BELUMOSUDIL Drug Interactions: What You Need to Know

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 )

7.1 Effect of Other Drugs on REZUROCK Proton Pump Inhibitors Belumosudil exhibits pH-dependent solubility. Concomitant use of REZUROCK with proton pump inhibitors decreases belumosudil exposure <span class="opacity-50 text-xs">[see Clinical Pharmacology (12.3) ]</span> , which may reduce the efficacy of REZUROCK. Increase the dosage of REZUROCK when used concomitantly with proton pump inhibitors <span class="opacity-50 text-xs">[see Dosage and Administration (2.3) ]</span>. Strong CYP3A Inducers Belumosudil is a CYP3A substrate. Concomitant use of REZUROCK with strong CYP3A inducers decreases belumosudil exposure <span class="opacity-50 text-xs">[see Clinical Pharmacology (12.3) ]</span> , which may reduce the efficacy of REZUROCK. Increase the dosage of REZUROCK when used concomitantly with strong CYP3A inducers <span class="opacity-50 text-xs">[see Dosage and Administration (2.3) ]</span>.

7.2 Effect 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 <span class="opacity-50 text-xs">[see Clinical Pharmacology (12.3) ]</span> , 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 <span class="opacity-50 text-xs">[see Clinical Pharmacology (12.3) ]</span> . 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 <span class="opacity-50 text-xs">[see Clinical Pharmacology (12.3) ]</span> , 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 <span class="opacity-50 text-xs">[see Clinical Pharmacology (12.3) ]</span> , 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 <span class="opacity-50 text-xs">[see Clinical Pharmacology (12.3) ]</span>. 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 <span class="opacity-50 text-xs">[see Clinical Pharmacology (12.3) ]</span> , which may increase the risk of adverse reactions related to these substrates.

None. None. ( 4 )

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 )

5.1 Embryo-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 <span class="opacity-50 text-xs">[see Use in Specific Populations (8.1 , 8.3) , Nonclinical Toxicology (13.1) ]</span> .