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ERLEADA®

(apalutamide)

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ERLEADA® (apalutamide)

Medical Information

ERLEADA - Severe Cutaneous Adverse Reactions (SCARs)

Last Updated: 12/17/2025

SUMMARY  

  • Rare postmarketing cases of severe cutaneous adverse reactions (SCARs) including drug reaction with eosinophilia and systemic symptoms (DRESS) and Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), which can be life-threatening or may lead to death, have been reported with ERLEADA. Discontinue ERLEADA immediately if signs or symptoms of a SCAR develop.1 Please refer to local labeling for additional considerations and data.
    • DRESS frequency was 11 cases/48,249 person-years or 2.3 cases/10,000 personyears (through 25 Feb 2022). These cases were reported in France, Japan, Singapore, Belgium, China, and Switzerland.2
      • Of the 11 cases, 2 cases were considered as potentially representative of DRESS with causality assessed as possibly related to ERLEADA.
    • SJS/TEN frequency was 30 cases/38,906 person-years or 7.71 cases/10,000 personyears (through 15 Oct 2021). These cases were reported globally (including 4 in the US) with 19 cases from Japan.3
  • There were no events of DRESS, SJS, or TEN reported with ERLEADA in the phase 3, randomized, placebo-controlled, registrational TITAN (N=1052) and SPARTAN (N=1207) studies in patients with metastatic castration-sensitive prostate cancer (mCSPC) and nonmetastatic castration-resistant prostate cancer (nmCRPC), respectively.4-6
  • In the phase 2 APA-RP study in treatment-naïve patients with high-risk localized prostate cancer who had undergone radical prostatectomy (N=108), SJS was reported as a treatment-emergent serious adverse event (AE) in 1 patient (0.9%) receiving ERLEADA plus androgen deprivation therapy (ADT).7
  • Published case reports and retrospective studies related to SCARs in patients receiving ERLEADA were identified in the literature.8-25
  • SCARs have been reported with ERLEADA use based on real-world postmarketing data from select regulatory agency databases.15,26-29
  • A review article was additionally identified to assess characteristics of mild and severe ERLEADA-related cutaneous AEs per onset time and lymphocyte transformation test results in patients with prostate cancer.30

POSTMARKETING SAFETY

Case Reports and Retrospective Studies

Published case reports were identified in the literature for ERLEADA and SCARs, including fatal cases.8-22 SCAR types included SJS, TEN, DRESS, acute generalized exanthematous pustulosis (AGEP), and/or generalized bullous fixed drug eruptions (GBFDE). Dosage regimen, onset, concomitant medications, clinical characteristics, intervention/management, and/or outcomes are reported in the respective publications.

Three retrospective studies in Japan reported ERLEADA-associated SCARs in patients with prostate cancer: one grade 5 TEN event, one case of AGEP, and one fatal case of TEN-related multiple organ failure.23-25

Postmarketing Safety Databases

SCARs have been reported with ERLEADA use based on published real-world postmarketing data from the United States Food and Drug Administration Adverse Event Reporting System (FAERS). Disproportionality analyses were used to identify AE signals in reports where ERLEADA was documented as primary or secondary suspect from the first quarter of 2018 to the first quarter of 2022. Preferred Terms (PTs) by the Medical Dictionary for Regulatory Activities (MedDRA) and reporting odds ratio (ROR) were used for identifying signals indicating a potentially increased risk of drug-associated AEs. Of 4156 total AE reports, 24 AEs of TEN (ROR of 14.46 [95% CI, 9.68-21.60]), 17 AEs of DRESS (ROR of 4.55 [95% CI, 2.82-7.32]), 11 AEs of SJS (ROR of 5.66 [95% CI, 3.13-10.24]), and 5 AEs of AGEP (ROR of 5.06 [95% CI, 2.10-12.16]) were reported.15

SCARs were reported with ERLEADA use based on postmarketing data from an observational retrospective pharmacovigilance study using FAERS/EudraVigilance/Japanese Adverse Drug Event Report (JADER) databases. Significant over-reporting signals for ERLEADA were observed in SJS, TEN, DRESS, and AGEP. The lethal rates of ERLEADA-related SCARs were 24.4% for SJS, 51.1% for TEN, and 11.8% for DRESS. The median time to onset was 41 days for SJS, 29 days for TEN, and 40 days for DRESS.27

  • SJS: 30 cases in FAERS (ROR025 of 4.12, information component [IC025] of 1.70), 55 cases in EudraVigilance (ROR025 of 11.54, IC025 of 2.84), 25 cases in JADER (ROR025 of 2.90, IC025 of 1.33)
  • TEN: 29 cases in FAERS (ROR025 of 4.40, IC025 of 1.75), 58 cases in EudraVigilance (ROR025 of 30.96, IC025 of 3.74), 25 cases in JADER (ROR025 of 5.34, IC025 of 1.85)
  • DRESS: 38 cases in FAERS (ROR025 of 2.68, IC025 of 1.33), 55 cases in EudraVigilance (ROR025 of 25.06, IC025 of 3.53), 6 cases in JADER (ROR025 of 0.62, IC025 of 0.19)
  • AGEP: 7 cases in FAERS (ROR025 of 1.16, IC025 of 0.55), 5 cases in EudraVigilance (ROR025 of 4.18, IC025 of 1.02), 4 cases in JADER (ROR025 of 1.05, IC025 of 0.45)

SCARs were reported with ERLEADA use in a retrospective disproportionality study, using ROR with IC based on postmarketing FAERS data. The median time to onset of all skin AEs was 55 days.28

  • DRESS: 32 cases (ROR of 4.59 [95% CI, 3.24-6.49], IC of 2.19 [IC025, 0.53])
  • SJS: 29 cases (ROR of 8.41 [95% CI, 5.83-12.11], IC of 3.06 [IC025, 1.40])
  • TEN: 28 cases (ROR of 9.02 [95% CI, 6.22-13.09], IC of 3.17 [IC025, 1.50])

SCARs were reported with ERLEADA use in a pharmacovigilance study using 4 disproportionality analysis algorithms, including ROR, proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS) based on the FAERS data. The median time to onset for ERLEADA-associated SCARs was 30 days. The disproportionality analysis revealed ROR of 33.32 (95% CI, 23.37-47.49), PRR of 33.04 (χ²,953.71), IC025 of 3.64, and empirical Bayesian geometric mean (EBGM05) of 9.66 for ERLEADA-associated SCARs.29

In a published analysis of SJS and TEN data in the Russian National Pharmacovigilance database of spontaneous events from April 2019-December 2023, 1 (2.1%) elderly patient receiving ERLEADA had SJS/TEN.26

Literature Search

A literature search of MEDLINE®, Embase®, BIOSIS Previews®, and Derwent Drug File (and/or other resources, including internal/external databases) was conducted on 25 September 2025.

References

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1 Data on File. Apalutamide. Company Core Data Sheet. Janssen Research & Development, LLC. EDMS-ERI-146013831; 2025.  
2 Data on File. Apalutamide. Cumulative Review. Janssen Research & Development, LLC. EDMS-RIM-698816; 2022.  
3 Data on File. Apalutamide. CCDS Update. Janssen Research & Development, LLC. EDMS-RIM-657332; 2022.  
4 Chi KN, Chowdhury S, Bjartell A, et al. Apalutamide in patients with metastatic castration-sensitive prostate cancer: final survival analysis of the randomized, double-blind, phase III TITAN study. J Clin Oncol. 2021;39(20):2294-2303.  
5 Smith MR, Saad F, Chowdhury S, et al. Supplement for: Apalutamide treatment and metastasis-free survival in prostate cancer. N Engl J Med. 2018;378(15):1408-1418.  
6 Data on File. TITAN Clinical Study Report. Janssen Research & Development, LLC. EDMS-ERI-174221283; 2019.  
7 Shore N, Hafron J, Saltzstein D, et al. Apalutamide for high-risk localized prostate cancer following radical prostatectomy (Apa-RP). J Urol. 2024;212(5):682-691.  
8 Ducharme O, Sanchez‐Pena P, Pham‐Ledard A, et al. The first case of drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome caused by apalutamide, a novel oral androgen receptor antagonist. Contact Dermatitis. 2022;86(4):313-315.  
9 Hsu YO, Hsieh T, Huang P, et al. Drug reaction with eosinophilia and systemic symptoms with features resembling Stevens–Johnson syndrome/toxic epidermal necrolysis related to apalutamide. J Eur Acad Dermatol Venereol. 2023;37(2):e246-e248.  
10 Osawa K, Kiniwa Y, Shimosato Y, et al. Toxic epidermal necrolysis caused by apalutamide: a case report of treatment using etanercept with conventional steroid therapy. Acta Derm Venereol. 2022;102:adv00723.  
11 Miyagawa A, Adachi T, Kobayashi Y, et al. Plasmapheresis as a promising treatment option in apalutamide‐associated toxic epidermal necrolysis. J Dermatol. 2022;49(3):e102-e103.  
12 Sagawa N, Watanabe Y, Mizuno Y, et al. A case of toxic epidermal necrolysis associated with apalutamide administration [letter to the editor]. Journal of Cutaneous Immunology and Allergy. 2020;3(6):134-135.  
13 Endo Y, Oka A, Uehara A, et al. Fatal case of toxic epidermal necrolysis due to apalutamide used as a novel prostate cancer drug. J Dermatol. 2020;47(10):e359-e360.  
14 Honda T, Tohi Y, Kaku Y, et al. Acute generalized exanthematous pustulosis during apalutamide treatment in a patient with prostate cancer. IJU Case Rep. 2022;5(6):497-500.  
15 Fang Z, Xu Z, Zhu W, et al. A real-world disproportionality analysis of apalutamide: data mining of the FDA adverse event reporting system. Front Pharmacol. 2023;14:1101861.  
16 Martin G, Lambert E, Wang GK. Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome caused by apalutamide: a case presentation. Cureus. 2023;15(7):e41687.  
17 Flynn CR, Liu SC, Byrne B, et al. Apalutamide-induced toxic epidermal necrolysis in a Caucasian patient with metastatic castration-sensitive prostate cancer: a case report and review of the literature. Case Rep Oncol. 2023;16(1):646-655.  
18 Wu W, Da M, Chen M, et al. Toxic epidermal necrolysis post apalutamide with preceding tislelizumab administration in a patient with two cancers. J Dtsch Dermatol Ges. 2023;21(10):1221-1223.  
19 Wang Q, Cao H, Zhang X, et al. Case report: apalutamide-induced severe lethal cutaneous adverse effects in China. Front Immunol. 2024. doi:10.3389/fimmu.2023.1291564.  
20 Hallamies S, Auvinen R, Junkkari H, et al. Cutaneous adverse reactions associated to apalutamide: two case reports of DRESS syndrome and maculopapular exanthema. Scand J Urol. 2024;59:119-120.  
21 Akai N, Hashimoto T, Okuno S, et al. Apalutamide‐induced drug‐induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms involving reactivation of human herpesvirus‐6 and cytomegalovirus: a case report. J Dermatol. 2025;52(7):e658-e660.  
22 Tanaka Y, Fujimura Y, Morishita K, et al. A case of drug‐induced hypersensitivity syndrome caused by apalutamide. IJU Case Rep. 2025;8(5):529-532.  
23 Tohi Y, Kato T, Fukuhara H, et al. Real-world analysis of apalutamide-associated skin adverse events in Japanese patients with advanced prostate cancer: a multi-institutional study in the Chu-shikoku Japan Urological Consortium. Int J Clin Oncol. 2022;27(8):1348-1355.  
24 Sakai Y, Nagamine Y, Yokose M, et al. Clinical features and prognosis of toxic epidermal necrolysis requiring intensive care: a retrospective descriptive single-center study. Burn Open. 2023;7(4):139-145.  
25 Sasaki D, Hatakeyama S, Tanaka T, et al. Impact of body size on skin‐related adverse events in advanced prostate cancer treated with apalutamide: a multicenter retrospective study. Int J Urol. 2022;29(7):772-773.  
26 Zyryanov S, Asetskaya I, Butranova O, et al. Stevens-Johnson syndrome and toxic epidermal necrolysis: analysis of the Russian database of spontaneous reports. Pharmaceuticals. 2024;17(6).  
27 Zhu J, Huo X, Li X, et al. Severe cutaneous adverse reactions associated with novel antiandrogens: a disproportionality analysis of three databases. Int J Cancer. 2025;157(12):2589-2602.  
28 Chen Y, Huang L, Li W, et al. Exploring skin adverse events and mechanisms of apalutamide using data mining algorithms and network pharmacology. Front Pharmacol. 2025;16:1517874.  
29 Liu J, Liu X, Zeng H, et al. Severe cutaneous adverse reactions associated with second-generation androgen receptor antagonists in prostate cancer patients. PLOS One. 2025;20(6):e0325448.  
30 Katsuta M, Nobeyama Y, Hirafuku K, et al. Characteristics of mild and severe apalutamide‐related cutaneous adverse events in patients with prostate cancer: a review of the literature. J Dermatol. 2024;51(1):110-114.