Rezurock belumosudil 200 mg Tablet, 30-count
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Selective immunosuppressants class.
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🏭 Manufacturer & labeler
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🩺 Clinical
Belumosudil is used to treat graft versus host disease (GVHD; a complication of hematopoietic stem-cell transplant [HSCT; a procedure that replaces diseased bone marrow with healthy bone marrow]) in adults and children 12 years of age and older who were treated unsuccessfully with at least two other treatments. Belumosudil is in a class of medications called kinase inhibitors. It works to treat GVHD by blocking the signals of the cells that cause GVHD.
Read the full MedlinePlus article ↗- Chronic GVHD (graft-versus-host disease) happens after a stem cell or bone marrow transplant, when the donor's immune cells treat your body as foreign and attack it. It can cause i...
- What exactly is chronic GVHD, and why do I need this specific medication?
- Yes, it really matters. Taking Rezurock with a meal roughly doubles the amount your body absorbs compared to taking it on an empty stomach. Always take it with food — and try to ta...
- Does it matter if I take Rezurock with food or on an empty stomach?
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Some supplements/herbs that may interact with Belumosudil Mesylate — tap one for details:
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
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Croscarmellose sodium is a plant-based substance derived from cellulose. It acts as a disintegrant, helping tablets and capsules break down quickly in the digestive system so the medicine can be absorbed.
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Ferric oxide yellow is a naturally occurring iron compound used as a colorant in medications. It gives tablets, capsules, and other forms a yellow or golden hue for identification and appearance.
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Hypromellose is a plant-based thickener made from cellulose. It's used in medicines as a binder to hold ingredients together, a coating for tablets, and a thickener for liquids.
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Magnesium stearate is a salt made from magnesium and stearic acid, a fatty substance. It's used in tablets and capsules as a lubricant and glidant to help ingredients flow smoothly during manufacturing and prevent sticking.
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Microcrystalline cellulose is a purified form of cellulose, a natural fiber from plant sources. It acts as a binder and filler in tablets and capsules, helping hold ingredients together and give the medicine its shape and size.
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Polyethylene glycol is a synthetic liquid or solid polymer used in medicines as a solvent, lubricant, and humectant. It helps dissolve active ingredients, reduces friction during manufacturing, and retains moisture in the final product.
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A powder made from a naturally occurring mineral. In medicines, talc works as a glidant and anti-caking agent, helping tablets and capsules flow smoothly during manufacturing and preventing clumping.
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Titanium dioxide is a bright white mineral powder commonly used as a colorant and opacifying agent. It makes pills and tablets white or lighter in color and helps make coatings non-transparent.
10 inactive ingredients listed in the exact product block matched to this NDC.
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ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per each | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | $604.51 | $18,135.36 / 30 tablets |
| Medicare drug plans payPart D · Q2 2026 | $630.27 | $18,908.19 / 30 tablets |
| Medicare Part B allowsASP · J7599 | No ASP payment limit on file for J7599 this quarter. | |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Rezurock 200 mgthis 79802-0200-30 | Kadmon | 30 tablets | — | — | FDA listed | — |
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⏳ Availability & generic status
We did not find an FDA-approved generic match for this exact strength, form and route. Patent/protection dates below may affect future generic timing.
Why the date isn’t exact: Generic timing can change because patents may be challenged, settled, licensed, added, removed, or worked around with a narrower label — and FDA approval does not always mean a pharmacy can get the generic today.
🛈 What do these terms mean?
- Patent
- Legal protection listed in the Orange Book that may delay generic approval or launch. Issued by the U.S. Patent & Trademark Office.
- Substance patent
- Covers the active drug molecule itself — the hardest to design around. A generic generally can’t launch until it expires.
- Formulation (product) patent
- Covers a specific formulation or dosage form. A generic can sometimes work around it with a different formulation.
- Method-of-use patent
- A patent covering one specific approved use of the drug — not necessarily the whole molecule. A generic can sometimes launch with a “skinny label” that carves out the protected use and keeps the others.
- Skinny label
- A generic label that omits a still-patented use when the FDA allows it — letting a generic reach the market for the unprotected uses.
- Exclusivity
- FDA-granted marketing protection, separate from patents — e.g. 5-yr new chemical entity, 7-yr orphan drug, or a +6-month pediatric extension.
- Paragraph IV
- A generic applicant’s formal challenge to a listed patent. It can potentially lead to earlier generic entry, but often involves litigation or a settlement.
- RLD / RS
- Reference Listed Drug — the brand product the FDA uses as the reference for generic applications. Reference Standard — the product the FDA expects generics to compare against in bioequivalence testing.
- TE / AB rating
- FDA therapeutic-equivalence rating. An AB rating generally means the FDA considers a generic therapeutically equivalent to — and substitutable for — the brand.
- LOE (loss of exclusivity)
- The latest patent or exclusivity currently listed — the loss-of-exclusivity / latest-listed-protection date shown on this page. Paragraph-IV challenges and settlements can move the real date earlier; FDA approval and a manufacturer’s decision to market can move it later.
Built from the FDA Orange Book. The bars above are scaled to each protection’s expiry; the red LOE marker is the last one to lapse.
| Patent | Type | Use code | Expires |
|---|---|---|---|
| US 10183931 ↗ | Method of use | U-4260 | Oct 7, 2033 |
| US 10696660 ↗ | Method of use | U-4260 | Oct 7, 2033 |
| US 8357693 ↗ | Drug substance | U-4259 | Jun 20, 2034 |
| US 12097202 ↗ | Method of use | U-4014 | Jul 14, 2042 |
| US 11311541 ↗ | Method of use | U-3369 | Apr 9, 2035 |
| US 10696660 ↗ | Method of use | U-3246 | Oct 7, 2033 |
| US 10183931 ↗ | Method of use | U-3246 | Oct 7, 2033 |
| Code | What it grants | Expires |
|---|---|---|
| NCE | New Chemical Entity (5-year) | Jul 16, 2026 |
| ODE-362 | Orphan Drug Exclusivity (7-year) | Jul 16, 2028 |
Is there a generic version of REZUROCK 200 MG TABLET?
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🗺️ Medicaid utilization & spend
📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
🔬 Reported adverse events (FAERS)
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 79802-0200-30 You're viewing this | 1 BOTTLE in 1 CARTON (79802-200-30) / 30 TABLET in 1 BOTTLE | 2021-07-16 | Active |
🧭 About this NDC listing & data coverage
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| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | ✓ Available |
| Inactive ingredients (structured) | ✓ Available |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | ✓ Available |
| Medicaid utilization (CMS SDUD) | ✓ Available |
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📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
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 )
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION Recommended Dosage : 200 mg taken orally once daily with food. ( 2.1 )
2.1Recommended 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. Treatment with REZUROCK has not been studied in patients with pre-existing severe renal impairment.
For patients with pre-existing severe renal impairment, consider the risks and potential benefits before initiating treatment with REZUROCK [see Clinical Pharmacology (12.3) ] .
2.2Dosage Modifications for Adverse Reactions Monitor total bilirubin, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) at least monthly. Modify the REZUROCK dosage for adverse reactions as per Table 1. Table 1: Recommended Dosage Modifications for REZUROCK for Adverse Reactions Adverse Reaction Severity Based on CTCAE v
4.03REZUROCK Dosage Modifications Hepatotoxicity [see Adverse Reactions (6.1) ] Grade 3 AST or ALT (5× to 20× ULN) or Grade 2 bilirubin (1.5× to 3× ULN) Hold REZUROCK until recovery of bilirubin, AST and ALT to Grade 0–1, then resume REZUROCK at the recommended dose. Grade 4 AST or ALT (more than 20× ULN) or Grade ≥3 bilirubin (more than 3× ULN) Discontinue REZUROCK permanently. Other adverse reactions [see Adverse Reactions (6.1) ] Grade 3 Hold REZUROCK until recovery to Grade 0–1, then resume REZUROCK at the recommended dose level.
Grade 4 Discontinue REZUROCK permanently.
2.3Dosage Modification Due to Drug Interactions Strong CYP3A Inducers Increase the dosage of REZUROCK to 200 mg twice daily when coadministered with strong CYP3A inducers [see Drug Interactions (7.1) ] . Proton Pump Inhibitors Increase the dosage of REZUROCK to 200 mg twice daily when coadministered with proton pump inhibitors [see Drug Interactions (7.1) ] .
2.4Recommended Dosage in Patients with Hepatic Impairment Avoid use in patients with moderate hepatic impairment (Child-Pugh B) or severe hepatic impairment (Child-Pugh C) without liver GVHD [see Use in Specific Populations (8.7) , Clinical Pharmacology (12.3) ] . No dosage adjustment is recommended when administering REZUROCK to patients with mild hepatic impairment [see Use in Specific Populations (8.7) , Clinical Pharmacology (12.3) ] .
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Each 200 mg belumosudil tablet is a pale yellow film-coated oblong tablet debossed with "KDM" on one side and "200" on the other side. Tablet: 200 mg. ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS None. None. ( 4 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Embryo-Fetal Toxicity : Can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception. ( 5.1 , 8.1 , 8.3 )
5.1Embryo-Fetal Toxicity Based on findings in animals and its mechanism of action, REZUROCK can cause fetal harm when administered to a pregnant woman. In animal reproduction studies, administration of belumosudil to pregnant rats and rabbits during the period of organogenesis caused adverse developmental outcomes including embryo-fetal mortality and malformations at maternal exposures (AUC) less than those in patients at the recommended dose. Advise pregnant women of the potential risk to a fetus.
Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment with REZUROCK and for one week after the last dose [see Use in Specific Populations (8.1 , 8.3) , Nonclinical Toxicology (13.1) ] .
🤒 Adverse Reactions ▾
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.
6.1Clinical Trial Experience Because clinical trials are conducted under widely variable conditions, adverse reaction rates observed in clinical trials of a drug cannot be directly compared with rates of clinical trials of another drug and may not reflect the rates observed in practice. Chronic Graft versus Host Disease In two clinical trials (Study KD025-213 and Study KD025-208), 83 adult patients with chronic GVHD were treated with REZUROCK 200 mg once daily [see Clinical Studies (14.1) ] . The median duration of treatment was 9.2 months (range 0.5 to 44.7 months).
Fatal adverse reaction was reported in one patient with severe nausea, vomiting, diarrhea and multi-organ failure. Permanent discontinuation of REZUROCK due to adverse reactions occurred in 18% of patients. The adverse reactions which resulted in permanent discontinuation of REZUROCK in >3% of patients included nausea (4%).
Adverse reactions leading to dose interruption occurred in 29% of patients. The adverse reactions leading to dose interruption in ≥2% were infections (11%), diarrhea (4%), and asthenia, dyspnea, hemorrhage, hypotension, liver function test abnormal, nausea, pyrexia, edema, and renal failure with (2% each). The most common (≥20%) adverse reactions, including laboratory abnormalities, were infections, asthenia, nausea, diarrhea, dyspnea, cough, edema, hemorrhage, abdominal pain, musculoskeletal pain, headache, phosphate decreased, gamma glutamyl transferase increased, lymphocytes decreased, and hypertension.
Table 2 summarizes the nonlaboratory adverse reactions. Table 2: Nonlaboratory Adverse Reactions in ≥10% Patients with Chronic GVHD Treated with REZUROCK Adverse Reaction REZUROCK 200 mg once daily (N=83) All Grades (%) Grades 3–4 (%) Infections and infestations Infection (pathogen not specified) infection with an unspecified pathogen includes acute sinusitis, device related infection, ear infection, folliculitis, gastroenteritis, gastrointestinal infection, hordeolum, infectious colitis, lung infection, skin infection, tooth infection, urinary tract infection, wound infection, upper respiratory tract infection, pneumonia, conjunctivitis, sinusitis, respiratory tract infection, bronchitis, sepsis, septic shock.
53 16 Viral infection includes influenza, rhinovirus infection, gastroenteritis viral, viral upper respiratory tract infection, bronchitis viral, Epstein-Barr viremia, Epstein-Barr virus infection, parainfluenzae virus infection, Varicella zoster virus infection, viral infection. 19 4 Bacterial infection includes cellulitis, Helicobacter infection, Staphylococcal bacteremia, catheter site cellulitis, Clostridium difficile colitis, Escherichia urinary tract infection, gastroenteritis Escherichia coli, Pseudomonas infection, urinary tract infection bacterial.
16 4 General disorders and administration site conditions Asthenia includes fatigue, asthenia, malaise. 46 4 Edema includes edema peripheral, generalized edema, face edema, localized edema, edema. 27 1 Pyrexia 18 1 Gastrointestinal Nausea includes nausea, vomiting.
42 4 Diarrhea 35 5 Abdominal pain includes abdominal pain, abdominal pain upper, abdominal pain lower. 22 1 Dysphagia 16 0 Respiratory, thoracic and mediastinal Dyspnea includes dyspnea, dyspnea exertional, apnea, orthopnea, sleep apnea syndrome. 33 5 Cough includes cough, productive cough.
30 0 Nasal congestion 12 0 Vascular Hemorrhage includes contusion, hematoma, epistaxis, increased tendency to bruise, conjunctival hemorrhage, hematochezia, mouth hem…
🔄 Drug 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. ( 7.2 ) OATP1B1 Substrates: If used together, monitor patients more frequently for adverse reactions and decrease the substrates dosage(s) in accordance with the respective Prescribing Information. ( 7.2 ) Certain CYP1A2, CYP3A, P-gp or UGT1A1 Substrates : Avoid concomitant use with these substrates for which minimal concentration changes may lead to serious toxicities.
If concomitant use cannot be avoided, decrease the substrates dosage(s) in accordance with the respective Prescribing Information. ( 7.2 )
7.1Effect of Other Drugs on REZUROCK Proton Pump Inhibitors Belumosudil exhibits pH-dependent solubility. Concomitant use of REZUROCK with proton pump inhibitors decreases belumosudil exposure [see Clinical Pharmacology (12.3) ] , which may reduce the efficacy of REZUROCK. Increase the dosage of REZUROCK when used concomitantly with proton pump inhibitors [see Dosage and Administration (2.3) ].
Strong CYP3A Inducers Belumosudil is a CYP3A substrate. Concomitant use of REZUROCK with strong CYP3A inducers decreases belumosudil exposure [see Clinical Pharmacology (12.3) ] , which may reduce the efficacy of REZUROCK. Increase the dosage of REZUROCK when used concomitantly with strong CYP3A inducers [see Dosage and Administration (2.3) ].
7.2Effect of REZUROCK on Other Drugs BCRP and OATP1B1 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 BCRP substrates dosage(s) in accordance with the respective Prescribing Information. Belumosudil is a BCRP inhibitor.
Concomitant use of REZUROCK with BCRP substrates increases their plasma concentrations [see Clinical Pharmacology (12.3) ] , which may increase the risk of adverse reactions related to these substrates. Belumosudil is an OATP1B1 inhibitor. Concomitant use of REZUROCK with OATP1B1 substrates may increase their plasma concentrations.
Monitor patients more frequently for adverse reactions of these substrates and decrease the OATP1B1 substrates dosage(s) in accordance with the respective Prescribing Information [see Clinical Pharmacology (12.3) ] . Certain CYP1A2 Substrates Avoid concomitant use of REZUROCK with drugs that are sensitive CYP1A2 substrates, for which minimal concentration changes may lead to serious toxicities. If concomitant use cannot be avoided, decrease the CYP1A2 substrate dosage(s) in accordance with the respective Prescribing Information.
Belumosudil is a CYP1A2 inhibitor. Concomitant use of REZUROCK with sensitive CYP1A2 substrates (e.g., caffeine) is predicted to increase CYP1A2 substrate exposure [see Clinical Pharmacology (12.3) ] , which may increase the risk of adverse reactions related to these substrates. Certain CYP3A Substrates Avoid concomitant use of REZUROCK with drugs that are sensitive CYP3A substrates, for which minimal concentration changes may lead to serious toxicities.
If concomitant use cannot be avoided, decrease the CYP3A substrate dosage(s) in accordance with the respective Prescribing Information. Belumosudil is a CYP3A inhibitor. Concomitant use of REZUROCK with sensitive CYP3A substrates (e.g., midazolam) is predicted to increase CYP3A substrate exposure [see Clinical Pharmacology (12.3) ] , which may increase the risk of adverse reactions related to these substrates.
Certain UGT1A1 Substrates Avoid concomitant use of REZUROCK with drugs that are UGT1A1 substrates, for which minimal concentration changes may lead to serious toxicities. If concomitant use cannot be…
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS Lactation : Advise not to breastfeed. ( 8.2 ) Moderate or Severe Hepatic Impairment: Avoid use of REZUROCK in patients with moderate or severe hepatic impairment. ( 2.4 , 8.7 )
8.1Pregnancy Risk Summary Based on findings from animal studies and the mechanism of action [see Clinical Pharmacology (12.1) ] , REZUROCK can cause fetal harm when administered to pregnant women. There are no available human data on REZUROCK use in pregnant women to evaluate for a drug-associated risk. In animal reproduction studies, administration of belumosudil to pregnant rats and rabbits during the period of organogenesis resulted in adverse developmental outcomes, including alterations to growth, embryo-fetal mortality, and embryo-fetal malformations at maternal exposures (AUC) approximately ≥1.4 (rat) and ≥0.08 (rabbit) times the human exposure (AUC) at the recommended dose (see Data ) .
Advise pregnant women and females of reproductive potential of the potential risk to the fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal data Embryo-fetal development studies were conducted in rats with administration of belumosudil to pregnant animals during the period of organogenesis at oral doses of 25, 50, 150, and 300 mg/kg/day in a pilot study and doses of 15, 50, and 150 mg/kg/day in a pivotal study.
In the pilot study, maternal toxicity and embryo-fetal developmental effects were observed. Maternal toxicity (reduced body weight gain) occurred at 150 and 300 mg/kg/day doses. Increased post-implantation loss occurred at 50 and 300 mg/kg/day.
Fetal-malformations were observed at ≥50 mg/kg/day and included absence of anus and tail, omphalocele, and dome shaped head. The exposure (AUC) at 50 mg/kg/day in rats is approximately 1.4 times the human exposure at the recommended dose of 200 mg. In an embryo-fetal developmental study in rabbits, pregnant animals administered oral doses of belumosudil at 50, 125, and 225 mg/kg/day during the period of organogenesis resulted in maternal toxicity and embryo-fetal developmental effects.
Maternal toxicity (body weight loss and mortality) was observed at doses ≥125 mg/kg/day. Embryo-fetal effects were observed at doses ≥50 mg/kg/day and included spontaneous abortion, increased post-implantation loss, decreased percentage of live fetuses, malformations, and decreased fetal body weight. Malformations included those in the tail (short), ribs (branched, fused or deformed), sternebrae (fused), and neural arches (fused, misaligned, and deformed).
The exposure (AUC) at 50 mg/kg/day in rabbits is approximately 0.08 times the human exposure at the recommended dose of 200 mg.
8.2Lactation Risk Summary There are no data available on the presence of belumosudil or its metabolites in human milk or the effects on the breastfed child, or milk production. Because of the potential for serious adverse reactions from belumosudil in the breastfed child, advise lactating women not to breastfeed during treatment with REZUROCK and for one week after the last dose.
8.3Females and Males of Reproductive Potential REZUROCK can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1) ] . Pregnancy Testing Verify the pregnancy status of females of reproductive potential prior to initiating treatment with REZUROCK. Contraception Females Advise females of reproductive potential to use effective contraception during treatment with REZUROCK and for one week after the last dose of REZUROCK.
If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be informed of the potential hazard to a fetus. Males Advise males with female partners of reproductive potential to use effective contraception during treatment with REZUROCK and for one week after the last dose of REZUROCK. Infertility Fe…
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary Based on findings from animal studies and the mechanism of action [see Clinical Pharmacology (12.1) ] , REZUROCK can cause fetal harm when administered to pregnant women. There are no available human data on REZUROCK use in pregnant women to evaluate for a drug-associated risk. In animal reproduction studies, administration of belumosudil to pregnant rats and rabbits during the period of organogenesis resulted in adverse developmental outcomes, including alterations to growth, embryo-fetal mortality, and embryo-fetal malformations at maternal exposures (AUC) approximately ≥1.4 (rat) and ≥0.08 (rabbit) times the human exposure (AUC) at the recommended dose (see Data ) .
Advise pregnant women and females of reproductive potential of the potential risk to the fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal data Embryo-fetal development studies were conducted in rats with administration of belumosudil to pregnant animals during the period of organogenesis at oral doses of 25, 50, 150, and 300 mg/kg/day in a pilot study and doses of 15, 50, and 150 mg/kg/day in a pivotal study.
In the pilot study, maternal toxicity and embryo-fetal developmental effects were observed. Maternal toxicity (reduced body weight gain) occurred at 150 and 300 mg/kg/day doses. Increased post-implantation loss occurred at 50 and 300 mg/kg/day.
Fetal-malformations were observed at ≥50 mg/kg/day and included absence of anus and tail, omphalocele, and dome shaped head. The exposure (AUC) at 50 mg/kg/day in rats is approximately 1.4 times the human exposure at the recommended dose of 200 mg. In an embryo-fetal developmental study in rabbits, pregnant animals administered oral doses of belumosudil at 50, 125, and 225 mg/kg/day during the period of organogenesis resulted in maternal toxicity and embryo-fetal developmental effects.
Maternal toxicity (body weight loss and mortality) was observed at doses ≥125 mg/kg/day. Embryo-fetal effects were observed at doses ≥50 mg/kg/day and included spontaneous abortion, increased post-implantation loss, decreased percentage of live fetuses, malformations, and decreased fetal body weight. Malformations included those in the tail (short), ribs (branched, fused or deformed), sternebrae (fused), and neural arches (fused, misaligned, and deformed).
The exposure (AUC) at 50 mg/kg/day in rabbits is approximately 0.08 times the human exposure at the recommended dose of 200 mg.
🧒 Pediatric Use ▾
8.4Pediatric Use The safety and effectiveness of REZUROCK have been established in pediatric patients 12 years and older. Use of REZUROCK in this age group is supported by evidence from adequate and well-controlled studies of REZUROCK in adults with additional population pharmacokinetic data demonstrating that age and body weight had no clinically meaningful effect on the pharmacokinetics of drug substance, that the exposure of drug substance is expected to be similar between adults and pediatric patients age 12 years and older, and that the course of disease is sufficiently similar in adult and pediatric patients to allow extrapolation of data in adults to pediatric patients.
The safety and effectiveness of REZUROCK in pediatric patients less than 12 years old have not been established.
🧓 Geriatric Use ▾
8.5Geriatric Use Of the 186 patients with chronic GVHD in clinical studies of REZUROCK, 26% were 65 years and older. No clinically meaningful differences in safety or effectiveness of REZUROCK were observed in comparison to younger patients.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism 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.
12.2Pharmacodynamics Belumosudil exposure-response relationships and the time course of pharmacodynamic response are not established. Cardiac Electrophysiology At 2.4 times the maximum exposure for approved recommended dose, REZUROCK does not prolong the QT interval to any clinically relevant extent.
12.3Pharmacokinetics The following pharmacokinetic parameters are presented for chronic GVHD patients administered belumosudil 200 mg once daily, unless otherwise specified. The mean (% coefficient of variation, %CV) steady-state AUC and C max of belumosudil was 22,700 (48%) h∙ng/mL and 2390 (44%) ng/mL, respectively. Belumosudil C max and AUC increased in an approximately proportional manner over a dosage range of 200 and 400 mg (1 to 2 times once daily recommended dosage).
The accumulation ratio of belumosudil was 1.4. Absorption Median T max of belumosudil at steady state was 1.26 to 2.53 hours following administration of 200 mg once daily or twice daily in patients. The mean (%CV) bioavailability was 64% (17%) following a single belumosudil dose in healthy subjects.
Effect of Food Belumosudil C max 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 approximately 50% of total caloric content of the meal from fat) compared to the fasted state in healthy subjects. Median T max was delayed 0.5 hours. Distribution The geometric mean volume of distribution after a single dose of belumosudil in healthy subjects was 184 L (geo CV% 67.7%).
Belumosudil binding to human serum albumin and human α 1 -acid glycoprotein was 99.9% and 98.6%, respectively, in vitro . Elimination The mean (%CV) elimination half-life of belumosudil was 19 hours (39%), and clearance was
9.83L/hours (46%) in patients. Metabolism Belumosudil is primarily metabolized by CYP3A and to a lesser extent by CYP2C8, CYP2D6, and UGT1A9, in vitro . Excretion Following a single oral dose of radiolabeled belumosudil in healthy subjects, 85% of radioactivity was recovered in feces (30% as unchanged) and less than 5% in urine.
Specific Populations No clinically significant differences in belumosudil pharmacokinetics were observed with regard to age (18 to 77 years), sex, weight (38.6 to 143 kg), or mild to moderate renal impairment (eGFR ≥60 and <90 mL/min/1.72m 2 to eGFR ≥30 and <60 mL/min/1.72m 2 ). The effect of severe renal impairment on the pharmacokinetics of belumosudil has not been studied. Patients with Hepatic Impairment Following a single 200 mg dose of belumosudil, changes in belumosudil exposure in subjects with varying degrees of hepatic impairment based on Child-Pugh score without liver GVHD relative to subjects with normal hepatic function is shown in Table 4.
Table 4: Effect of Varying Degrees of Hepatic Impairment on Belumosudil Exposure Hepatic Impairment Category Changes in Belumosudil Exposure in Subjects with Hepatic Impairment Compared to Subjects with Normal Hepatic Function Total (Free + Bound) Concentrations Free Concentrations C max AUC C max AUC Mild (Child-Pugh A) 1.2-fold increase 1.4-fold increase 14% decrease 19% decrease Moderate (Child-Pugh B) 6% decrease 1.5-fold increase 12% decrease 1.4-fold increase Severe (Child-Pugh C) 1.3-fold increase 4.2-fold increase 5.4-fold increase 16-fold increase Drug Interaction Studies Clinical Studies and Model-Informed Approaches Pro…
🧬 Mechanism of Action ▾
12.1Mechanism 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.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING REZUROCK 200 mg tablets are supplied as pale yellow film-coated oblong tablets containing 200 mg of belumosudil (equivalent to 242.5 mg belumosudil mesylate). Each tablet is debossed with "KDM" on one side and "200" on the other side and is packaged as follows: 200 mg tablets in 30 count bottle: NDC 79802-200-30 Store at room temperature, 20°C to 25°C (68°F to 77°F); excursions permitted from 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Dispense to patient in original container only.
Store in original container to protect from moisture. Replace cap securely each time after opening. Do not discard desiccant.
📦 Storage and Handling ▾
Store at room temperature, 20°C to 25°C (68°F to 77°F); excursions permitted from 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Dispense to patient in original container only. Store in original container to protect from moisture. Replace cap securely each time after opening. Do not discard desiccant.
📋 Description ▾
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).
The chemical structure is as follows: Belumosudil mesylate is a yellow powder that is practically insoluble in water, slightly soluble in methanol and DMF and soluble in DMSO. REZUROCK tablets are for oral administration. Each tablet contains 200 mg of the free base equivalent to 242.5 mg of belumosudil mesylate.
The tablet also contains the following inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, hypromellose, magnesium stearate, and microcrystalline cellulose. The tablet film consists of polyethylene glycol, polyvinyl alcohol, talc, titanium dioxide and yellow iron oxide. Chemical Structure
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information). Embryo-fetal Toxicity: Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to inform their healthcare provider of a known or suspected pregnancy [see Warnings and Precautions (5.1) , Use in Specific Populations (8.1 , 8.3) ].
Advise females of reproductive potential to use effective contraceptive during treatment with REZUROCK and for one week after the last dose [see Warnings and Precautions (5.1) ]. Advise males with female partners of reproductive potential to use effective contraceptive during treatment with REZUROCK and for one week after the last dose [see Use in Specific Populations (8.3) ] . Lactation Advise women not to breastfeed during treatment with REZUROCK and for one week after the last dose [see Use in Specific Populations (8.2) ] .
Infertility Advise males and females of reproductive potential that REZUROCK may impair fertility [see Use in Specific Populations (8.3) ]. Administration Inform patients to take REZUROCK orally once daily with food according to their physician's instructions and that the oral dosage (tablets) should be swallowed whole with a glass of water, without cutting, crushing or chewing the tablets approximately the same time each day [see Dosage and Administration (2.1) ]. Advise patients that in the event of a missed daily dose of REZUROCK, it should be taken as soon as possible on the same day with a return to the normal schedule the following day.
Patients should not take extra doses to make up the missed dose [see Dosage and Administration (2.1) ]. Drug Interactions Advise patients to inform their health care providers of all concomitant medications, including prescription medicines, over-the-counter drugs, vitamins, and herbal products [see Drug Interactions (7) ] .