DAROLUTAMIDE Drug Interactions: What You Need to Know

INTERACTIONS Combined P-gp and Strong or Moderate CYP3A Inducers : Avoid concomitant use. ( 7.1 ) Combined P-gp and Strong CYP3A Inhibitors : Monitor patients more frequently for NUBEQA adverse reactions. ( 7.1 )

Bcrp

Substrates : Avoid concomitant use with drugs that are BCRP substrates where possible. If used together, monitor patients more frequently for adverse reactions and consider dose reduction of the BCRP substrate drug. ( 7.2 ) OATP1B1 and OATP1B3 Substrates : Concomitant use of NUBEQA may increase the plasma concentrations of OATP1B1 or OATP1B3 substrates. If used together, monitor patients more frequently for adverse reactions and consider dose reduction of these drugs. ( 7.2 )

7.1 Effects of Other Drugs on NUBEQA Combined P-gp and Strong or Moderate CYP3A4 Inducer Concomitant use of NUBEQA with a combined P-gp and strong or moderate CYP3A4 inducer decreases darolutamide exposure which may decrease NUBEQA activity <span class="opacity-50 text-xs">[see Clinical Pharmacology (12.3) ]</span> . Avoid concomitant use of NUBEQA with combined P-gp and strong or moderate CYP3A4 inducers. Combined P-gp and Strong CYP3A4 Inhibitors Concomitant use of NUBEQA with a combined P-gp and strong CYP3A4 inhibitor increases darolutamide exposure <span class="opacity-50 text-xs">[see Clinical Pharmacology (12.3) ]</span> which may increase the risk of NUBEQA adverse reactions . Monitor patients more frequently for NUBEQA adverse reactions and modify NUBEQA dosage as needed <span class="opacity-50 text-xs">[see Dosage and Administration (2.2) ]</span> .

7.2 Effects of NUBEQA on Other Drugs Breast Cancer Resistance Protein (BCRP) and Organic Anion Transporting Polypeptides (OATP) 1B1 and 1B3 Substrates NUBEQA is an inhibitor of BCRP transporter. Concomitant use of NUBEQA increases the AUC and C max of BCRP substrates <span class="opacity-50 text-xs">[see Clinical Pharmacology (12.3) ]</span>, which may increase the risk of BCRP substrate-related toxicities. Avoid concomitant use with drugs that are BCRP substrates where possible. If used together, monitor patients more frequently for adverse reactions, and consider dose reduction of the BCRP substrate drug. NUBEQA is an inhibitor of OATP1B1 and OATP1B3 transporters. Concomitant use of NUBEQA may increase the plasma concentrations of OATP1B1 or OATP1B3 substrates. Monitor patients more frequently for adverse reactions of these drugs and consider dose reduction while patients are taking NUBEQA <span class="opacity-50 text-xs">[see Clinical Pharmacology (12.3) ]</span> , Review the prescribing information of the BCRP, OATP1B1 and OATP1B3 substrates when used concomitantly with NUBEQA.

None. None. ( 4 )

AND PRECAUTIONS Ischemic Heart Disease : Optimize management of cardiovascular risk factors. Monitor for signs and symptoms of coronary artery disease. Discontinue NUBEQA for Grade 3-4 events. ( 5.1 ) Seizure : Consider discontinuation of NUBEQA in patients who develop a seizure during treatment. ( 5.2 ) Embryo-Fetal Toxicity : NUBEQA can cause fetal harm and loss of pregnancy. Advise males with female partners of reproductive potential to use effective contraception. ( 5.3 , 8.1 , 8.3 )

5.1 Ischemic Heart Disease Ischemic heart disease, including fatal cases, occurred in patients receiving NUBEQA. In a pooled analysis of ARAMIS and ARANOTE, ischemic heart disease occurred in 3.4% of patients receiving NUBEQA and 2.2% receiving placebo, including Grade 3-4 events in 1.4% and 0.3%, respectively. Ischemic events led to death in 0.4% of patients receiving NUBEQA and 0.4% receiving placebo. In ARASENS, ischemic heart disease occurred in 3.2% of patients receiving NUBEQA with docetaxel and 2% receiving placebo with docetaxel, including Grade 3-4 events in 1.3% and 1.1%, respectively. Ischemic events led to death in 0.3% of patients receiving NUBEQA with docetaxel and 0% receiving placebo with docetaxel. Monitor for signs and symptoms of ischemic heart disease. Optimize management of cardiovascular risk factors, such as hypertension, diabetes, or dyslipidemia. Discontinue NUBEQA for Grade 3-4 ischemic heart disease.

5.2 Seizure Seizure occurred in patients receiving NUBEQA. In a pooled analysis of ARAMIS and ARANOTE, Grade 1-3 seizure occurred in 0.2% of patients receiving NUBEQA. Seizure occurred from 261 to 665 days after initiation of NUBEQA. In ARASENS, seizure occurred in 0.8% of patients receiving NUBEQA with docetaxel, including two Grade 3 events. Seizure occurred from 38 to 1754 days after initiation of NUBEQA. It is unknown whether anti-epileptic medications will prevent seizures with NUBEQA. Advise patients of the risk of developing a seizure while receiving NUBEQA and of engaging in any activity where sudden loss of consciousness could cause harm to themselves or others. Consider discontinuation of NUBEQA in patients who develop a seizure during treatment.

5.3 Embryo-Fetal Toxicity The safety and efficacy of NUBEQA have not been established in females. Based on its mechanism of action, NUBEQA can cause fetal harm and loss of pregnancy when administered to a pregnant female <span class="opacity-50 text-xs">[see Clinical Pharmacology (12.1) ]</span> . Advise males with female partners of reproductive potential to use effective contraception during treatment and for 1 week after the last dose of NUBEQA <span class="opacity-50 text-xs">[see Use in Specific Populations (8.1 , 8.3) ]</span> .