6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
                NC NOT COVERED – Drugs that are not covered by the plan.
                Code Definition
                PA Prior Authorization
                Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
                QL Quantity Limits
                Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
                ST Step Therapy
                Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
                OR Other Restrictions
                Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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                Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.