View in Browser | Prescribing Information

IMPORTANT SAFETY INFORMATION

Warnings & Precautions

lschemic Heart Disease – In a study of patients with mHSPC (ARASENS), ischemic heart disease occurred in 3.2% of patients receiving NUBEQA with docetaxel versus 2% receiving placebo with docetaxel, including Grade 3-4 events in 1.3% vs. 1.1%, respectively.

See additional Important Safety Information below

NUBEQA (darolutamide) + Docetaxel DELIVERS SURVIVAL BENEFITS WITH PROVEN TOLERABILITY1,2

Tolerability may be an important consideration when selecting treatment for your patient with mHSPC. Choose NUBEQA first for powerful efficacy and proven tolerability.1,2

INDICATION

NUBEQA® (darolutamide) is an androgen receptor inhibitor indicated for the treatment of adult patients with metastatic hormone-sensitive prostate cancer (mHSPC) in combination with docetaxel.

The NUBEQA combination* significantly reduced the risk of death by nearly a third1,2

ARASENS Study Design and Select Data: 1305 mHSPC patients on ADT† with docetaxel who received ADT within 12 weeks before study entry were randomized 1:1 and treated with concurrent 600 mg NUBEQA twice daily (n=651) or placebo (n=654) in a multicenter, double-blind, phase Ill trial. Treatment with NUBEQA or placebo continued until symptomatic progressive disease, change of antineoplastic therapy, or unacceptable toxicity. Concomitant docetaxel was administered at 75 mg/m2 every 21 days for 6 cycles within 6 weeks of starting NUBEQA or placebo. OS was the primary endpoint and OS was statistically significant for the NUBEQA arm vs placebo; HR: 0.68; 95% Cl: 0.57-0.80; P<0.0001.1,2

*NUBEQA combination = NUBEQA + ADT + docetaxel.

†Concomitant GnRH analog or prior bilateral orchiectomy.

TOLERABILITY: Permanent discontinuation of NUBEQA due to adverse reactions occurred in 14% of patients receiving NUBEQA. Dose interruptions due to adverse reactions occurred in 23% of patients treated with NUBEQA. Dose reductions due to adverse reactions occurred in 9% of patients treated with NUBEQA.1,2

•

No substantial increases in adverse reactions with NUBEQA + docetaxel vs placebo + docetaxel1-3

‡AEs per NCI-CTAE v4.03.3

§Rash includes rash, rash maculo-papular, palmar-plantar erythrodysesthesia syndrome, eczema, dermatitis, skin exfoliation, dermatitis acneiform, drug eruption, rash pruritic, rash erythematous, erythema multiforme, rash macular, dermatitis exfoliative generalized, penile rash, dyshidrotic eczema, rash papular, dermatitis bullous, rash follicular, rash pustular, rash vesicular, toxic skin eruption.

¶Hemorrhage includes hematuria, epistaxis, anal hemorrhage, hemorrhoidal hemorrhage, rectal hemorrhage, upper gastrointestinal hemorrhage, hemoptysis, hemorrhage urinary tract, hemorrhagic stroke, subarachnoid hemorrhage, lower gastrointestinal hemorrhage, cystitis hemorrhagic, gastrointestinal hemorrhage, hemorrhage subcutaneous, intra-abdominal hemorrhage, nail bed bleeding, subdural hemorrhage.

||Hypertension includes hypertension, blood pressure increased, and hypertensive emergency and hypertensive crisis.

Additional Safety Results1

•

Serious adverse reactions occurred in 45% of patients receiving NUBEQA with docetaxel vs 42% of patients receiving placebo with docetaxel. Serious adverse reactions in ≥2% of patients who received NUBEQA with docetaxel included febrile neutropenia (6%), neutrophil count decreased (2.8%), musculoskeletal pain (2.6%), and pneumonia (2.6%)

•

Fatal adverse reactions occurred in 4% of patients receiving NUBEQA with docetaxel vs 4% of patients receiving placebo with docetaxel. Fatal adverse reactions in patients who received NUBEQA included COVID-19/COVID-19 pneumonia (0.8%), myocardial infarction (0.3%), and sudden death (0.3%)

•

Clinically relevant adverse reactions in <10% of patients who received NUBEQA with docetaxel included fractures (8%), ischemic heart disease (2.9%), seizures (0.6%), and drug-induced liver injury (0.3%)

•

Permanent discontinuation of NUBEQA due to adverse reactions occurred in 14% of patients receiving NUBEQA. Dose interruptions due to adverse reactions occurred in 23% of patients treated with NUBEQA. Dose reductions due to adverse reactions occurred in 9% of patients treated with NUBEQA

See additional Important Safety Information below

ADT=androgen deprivation therapy; AE=adverse event; ALT=alanine aminotransferase; AST=aspartate aminotransferase; DDI=drug-drug interaction; mHSPC=metastatic hormone-sensitive prostate cancer; NCI-CTCAE=National Cancer Institute Common Terminology Criteria for Adverse Events.

See additional Important Safety Information below

Drug interactions with concomitant use of NUBEQA

•

Administration of NUBEQA in combination with docetaxel resulted in no clinically relevant changes in the pharmacokinetics of docetaxel in patients with mHSPC. There were also no clinically relevant changes in the pharmacokinetics of NUBEQA when used in combination with docetaxel1

NEARLY ALL PATIENTS WITH mHSPC are on concomitant medications, so choose an aRI with limited ddis2

#Decreases darolutamide exposure, which may decrease NUBEQA activity.

**Increases darolutamide exposure, which may increase the risk of NUBEQA adverse reactions.

††Increases BCRP substrate exposure, which may increase the risk of related toxicities. Consult the approved product labeling of the BCRP substrate when used concomitantly with NUBEQA.

‡‡Concomitant use of NUBEQA may increase the plasma concentrations of OATP1B1 or OATP1B3 substrates.

ADT=androgen deprivation therapy; BCRP=breast cancer resistance protein; CI=confidence interval; CYP3A4=cytochrome P450 3A4 subtype; DDIs=drug-drug interactions; GnRH=gonadotropin-releasing hormone; HR=hazard ratio; OATP1B1=organic anion transporter polypeptide 1B1; OATP1B3=organic anion transporter polypeptide 1B3; OS=overall survival; P-gp=P-glycoprotein.

IMPORTANT SAFETY INFORMATION

Warnings & Precautions

Ischemic Heart Disease – In a study of patients with mHSPC (ARASENS), ischemic heart disease occurred in 3.2% of patients receiving NUBEQA with docetaxel versus 2% receiving placebo with docetaxel, including Grade 3-4 events in 1.3% vs. 1.1%, respectively. Ischemic events led to death in 0.3% of patients receiving NUBEQA with docetaxel vs. 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.

Seizure – In ARASENS, seizure occurred in 0.6% of patients receiving NUBEQA with docetaxel, including one Grade 3 event, vs. 0.2% receiving placebo with docetaxel. Seizure occurred 38 to 340 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.

Embryo-Fetal Toxicity – Safety and efficacy of NUBEQA have not been established in females. NUBEQA can cause fetal harm and loss of pregnancy. Advise males with female partners of reproductive potential to use effective contraception during treatment with NUBEQA and for 1 week after the last dose.

Adverse Reactions

In ARASENS, serious adverse reactions occurred in 45% of patients receiving NUBEQA with docetaxel vs. 42% of patients receiving placebo with docetaxel. Serious adverse reactions in ≥2% of patients who received NUBEQA with docetaxel included febrile neutropenia (6%), decreased neutrophil count (2.8%), musculoskeletal pain (2.6%), and pneumonia (2.6%). Fatal adverse reactions occurred in 4% of patients receiving NUBEQA with docetaxel vs. 4% of patients receiving placebo with docetaxel. Fatal adverse reactions in patients who received NUBEQA included COVID-19/COVID-19 pneumonia (0.8%), myocardial infarction (0.3%), and sudden death (0.3%). The most common adverse reactions (≥10% with a ≥2% increase over placebo with docetaxel) were constipation, rash, decreased appetite, hemorrhage, increased weight, and hypertension. The most common laboratory test abnormalities (≥30%) were anemia, hyperglycemia, decreased lymphocyte count, decreased neutrophil count, increased AST, increased ALT, and hypocalcemia. Clinically relevant adverse reactions in <10% of patients who received NUBEQA with docetaxel included fractures, ischemic heart disease, seizures, and drug-induced liver injury.

Drug Interactions

Effect of Other Drugs on NUBEQA – Combined P-gp and strong or moderate CYP3A4 inducers decrease NUBEQA exposure, which may decrease NUBEQA activity. Avoid concomitant use.

Combined P-gp and strong CYP3A4 inhibitors increase NUBEQA exposure, which may increase the risk of NUBEQA adverse reactions. Monitor more frequently and modify NUBEQA dose as needed.

Effects of NUBEQA on Other Drugs – NUBEQA inhibits breast cancer resistance protein (BCRP) transporter. Concomitant use increases exposure (AUC) and maximal concentration of BCRP substrates, which may increase the risk of BCRP substrate-related toxicities. Avoid concomitant use where possible. If used together, monitor more frequently for adverse reactions, and consider dose reduction of the BCRP substrate.

NUBEQA inhibits OATP1B1 and OATP1B3 transporters. Concomitant use may increase plasma concentrations of OATP1B1 or OATP1B3 substrates. Monitor more frequently for adverse reactions and consider dose reduction of these substrates.

Review the Prescribing Information of drugs that are BCRP, OATP1B1, and OATP1B3 substrates when used concomitantly with NUBEQA.

For important risk and use information about NUBEQA, please see the full Prescribing Information.

You are encouraged to report side effects or quality complaints of products to the FDA by visiting www.fda.gov/medwatch or calling 1-‌800-‌FDA-‌1088. For Bayer products, you can report these directly to Bayer by clicking here.

References: 1. NUBEQA (darolutamide) [prescribing information]. Whippany, NJ: Bayer HealthCare Pharmaceuticals, Inc.; October 2023. 2. Smith MR, Hussain M, Saad F, et al; ARASENS Trial Investigators. Darolutamide and survival in metastatic, hormone-sensitive prostate cancer. N Engl J Med. 2022;386(12):1132-1142. 3. Data on file. Bayer HealthCare Pharmaceuticals, Inc: Whippany, NJ. 4. University of Washington Pharmacy Services. Anticoagulation Services. Rivaroxaban Drug Interaction Potential. https://depts.washington.edu/anticoag/home/content/rivaroxaban-drug-interaction-potential. Accessed May 5, 2022. 5. D‌A‌.g‌o‌v‌. Center for Drug Evaluation and Research. Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers. U.S. Food and Drug Administration. https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers. Accessed May 5, 2022. 6. Kalliokoski A, Niemi M. Impact of OATP transporters on pharmacokinetics. Br J Pharmacol. 2009;158(3):693-705.

Please note that this email address is not monitored for replies. If you would like to contact us, visit our Contact Us section online.

100‌ Bayer Boulevard‌, PO Box 915‌, Whippany‌, NJ 07981-0915‌

BAYER, the Bayer Cross and NUBEQA are registered
trademarks of Bayer.

PP‌-NUB‌-US‌-3042‌-1 03/24‌

Conditions of Use | Privacy Statement

This message is brought to you by Bayer's Pharmaceutical Division.

This content is sponsored by Bayer, and ION Oncology Practice Network has not independently reviewed or verified the information provided by Bayer.

This email was sent to karleigh.bard-marsh@cencora.com because you have an account with or are a valued partner of Cencora Specialty GPOs | ION Oncology Practice Network. If you no longer wish to receive these types of emails, please click here to unsubscribe or update your email preferences.