A once-daily oral tablet for patients with cGVHD1
Each pale-yellow oblong 200-mg tablet is debossed with “KDM” on one side and “200” on the other side.1
Not actual size.
The recommended dose of REZUROCK is 200 mg once daily administered orally1
- Inform patients that the REZUROCK tablet should be swallowed whole with a glass of water without cutting, crushing or chewing the tablet
- Advise patients to take REZUROCK at approximately the same time each day with a meal
- If the patient misses a dose of REZUROCK, instruct the patient not to take extra doses to make up for the missed dose
- Monitor total bilirubin, AST and ALT at least monthly (see below for details on when to hold or discontinue REZUROCK due to hepatotoxicity or other adverse reactions)
Recommended dose modifications for REZUROCK for adverse reactions1
| Adverse reaction | Severitya | REZUROCK dose modifications |
|---|---|---|
| Hepatotoxicity | Grade 3 AST or ALT (5x to 20x ULN) or Grade 2 bilirubin (1.5x to 3x 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 (>20x ULN) or Grade ≥3 bilirubin (>3x ULN) |  Discontinue REZUROCK permanently. |
|
| Other adverse reactions | Grade 3 | Hold REZUROCK until recovery to Grade 0-1, then resume REZUROCK at the recommended dose level. |
| Grade 4 | Discontinue REZUROCK permanently. |
| Adverse reaction: Hepatotoxicity |
|---|
| Severitya REZUROCK dose modifications Hold REZUROCK until recovery of bilirubin, AST and ALT to Grade 0-1, then resume REZUROCK at the recommended dose. |
| Severitya REZUROCK dose modifications Discontinue REZUROCK permanently. |
| Adverse reaction: Other |
| Severitya REZUROCK dose modifications Hold REZUROCK until recovery to Grade 0-1, then resume REZUROCK at the recommended dose level. |
| Severitya REZUROCK dose modifications Discontinue REZUROCK permanently. |
aBased on CTCAE v4.03.
Please see full Prescribing Information for additional guidance for other populations.
Considerations for patients with renal or hepatic impairment1
Renal impairment
Patients with mild or moderate renal impairment
- No clinically significant differences in REZUROCK pharmacokinetics observed (mild to moderate renal impairment was defined as eGFR ≥60 and <90 mL/min/1.72m2 to eGFR ≥30 and <60 mL/min/1.72m2)
Patients with severe renal impairment
- No data are available for patients with severe renal impairment
Hepatic impairment
Patients with moderate or severe hepatic impairment
- Avoid use in patients with moderate hepatic impairment (Child-Pugh B) or severe hepatic impairment (Child-Pugh C) without liver GVHD
Patients with mild hepatic impairment
- No dosage adjustment is recommended when administering REZUROCK to patients with mild hepatic impairment
Consider the risks and potential benefits before initiating treatment with REZUROCK.
Drug interactions1
Effect of other drugs on REZUROCK
- Proton Pump Inhibitors: Increase the dosage of REZUROCK to 200 mg twice daily when used concomitantly with proton pump inhibitors (eg, rabeprazole)
- Strong CYP3A Inducers: Increase the dosage of REZUROCK to 200 mg twice daily when used concomitantly with strong CYP3A inducers (eg, rifampin)
Effect of REZUROCK on other drugs
- BCRP Substrates: Avoid concomitant use with drugs that are BCRP substrates (eg, rosuvastatin) 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
- OATP1B1 Substrates: If used together, monitor patients more frequently for adverse reactions of these substrates (eg, rosuvastatin) and decrease the OATP1B1 substrates dosage(s) in accordance with the respective Prescribing Information
- Certain CYP1A2, CYP3A, P-gp or UGT1A1 Substrates: Avoid concomitant use of REZUROCK with drugs that are sensitive CYP1A2 substrates (eg, caffeine), sensitive CYP3A substrates (eg, midazolam), UGT1A1 substrates (eg, raltegravir) or P-gp substrates (eg, dabigatran), 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
Please see the full Prescribing Information for additional information on drug interactions.
Use in specific populations1
Pregnancy
- REZUROCK can cause fetal harm when administered to pregnant women
- Advise pregnant women of the potential risk to the fetus. Advise women of reproductive potential, and their male partners, to use effective contraception during treatment with REZUROCK and for 1 week after the last dose of REZUROCK
Lactation
- Because of the potential for serious adverse reactions from REZUROCK in the breastfed child, advise lactating women not to breastfeed during treatment with REZUROCK and for one week after the last dose
Pediatric use
- The safety and effectiveness of REZUROCK in pediatric patients aged <12 years have not been established
Geriatric use
- Of the 186 patients with cGVHD in clinical studies of REZUROCK, 26% were aged ≥65 years. No clinically meaningful differences in safety or effectiveness of REZUROCK were observed in comparison to younger patients
Renal impairment
- Treatment with REZUROCK has not been studied in patients with preexisting severe renal impairment. For patients with preexisting severe renal impairment, consider the risks and potential benefits before initiating treatment with REZUROCK
Hepatic impairment
- Avoid use in patients with moderate hepatic impairment (Child-Pugh B) or severe hepatic impairment (Child-Pugh C) without liver GVHD
Storage1
Store REZUROCK tablets at room temperature (68 °F to 77 °F [20 °C to 25 °C]) in the original container.
REZUROCK should be dispensed to the patient in the original container only. Store in original container to protect from moisture. Replace cap securely each time after opening. Do not discard desiccant.
HELP YOUR PATIENTS GET
STARTED ON REZUROCK.
ALT, alanine aminotransferase; AST, aspartate aminotransferase; BCRP, breast cancer resistance protein; cGVHD, chronic graft-versus-host disease; CTCAE, Common Terminology Criteria for Adverse Events; CYP1A2, cytochrome P450 family 1 subfamily A member 2; CYP3A, cytochrome P450 family 3 subfamily A; eGFR, estimated glomerular filtration rate; MOA, mechanism of action; OATP1B1, organic anion-transporting polypeptides 1B1; P-gp, permeability glycoprotein; complex locus; UGT1A1, uridine diphosphate glucuronosyltransferase family 1 member A1; ULN, upper limit of normal.
Reference: 1. REZUROCK. Package insert. Kadmon Pharmaceuticals, LLC.
INDICATION
IMPORTANT SAFETY INFORMATION
IMPORTANT SAFETY INFORMATION
INDICATION
REZUROCK® (belumosudil) 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.
IMPORTANT SAFETY INFORMATION
Warnings and Precautions
- Embryo-Fetal Toxicity: Based on findings in animals and its mechanism of action, REZUROCK can cause fetal harm when administered to a pregnant woman. 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
Adverse Reactions
- 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
- 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)
- Monitor total bilirubin, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) at least monthly
Drug Interactions
- Proton Pump Inhibitors: Belumosudil exhibits pH-dependent solubility. Concomitant use of REZUROCK with proton pump inhibitors decreases belumosudil exposure, which may reduce the efficacy of REZUROCK. Increase the dosage of REZUROCK when used concomitantly with proton pump inhibitors
- Strong CYP3A Inducers: Belumosudil is a CYP3A substrate. Concomitant use of REZUROCK with strong CYP3A inducers decreases belumosudil exposure which may reduce the efficacy of REZUROCK. Increase the dosage of REZUROCK when used concomitantly with strong CYP3A inducers
- 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, 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 - Certain CYP1A2 and CYP3A Substrates: Avoid concomitant use of REZUROCK with drugs that are sensitive CYP1A2 or CYP3A substrates, for which minimal concentration changes may lead to serious toxicities. If concomitant use cannot be avoided, decrease the CYP1A2 or CYP3A substrate dosage(s) in accordance with the respective Prescribing Information. Belumosudil is a CYP1A2 and CYP3A inhibitor. Concomitant use of REZUROCK with sensitive CYP1A2 substrates (e.g., caffeine) or CYP3A substrates (e.g., midazolam) is predicted to increase CYP1A2 or CYP3A substrate exposure, 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 avoided, decrease the UGT1A1 substrates dosage(s) in accordance with the respective Prescribing Information. Belumosudil is a UGT1A1 inhibitor. Concomitant use of REZUROCK with a UGT1A1 substrate decreased plasma concentrations of the glucuronide metabolite of the UGT1A1 substrate. Concomitant use of belumosudil with other UGT1A1 substrates may increase their plasma concentrations, which may increase the risk of adverse reactions related to these substrates
- Certain P-gp Substrates: Avoid concomitant use of REZUROCK with drugs that are P-gp substrates, for which minimal concentration changes may lead to serious toxicities. If concomitant use cannot be avoided, decrease the P-gp substrates dosage(s) in accordance with the respective Prescribing Information. Belumosudil is a P-gp inhibitor. Concomitant use of REZUROCK with P-gp substrates increased their plasma concentrations, which may increase the risk of adverse reactions related to these substrates
Use in Specific Populations
- Pregnancy: There are no available human data on REZUROCK use in pregnant women to evaluate for a drug-associated risk. Advise pregnant women and females of reproductive potential of the potential risk to the fetus
- Lactation: 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
- Pediatric Use: The safety and effectiveness of REZUROCK in pediatric patients less than 12 years old have not been established
- Geriatric 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
- Renal Impairment: 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
- Hepatic Impairment: Avoid use in patients with moderate hepatic impairment (Child-Pugh B) or severe hepatic impairment (Child-Pugh C) without liver GVHD. No dose adjustment is recommended for patients with mild hepatic impairment (Child-Pugh A)
Please click here for full Prescribing Information.
IMPORTANT SAFETY INFORMATION
Warnings and Precautions
- Embryo-Fetal Toxicity: Based on findings in animals and its mechanism of action, REZUROCK can cause fetal harm when administered to a pregnant woman. 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
Adverse Reactions
- 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
- 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)
- Monitor total bilirubin, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) at least monthly
Drug Interactions
- Proton Pump Inhibitors: Belumosudil exhibits pH-dependent solubility. Concomitant use of REZUROCK with proton pump inhibitors decreases belumosudil exposure, which may reduce the efficacy of REZUROCK. Increase the dosage of REZUROCK when used concomitantly with proton pump inhibitors
- Strong CYP3A Inducers: Belumosudil is a CYP3A substrate. Concomitant use of REZUROCK with strong CYP3A inducers decreases belumosudil exposure which may reduce the efficacy of REZUROCK. Increase the dosage of REZUROCK when used concomitantly with strong CYP3A inducers
- 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, 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 - Certain CYP1A2 and CYP3A Substrates: Avoid concomitant use of REZUROCK with drugs that are sensitive CYP1A2 or CYP3A substrates, for which minimal concentration changes may lead to serious toxicities. If concomitant use cannot be avoided, decrease the CYP1A2 or CYP3A substrate dosage(s) in accordance with the respective Prescribing Information. Belumosudil is a CYP1A2 and CYP3A inhibitor. Concomitant use of REZUROCK with sensitive CYP1A2 substrates (e.g., caffeine) or CYP3A substrates (e.g., midazolam) is predicted to increase CYP1A2 or CYP3A substrate exposure, 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 avoided, decrease the UGT1A1 substrates dosage(s) in accordance with the respective Prescribing Information. Belumosudil is a UGT1A1 inhibitor. Concomitant use of REZUROCK with a UGT1A1 substrate decreased plasma concentrations of the glucuronide metabolite of the UGT1A1 substrate. Concomitant use of belumosudil with other UGT1A1 substrates may increase their plasma concentrations, which may increase the risk of adverse reactions related to these substrates
- Certain P-gp Substrates: Avoid concomitant use of REZUROCK with drugs that are P-gp substrates, for which minimal concentration changes may lead to serious toxicities. If concomitant use cannot be avoided, decrease the P-gp substrates dosage(s) in accordance with the respective Prescribing Information. Belumosudil is a P-gp inhibitor. Concomitant use of REZUROCK with P-gp substrates increased their plasma concentrations, which may increase the risk of adverse reactions related to these substrates
Use in Specific Populations
- Pregnancy: There are no available human data on REZUROCK use in pregnant women to evaluate for a drug-associated risk. Advise pregnant women and females of reproductive potential of the potential risk to the fetus
- Lactation: 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
- Pediatric Use: The safety and effectiveness of REZUROCK in pediatric patients less than 12 years old have not been established
- Geriatric 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
- Renal Impairment: 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
- Hepatic Impairment: Avoid use in patients with moderate hepatic impairment (Child-Pugh B) or severe hepatic impairment (Child-Pugh C) without liver GVHD. No dose adjustment is recommended for patients with mild hepatic impairment (Child-Pugh A)
Please click here for full Prescribing Information.
INDICATION
REZUROCK® (belumosudil) 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.
IMPORTANT SAFETY INFORMATION
INDICATION
REZUROCK® (belumosudil) 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.
IMPORTANT SAFETY INFORMATION
Warnings and Precautions
- Embryo-Fetal Toxicity: Based on findings in animals and its mechanism of action, REZUROCK can cause fetal harm when administered to a pregnant woman. 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
Adverse Reactions
- 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
- 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)
- Monitor total bilirubin, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) at least monthly
Drug Interactions
- Proton Pump Inhibitors: Belumosudil exhibits pH-dependent solubility. Concomitant use of REZUROCK with proton pump inhibitors decreases belumosudil exposure, which may reduce the efficacy of REZUROCK. Increase the dosage of REZUROCK when used concomitantly with proton pump inhibitors
- Strong CYP3A Inducers: Belumosudil is a CYP3A substrate. Concomitant use of REZUROCK with strong CYP3A inducers decreases belumosudil exposure which may reduce the efficacy of REZUROCK. Increase the dosage of REZUROCK when used concomitantly with strong CYP3A inducers
- 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, 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 - Certain CYP1A2 and CYP3A Substrates: Avoid concomitant use of REZUROCK with drugs that are sensitive CYP1A2 or CYP3A substrates, for which minimal concentration changes may lead to serious toxicities. If concomitant use cannot be avoided, decrease the CYP1A2 or CYP3A substrate dosage(s) in accordance with the respective Prescribing Information. Belumosudil is a CYP1A2 and CYP3A inhibitor. Concomitant use of REZUROCK with sensitive CYP1A2 substrates (e.g., caffeine) or CYP3A substrates (e.g., midazolam) is predicted to increase CYP1A2 or CYP3A substrate exposure, 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 avoided, decrease the UGT1A1 substrates dosage(s) in accordance with the respective Prescribing Information. Belumosudil is a UGT1A1 inhibitor. Concomitant use of REZUROCK with a UGT1A1 substrate decreased plasma concentrations of the glucuronide metabolite of the UGT1A1 substrate. Concomitant use of belumosudil with other UGT1A1 substrates may increase their plasma concentrations, which may increase the risk of adverse reactions related to these substrates
- Certain P-gp Substrates: Avoid concomitant use of REZUROCK with drugs that are P-gp substrates, for which minimal concentration changes may lead to serious toxicities. If concomitant use cannot be avoided, decrease the P-gp substrates dosage(s) in accordance with the respective Prescribing Information. Belumosudil is a P-gp inhibitor. Concomitant use of REZUROCK with P-gp substrates increased their plasma concentrations, which may increase the risk of adverse reactions related to these substrates
Use in Specific Populations
- Pregnancy: There are no available human data on REZUROCK use in pregnant women to evaluate for a drug-associated risk. Advise pregnant women and females of reproductive potential of the potential risk to the fetus
- Lactation: 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
- Pediatric Use: The safety and effectiveness of REZUROCK in pediatric patients less than 12 years old have not been established
- Geriatric 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
- Renal Impairment: 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
- Hepatic Impairment: Avoid use in patients with moderate hepatic impairment (Child-Pugh B) or severe hepatic impairment (Child-Pugh C) without liver GVHD. No dose adjustment is recommended for patients with mild hepatic impairment (Child-Pugh A)
Please click here for full Prescribing Information.
IMPORTANT SAFETY INFORMATION
Warnings and Precautions
- Embryo-Fetal Toxicity: Based on findings in animals and its mechanism of action, REZUROCK can cause fetal harm when administered to a pregnant woman. 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
Adverse Reactions
- 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
- 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)
- Monitor total bilirubin, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) at least monthly
Drug Interactions
- Proton Pump Inhibitors: Belumosudil exhibits pH-dependent solubility. Concomitant use of REZUROCK with proton pump inhibitors decreases belumosudil exposure, which may reduce the efficacy of REZUROCK. Increase the dosage of REZUROCK when used concomitantly with proton pump inhibitors
- Strong CYP3A Inducers: Belumosudil is a CYP3A substrate. Concomitant use of REZUROCK with strong CYP3A inducers decreases belumosudil exposure which may reduce the efficacy of REZUROCK. Increase the dosage of REZUROCK when used concomitantly with strong CYP3A inducers
- 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, 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 - Certain CYP1A2 and CYP3A Substrates: Avoid concomitant use of REZUROCK with drugs that are sensitive CYP1A2 or CYP3A substrates, for which minimal concentration changes may lead to serious toxicities. If concomitant use cannot be avoided, decrease the CYP1A2 or CYP3A substrate dosage(s) in accordance with the respective Prescribing Information. Belumosudil is a CYP1A2 and CYP3A inhibitor. Concomitant use of REZUROCK with sensitive CYP1A2 substrates (e.g., caffeine) or CYP3A substrates (e.g., midazolam) is predicted to increase CYP1A2 or CYP3A substrate exposure, 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 avoided, decrease the UGT1A1 substrates dosage(s) in accordance with the respective Prescribing Information. Belumosudil is a UGT1A1 inhibitor. Concomitant use of REZUROCK with a UGT1A1 substrate decreased plasma concentrations of the glucuronide metabolite of the UGT1A1 substrate. Concomitant use of belumosudil with other UGT1A1 substrates may increase their plasma concentrations, which may increase the risk of adverse reactions related to these substrates
- Certain P-gp Substrates: Avoid concomitant use of REZUROCK with drugs that are P-gp substrates, for which minimal concentration changes may lead to serious toxicities. If concomitant use cannot be avoided, decrease the P-gp substrates dosage(s) in accordance with the respective Prescribing Information. Belumosudil is a P-gp inhibitor. Concomitant use of REZUROCK with P-gp substrates increased their plasma concentrations, which may increase the risk of adverse reactions related to these substrates
Use in Specific Populations
- Pregnancy: There are no available human data on REZUROCK use in pregnant women to evaluate for a drug-associated risk. Advise pregnant women and females of reproductive potential of the potential risk to the fetus
- Lactation: 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
- Pediatric Use: The safety and effectiveness of REZUROCK in pediatric patients less than 12 years old have not been established
- Geriatric 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
- Renal Impairment: 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
- Hepatic Impairment: Avoid use in patients with moderate hepatic impairment (Child-Pugh B) or severe hepatic impairment (Child-Pugh C) without liver GVHD. No dose adjustment is recommended for patients with mild hepatic impairment (Child-Pugh A)
Please click here for full Prescribing Information.
INDICATION
REZUROCK® (belumosudil) 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.
IMPORTANT SAFETY INFORMATION
INDICATION
REZUROCK® (belumosudil) 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.
IMPORTANT SAFETY INFORMATION
Warnings and Precautions
- Embryo-Fetal Toxicity: Based on findings in animals and its mechanism of action, REZUROCK can cause fetal harm when administered to a pregnant woman. 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
Adverse Reactions
- 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
- 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)
- Monitor total bilirubin, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) at least monthly
Drug Interactions
- Proton Pump Inhibitors: Belumosudil exhibits pH-dependent solubility. Concomitant use of REZUROCK with proton pump inhibitors decreases belumosudil exposure, which may reduce the efficacy of REZUROCK. Increase the dosage of REZUROCK when used concomitantly with proton pump inhibitors
- Strong CYP3A Inducers: Belumosudil is a CYP3A substrate. Concomitant use of REZUROCK with strong CYP3A inducers decreases belumosudil exposure which may reduce the efficacy of REZUROCK. Increase the dosage of REZUROCK when used concomitantly with strong CYP3A inducers
- 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, 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 - Certain CYP1A2 and CYP3A Substrates: Avoid concomitant use of REZUROCK with drugs that are sensitive CYP1A2 or CYP3A substrates, for which minimal concentration changes may lead to serious toxicities. If concomitant use cannot be avoided, decrease the CYP1A2 or CYP3A substrate dosage(s) in accordance with the respective Prescribing Information. Belumosudil is a CYP1A2 and CYP3A inhibitor. Concomitant use of REZUROCK with sensitive CYP1A2 substrates (e.g., caffeine) or CYP3A substrates (e.g., midazolam) is predicted to increase CYP1A2 or CYP3A substrate exposure, 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 avoided, decrease the UGT1A1 substrates dosage(s) in accordance with the respective Prescribing Information. Belumosudil is a UGT1A1 inhibitor. Concomitant use of REZUROCK with a UGT1A1 substrate decreased plasma concentrations of the glucuronide metabolite of the UGT1A1 substrate. Concomitant use of belumosudil with other UGT1A1 substrates may increase their plasma concentrations, which may increase the risk of adverse reactions related to these substrates
- Certain P-gp Substrates: Avoid concomitant use of REZUROCK with drugs that are P-gp substrates, for which minimal concentration changes may lead to serious toxicities. If concomitant use cannot be avoided, decrease the P-gp substrates dosage(s) in accordance with the respective Prescribing Information. Belumosudil is a P-gp inhibitor. Concomitant use of REZUROCK with P-gp substrates increased their plasma concentrations, which may increase the risk of adverse reactions related to these substrates
Use in Specific Populations
- Pregnancy: There are no available human data on REZUROCK use in pregnant women to evaluate for a drug-associated risk. Advise pregnant women and females of reproductive potential of the potential risk to the fetus
- Lactation: 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
- Pediatric Use: The safety and effectiveness of REZUROCK in pediatric patients less than 12 years old have not been established
- Geriatric 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
- Renal Impairment: 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
- Hepatic Impairment: Avoid use in patients with moderate hepatic impairment (Child-Pugh B) or severe hepatic impairment (Child-Pugh C) without liver GVHD. No dose adjustment is recommended for patients with mild hepatic impairment (Child-Pugh A)
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IMPORTANT SAFETY INFORMATION
Warnings and Precautions
- Embryo-Fetal Toxicity: Based on findings in animals and its mechanism of action, REZUROCK can cause fetal harm when administered to a pregnant woman. 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
Adverse Reactions
- 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
- 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)
- Monitor total bilirubin, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) at least monthly
Drug Interactions
- Proton Pump Inhibitors: Belumosudil exhibits pH-dependent solubility. Concomitant use of REZUROCK with proton pump inhibitors decreases belumosudil exposure, which may reduce the efficacy of REZUROCK. Increase the dosage of REZUROCK when used concomitantly with proton pump inhibitors
- Strong CYP3A Inducers: Belumosudil is a CYP3A substrate. Concomitant use of REZUROCK with strong CYP3A inducers decreases belumosudil exposure which may reduce the efficacy of REZUROCK. Increase the dosage of REZUROCK when used concomitantly with strong CYP3A inducers
- 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, 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 - Certain CYP1A2 and CYP3A Substrates: Avoid concomitant use of REZUROCK with drugs that are sensitive CYP1A2 or CYP3A substrates, for which minimal concentration changes may lead to serious toxicities. If concomitant use cannot be avoided, decrease the CYP1A2 or CYP3A substrate dosage(s) in accordance with the respective Prescribing Information. Belumosudil is a CYP1A2 and CYP3A inhibitor. Concomitant use of REZUROCK with sensitive CYP1A2 substrates (e.g., caffeine) or CYP3A substrates (e.g., midazolam) is predicted to increase CYP1A2 or CYP3A substrate exposure, 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 avoided, decrease the UGT1A1 substrates dosage(s) in accordance with the respective Prescribing Information. Belumosudil is a UGT1A1 inhibitor. Concomitant use of REZUROCK with a UGT1A1 substrate decreased plasma concentrations of the glucuronide metabolite of the UGT1A1 substrate. Concomitant use of belumosudil with other UGT1A1 substrates may increase their plasma concentrations, which may increase the risk of adverse reactions related to these substrates
- Certain P-gp Substrates: Avoid concomitant use of REZUROCK with drugs that are P-gp substrates, for which minimal concentration changes may lead to serious toxicities. If concomitant use cannot be avoided, decrease the P-gp substrates dosage(s) in accordance with the respective Prescribing Information. Belumosudil is a P-gp inhibitor. Concomitant use of REZUROCK with P-gp substrates increased their plasma concentrations, which may increase the risk of adverse reactions related to these substrates
Use in Specific Populations
- Pregnancy: There are no available human data on REZUROCK use in pregnant women to evaluate for a drug-associated risk. Advise pregnant women and females of reproductive potential of the potential risk to the fetus
- Lactation: 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
- Pediatric Use: The safety and effectiveness of REZUROCK in pediatric patients less than 12 years old have not been established
- Geriatric 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
- Renal Impairment: 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
- Hepatic Impairment: Avoid use in patients with moderate hepatic impairment (Child-Pugh B) or severe hepatic impairment (Child-Pugh C) without liver GVHD. No dose adjustment is recommended for patients with mild hepatic impairment (Child-Pugh A)
Please click here for full Prescribing Information.
INDICATION
REZUROCK® (belumosudil) 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.