ERLEADA

Dosage and Administration ( 2.1 , 2.2 , 2.3 ) 03/2026 Warnings and Precautions ( 5.8 ) 06/2026

1 INDICATIONS AND USAGE ERLEADA is indicated for the treatment of patients with Metastatic castration-sensitive prostate cancer (mCSPC) Non-metastatic castration-resistant prostate cancer (nmCRPC) ERLEADA is an androgen receptor inhibitor indicated for the treatment of patients with metastatic castration-sensitive prostate cancer. ( 1 ) non-metastatic castration-resistant prostate cancer. ( 1 )

2 DOSAGE AND ADMINISTRATION ERLEADA 240 mg orally once daily. Swallow tablets whole. ERLEADA can be taken with or without food. ( 2.1 ) The recommended ERLEADA dosage in patients with severe hepatic impairment is 120 mg orally once daily. ( 2.3 ) Patients should also receive a gonadotropin-releasing hormone (GnRH) analog concurrently or should have had bilateral orchiectomy. ( 2.1 ) 2.1 Recommended Dosage The recommended dosage of ERLEADA is 240 mg orally once daily. ERLEADA can be taken with or without food [see Clinical Pharmacology (12.3) ] . Swallow the tablet(s) whole. Do not crush or split tablet(s). Patients should also receive a gonadotropin-releasing hormone (GnRH) analog concurrently or should have had a bilateral orchiectomy. 2.2 Dosage Modifications for Adverse Reactions If Grade 3 or 4 adverse reactions, or other intolerable adverse reactions occur, withhold ERLEADA. Consider permanent discontinuation of ERLEADA for Grade 3 or 4 cerebrovascular and ischemic cardiovascular events [see Warnings and Precautions (5.1) ] . Permanently discontinue ERLEADA for severe ILD/pneumonitis or if no other potential causes of ILD/pneumonitis are identified, or confirmed SCARs, or for other Grade 4 skin reactions [see Warnings and Precautions (5.5 , 5.6) and Adverse Reactions (6.1) ] . For other adverse reactions, including those that may be related to increased exposure to ERLEADA due to drug interactions [see Drug Interactions (7.1) ] , resume ERLEADA at the same dose or at a reduced dose (180 mg or 120 mg) when symptoms improve to less than or equal to Grade 1 or original grade, if warranted. If the ERLEADA dose was reduced for an adverse reaction while receiving a drug that increases exposure to ERLEADA, consider resuming the previously tolerated dose after the drug has been discontinued for at least 3 half-lives. 2.3 Recommended Dosage in Patients with Severe Hepatic Impairment The recommended dosage of ERLEADA for patients with severe hepatic impairment (Child-Pugh Class C) is 120 mg orally once daily [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3) ] . 2.4 Alternate Methods of Administration Disperse Tablet(s) in Water and Administer with Orange Juice, Applesauce, or Additional Water For patients who cannot swallow tablets whole, the recommended dose of ERLEADA tablet(s) can be dispersed in non-carbonated water and then administered with either orange juice, applesauce, or additional water as follows: Place the entire prescribed dose of ERLEADA tablet(s) in a cup. Do not crush or split the tablet(s). For one 240 mg tablet: Add about 2 teaspoons (10 mL) of non-carbonated water to make sure that the tablet is completely immersed in water. For 60 mg tablets (prescribed dose of 240 mg, 180 mg, or 120 mg): Add about 4 teaspoons (20 mL) of non-carbonated water to make sure that the tablets are completely immersed in water. Wait 2 minutes until the tablet(s) are broken up and spread out, then stir the mixture. Add 2 tablespoons (30 mL) of either orange juice, applesauce, or additional water and stir the mixture. Swallow the mixture immediately. Rinse the cup with enough water to make sure the whole dose is taken and drink it immediately. Do not store ERLEADA that is mixed with non-carbonated water, orange juice, or applesauce for later use. Administer Tablet(s) Through a Feeding Tube ERLEADA tablet(s) can be administered through a feeding tube 8 French or greater as follows: For one 240 mg tablet: Place the tablet in the barrel of the syringe (use at least a 20 mL syringe) and draw up 10 mL of non-carbonated water into the syringe. For 60 mg tablets (prescribed dose of 240 mg, 180 mg, or 120 mg): Place the entire prescribed dose of ERLEADA tablets in the barrel of the syringe (use at least a 50 mL syringe) and draw up 20 mL of non-carbonated water into the syringe. Wait 10 minutes and then shake vigorously to disperse contents completely. Administer immediately through the feeding tube. Refill the syringe wi …

3 DOSAGE FORMS AND STRENGTHS Tablets: 240 mg: bluish grey to grey, oval, film-coated and debossed with "E240" on one side. 60 mg: slightly yellowish to greyish green, oblong, film-coated and debossed with "AR 60" on one side. Tablets: 240 mg ( 3 ) Tablets: 60 mg ( 3 )

4 CONTRAINDICATIONS None. ( 4 ) None.

6 ADVERSE REACTIONS The following are discussed in more detail in other sections of the labeling: Cerebrovascular and Ischemic Cardiovascular Events [see Warnings and Precautions (5.1) ] . Fractures [see Warnings and Precautions (5.2) ] . Falls [see Warnings and Precautions (5.3) ] . Seizure [see Warnings and Precautions (5.4) ] . Severe Cutaneous Adverse Reactions (SCARs) [see Warnings and Precautions (5.5) ] . Interstitial Lung Disease (ILD) [see Warnings and Precautions (5.6) ] . The most common adverse reactions (≥10%) are fatigue, arthralgia, rash, decreased appetite, fall, weight decreased, hypertension, hot flush, diarrhea, and fracture. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Janssen Products, LP at 1-800-526-7736 (1-800-JANSSEN) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The most common adverse reactions (≥ 10%) that occurred more frequently in the ERLEADA-treated patients (≥ 2% over placebo) from the randomized placebo-controlled clinical trials (TITAN and SPARTAN) were fatigue, arthralgia, rash, decreased appetite, fall, weight decreased, hypertension, hot flush, diarrhea, and fracture. Metastatic Castration-sensitive Prostate Cancer (mCSPC) TITAN, a randomized (1:1), double-blind, placebo-controlled, multi-center clinical study, enrolled patients who had mCSPC. In this study, patients received either ERLEADA at a dose of 240 mg daily or placebo. All patients in the TITAN study received a concomitant gonadotropin-releasing hormone (GnRH) analog or had prior bilateral orchiectomy. The median duration of exposure was 20 months (range: 0 to 34 months) in patients who received ERLEADA and 18 months (range: 0.1 to 34 months) in patients who received placebo. Ten patients (1.9%) who were treated with ERLEADA died from adverse reactions. The reasons for death were ischemic cardiovascular events (n=3), acute kidney injury (n=2), cardio-respiratory arrest (n=1), sudden cardiac death (n=1), respiratory failure (n=1), cerebrovascular accident (n=1), and large intestinal ulcer perforation (n=1). ERLEADA was discontinued due to adverse reactions in 8% of patients, most commonly from rash (2.3%). Adverse reactions leading to dose interruption or reduction of ERLEADA occurred in 23% of patients; the most frequent (>1%) were rash, fatigue, and hypertension. Serious adverse reactions occurred in 20% of ERLEADA-treated patients and 20% in patients receiving placebo. Table 1 shows adverse reactions occurring in ≥10% on the ERLEADA arm in TITAN that occurred with a ≥2% absolute increase in frequency compared to placebo. Table 2 shows laboratory abnormalities that occurred in ≥15% of patients, and more frequently (>5%) in the ERLEADA arm compared to placebo. Table 1: Adverse Reactions in TITAN (mCSPC) ERLEADA N=524 Placebo N=527 System/Organ Class Adverse reaction All Grades % Grade 3–4 % All Grades % Grade 3–4 % Musculoskeletal and connective tissue disorders Arthralgia Per the Common Terminology Criteria for Adverse Reactions (CTCAE), the highest severity for these events is Grade 3. 17 0.4 15 0.9 Skin and subcutaneous tissue disorders Rash Includes rash, rash maculo-papular, rash generalized, urticaria, rash pruritic, rash macular, conjunctivitis, erythema multiforme, rash papular, skin exfoliation, genital rash, rash erythematous, stomatitis, drug eruption, lichenoid eruption, mouth ulceration, rash pustular, blister, papule, pemphigoid, skin erosion, dermatitis, and rash vesicular. 28 6 9 0.6 Pruritus 11 0.2 4.6 0.2 Vascular disorders Hot flush 23 0 16 0 Hypertension 18 8 16 9 Additional adverse reactions of interest occurring in less than 10% of patients treated with ERLEADA included diarrhea (9% versus 6% on placebo), m …

7 DRUG INTERACTIONS Concomitant use with medications that are sensitive substrates of CYP3A4, CYP2C19, CYP2C9, UGT, P-gp, BCRP, or OATP1B1 may result in loss of activity of these medications. ( 7.2 ) 7.1 Effect of Other Drugs on ERLEADA Strong CYP2C8 or CYP3A4 Inhibitors Reduce the ERLEADA dose as recommended for adverse reactions [see Dosage and Administration (2.2) ] . Co-administration of a strong CYP2C8 or CYP3A4 inhibitor is predicted to increase the steady-state exposure of the active moieties (sum of unbound apalutamide plus the potency-adjusted unbound N-desmethyl-apalutamide). 7.2 Effect of ERLEADA on Other Drugs Substrates of CYP3A4, CYP2C9, CYP2C19, P-gp, BCRP, or OATP1B1 Refer to the Prescribing Information for these substrates. Consider alternative agents when possible or evaluate for loss of activity of the substrate if concomitant use cannot be avoided. Apalutamide is a strong inducer of CYP3A4 and CYP2C19, a weak inducer of CYP2C9, and an inducer of P-gp, BCRP, and OATP1B1. Apalutamide decreases exposure of substrates of CYP3A4, CYP2C19, CYP2C9, P-gp, BCRP, or OATP1B1 [see Clinical Pharmacology (12.3) ] , which may decrease the effectiveness of these substrates. 7.3 Laboratory Test Interference ERLEADA can interfere with certain digoxin immunoassays (e.g., Chemiluminescent Microparticle Immunoassays), resulting in falsely elevated digoxin plasma concentration results. Notify the laboratory conducting the digoxin plasma concentration assay to use an appropriate method in patients receiving ERLEADA and digoxin [see Warnings and Precautions (5.8) ] .

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary The safety and efficacy of ERLEADA have not been established in females. Based on findings from animals and its mechanism of action, ERLEADA can cause fetal harm and loss of pregnancy when administered to a pregnant female [see Clinical Pharmacology (12.1) ] . There are no available data on ERLEADA use in pregnant women to inform a drug-associated risk. In an animal reproduction study, oral administration of apalutamide to pregnant rats during and after organogenesis resulted in fetal abnormalities and embryo-fetal lethality at maternal exposures ≥ 2 times the human clinical exposure (AUC) at the recommended dose (see Data ) . Data Animal Data In a pilot embryo-fetal developmental toxicity study in rats, apalutamide caused developmental toxicity when administered at oral doses of 25, 50 or 100 mg/kg/day throughout and after the period of organogenesis (gestational days 6–20). Findings included embryo-fetal lethality (resorptions) at doses ≥50 mg/kg/day, decreased fetal anogenital distance, misshapen pituitary gland, and skeletal variations (unossified phalanges, supernumerary short thoracolumbar rib(s), and small, incomplete ossification, and/or misshapen hyoid bone) at ≥25 mg/kg/day. A dose of 100 mg/kg/day caused maternal toxicity. The doses tested in rats resulted in systemic exposures (AUC) approximately 2, 4 and 6 times, respectively, the AUC in patients. 8.2 Lactation Risk Summary The safety and efficacy of ERLEADA have not been established in females. There are no data on the presence of apalutamide or its metabolites in human milk, the effect on the breastfed child, or the effect on milk production. 8.3 Females and Males of Reproductive Potential Contraception Males Based on the mechanism of action and findings in an animal reproduction study, advise male patients with female partners of reproductive potential to use effective contraception during treatment and for 3 months after the last dose of ERLEADA [see Use in Specific Populations (8.1) ] . Infertility Males Based on animal studies, ERLEADA may impair fertility in males of reproductive potential [see Nonclinical Toxicology (13.1) ] . 8.4 Pediatric Use Safety and effectiveness of ERLEADA in pediatric patients have not been established. 8.5 Geriatric Use Of the 1327 patients who received ERLEADA in clinical studies, 19% of patients were less than 65 years, 41% of patients were 65 years to 74 years, and 40% were 75 years and over. No overall differences in effectiveness were observed between older and younger patients. Of patients treated with ERLEADA (n=1073), Grade 3–4 adverse reactions occurred in 39% of patients younger than 65 years, 41% of patients 65–74 years, and 49% of patients 75 years or older. Falls in patients receiving ERLEADA with androgen deprivation therapy was elevated in the elderly, occurring in 8% of patients younger than 65 years, 10% of patients 65–74 years, and 19% of patients 75 years or older. 8.6 Hepatic Impairment The recommended ERLEADA dosage in patients with severe hepatic impairment (Child-Pugh C) is lower than the recommended dosage in patients with normal hepatic function [see Dosage and Administration (2.3) ] . No dosage modification is recommended for patients with mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic impairment [see Clinical Pharmacology (12.3) ] .

12.1 Mechanism of Action Apalutamide is an Androgen Receptor (AR) inhibitor that binds directly to the ligand-binding domain of the AR. Apalutamide inhibits AR nuclear translocation, inhibits DNA binding, and impedes AR-mediated transcription. A major metabolite, N-desmethyl apalutamide, is a less potent inhibitor of AR, and exhibited one-third the activity of apalutamide in an in vitro transcriptional reporter assay. Apalutamide administration caused decreased tumor cell proliferation and increased apoptosis leading to decreased tumor volume in mouse xenograft models of prostate cancer.

11 DESCRIPTION Apalutamide, the active ingredient of ERLEADA, is an androgen receptor inhibitor. Each ERLEADA tablet contains either 60 mg or 240 mg of apalutamide. The chemical name is (4-[7-(6-Cyano-5-trifluoromethylpyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]oct-5-yl]-2-fluoro-N-methylbenzamide). Apalutamide is a white to slightly yellow powder. Apalutamide is practically insoluble in aqueous media over a wide range of pH values. The molecular weight is 477.44 and molecular formula is C 21 H 15 F 4 N 5 O 2 S. The structural formula is: ERLEADA ® (apalutamide) tablets are available in 240 mg tablets and 60 mg tablets with the following inactive ingredients: 240 mg film-coated tablets: colloidal anhydrous silica, croscarmellose sodium, hydroxypropyl methylcellulose-acetate succinate, silicified microcrystalline cellulose, and magnesium stearate. The coating contains glyceryl monocaprylocaprate, iron oxide black, polyvinyl alcohol, talc, titanium dioxide, and vinyl alcohol grafted copolymer. 60 mg film-coated tablets: colloidal anhydrous silica, croscarmellose sodium, hydroxypropyl methylcellulose-acetate succinate, magnesium stearate, microcrystalline cellulose, and silicified microcrystalline cellulose. The coating contains iron oxide black, iron oxide yellow, polyethylene glycol, polyvinyl alcohol, talc, and titanium dioxide. Chemical Structure

10 OVERDOSAGE There is no known specific antidote for apalutamide overdose. In the event of an overdose, stop ERLEADA, undertake general supportive measures until clinical toxicity has been diminished or resolved.

16 HOW SUPPLIED/STORAGE AND HANDLING ERLEADA ® (apalutamide) tablets are available in the strengths and packages listed below: ERLEADA ® 240 mg Tablets Film coated, bluish grey to grey, oval-shaped tablets debossed with "E240" on one side. NDC Number 59676‐604‐30 - 30 tablets available in bottles with a silica gel desiccant and has a child-resistant closure ERLEADA ® 60 mg Tablets Film coated, slightly yellowish to greyish green, oblong-shaped tablets debossed with "AR 60" on one side. NDC Number 59676‐600‐12 - 120 tablets available in bottles with a silica gel desiccant and has a child-resistant closure Storage and Handling Store at 20 °C to 25 °C (68 °F to 77 °F); excursions permitted to 15 °C to 30 °C (59 °F to 86 °F) [see USP Controlled Room Temperature] . Store in original package to protect from light and moisture. Do not discard desiccant.