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ERLEADA® (apalutamide)
Medical Information
ERLEADA - Use of ERLEADA in Patients with Hepatic Impairment
Last Updated: 04/13/2026
SUMMARY
- The recommended dosage of ERLEADA for patients with severe hepatic impairment (Child-Pugh Class C) is 120 mg (two 60 mg tablets) administered orally once daily.1
Please refer to local labeling for additional considerations and data. - No dosage modification is recommended for patients with mild (Child-Pugh Class A) or moderate (Child-Pugh Class B) hepatic impairment.1
- In the phase 3 SPARTAN Study and TITAN Study, eligible patients were required to have adequate hepatic function (defined as serum aspartate transaminase [AST] and serum alanine transaminase [ALT] ≤2.5x upper limit of normal [ULN], and total serum bilirubin ≤1.5x ULN).2
- 5 - A phase 1, open‑label, multicenter, non‑randomized study (NCT02170220) evaluated the pharmacokinetics (PK) and safety of ERLEADA following single oral doses of 120 mg and 240 mg in participants with severe hepatic impairment (SHI; Child-Pugh Class C) and normal hepatic function (NHF), respectively.6
- In participants with SHI, overall exposure of the active moieties (sum of unbound apalutamide plus potency-adjusted unbound N-desmethyl apalutamide) with the reduced 120 mg dose was comparable to that observed with the standard 240 mg dose in participants with NHF.
- Overall, 4 (22.2%) participants reported ≥1 treatment-emergent adverse event (TEAE), none of which were considered related to the study drug. No TEAEs were reported in participants with NHF. No TEAEs led to study discontinuation other than a death due to bacterial sepsis, which was not considered related to the study drug.
clinical DATA
In the phase 3 SPARTAN study, which evaluated the efficacy and safety of ERLEADA compared to placebo in patients with high-risk non-metastatic castration-resistant prostate cancer (nmCRPC; defined as prostate-specific antigen [PSA] doubling time [PSADT]
≤10 months) on continuous androgen deprivation therapy (N=1207), eligible patients were required to have adequate hepatic function, which was defined by the following criteria: serum AST and serum ALT ≤2.5x ULN, and total serum bilirubin ≤1.5x ULN.2,
In the phase 3 TITAN study, which evaluated the efficacy and safety of ERLEADA compared to placebo in patients with metastatic castration-sensitive prostate cancer (mCSPC) on continuous ADT (N=1052), eligible patients were required to have adequate hepatic function, which was defined by the following criteria: serum AST and serum ALT ≤2.5x ULN, and total serum bilirubin ≤1.5x ULN.4
Phase 1 Study
A phase 1 study evaluated the PK and safety of ERLEADA following single oral doses of 120 mg and 240 mg in participants with SHI (Child-Pugh Class C) and NHF, respectively (N=18).6
Study Design/Methods
- Phase 1, open‑label, multicenter, non‑randomized study.
- All participants were administered a single oral dose of ERLEADA on day 1 under fasting conditions.
- Blood samples were collected to quantify plasma concentrations of apalutamide and its primary active metabolite, N-desmethyl apalutamide.
- Plasma protein binding was evaluated pre- and post-dose to determine the unbound fraction (Fu) and geometric mean ratios (GMR) were calculated to compare both groups.
Results
Baseline Characteristics
Demographics and baseline characteristics are summarized in Table: Baseline Demographics. Among the 10 participants with SHI, 8 completed the study and 2 discontinued the study prematurely.
| Characteristic | SHI (n=10) | NHF (n=8) | Total (N=18) |
|---|---|---|---|
| Age, median (range), years | 54 (38-69) | 54.5 (44-63) | 54 (38-69) |
| Race, n (%) | |||
| Black or African American | 0 | 2 (25) | 2 (11.1) |
| White | 10 (100) | 6 (75) | 16 (88.9) |
| Ethnicity, n (%) | |||
| Hispanic or Latino | 9 (90) | 8 (100) | 17 (94.4) |
| Not Hispanic or Latino | 1 (10) | 0 | 1 (5.6) |
| Weight, median (range), kg | 85.9 (50.3-99) | 82.1 (72-94.9) | 84.65 (50.3-99) |
| Height, median (range), cm | 171.3 (155-179.8) | 171 (159-189) | 171.05 (155-189) |
| BMI, median (range), kg/m2 | 29.57 (20.7-32.2) | 27.85 (24.3-31.8) | 29.14 (20.7-32.2) |
| Child-Pugh score, median (range) | 10.5 (10-13) | - | 10.5 (10-13) |
| Abbreviations: BMI, body mass index; NHF, normal hepatic function; SHI, severe hepatic impairment. | |||
PK
- In participants with SHI, overall exposure of the active moieties (sum of unbound apalutamide plus potency-adjusted unbound N-desmethyl apalutamide) with the reduced 120 mg dose was comparable to that observed with the standard 240 mg dose in participants with NHF.
- PK data for total and unbound apalutamide are summarized in Table: Plasma PK Parameters of Total and Unbound Apalutamide and N-desmethyl Apalutamide and Table: Exposure of Total and Unbound Apalutamide and N-desmethyl Apalutamide.
| PK Parameter | Apalutamide | N-desmethyl apalutamidea | ||||
|---|---|---|---|---|---|---|
| N | SHI | NHF | N | SHI | NHF | |
| tmax, h | 10/8 | 2.5 (1-48) | 3 (2-6) | 9/8 | 240 (96-504) | 228 (168-336) |
| CL/F, L/h | 9/8 | 0.922 (0.163) | 1.32 (0.211) | - | - | - |
| CLunb/F, L/h | 9/8 | 16.4 (8.78) | 31 (5.02) | - | - | - |
| Vd/F, L | 9/8 | 388 (125) | 413 (119) | - | - | - |
| t1/2, h | 9/8 | 293.4 (89.4) | 221.8 (69.4) | 6/7 | 367.4 (146.6) | 263.6 (78.3) |
| Fub | 10/8 | 0.067 (0.0239) | 0.0429 (0.00547) | 9/8 | 0.0656 (0.0197) | 0.0403 (0.00549) |
| MPR Cmax, % | - | - | - | 9/8 | 19.47 (10.08) | 20.56 (4.69) |
| MPR AUClast, % | - | - | - | 7/8 | 68.2 (26.82) | 98.56 (23.92) |
| MPR AUC∞, % | - | - | - | 6/7 | 71.54 (30.42) | 103.41 (24.37) |
| Abbreviations: AUClast, area under the curve to the last measurable concentration; AUC∞, area under the curve from time zero to infinity; Cmax, maximum plasma concentration; CL/F, apparent oral clearance defined as the ratio of clearance to the fraction of dose absorbed; Fu, unbound fraction; h, hour; L, liter; NHF, normal hepatic function; MPR, medication possession ratio; PK, pharmacokinetic; SD, standard deviation; SHI, severe hepatic impairment; tmax, time to maximum concentration; t1/2, elimination half-life; tlast, time of last quantifiable concentration; unb, unbound; Vd/F, apparent volume of distribution divided by bioavailability.aActive metabolite of apalutamide.bThe Fu at 3 hours was used for apalutamide and at 216 hours for N-desmethyl apalutamide. Note: Data shown as mean (SD), tmax and tlast shown as median (range); N=SHI/NHF. | ||||||
| PK Parameter | N | Geometric Mean | GMR, % | 90% CI | CV, % | |
|---|---|---|---|---|---|---|
| NHF (ref) | SHI (test) | |||||
| Apalutamide | ||||||
| Cmax | 8/10 | 1.34 | 0.706 | 52.54 | 38.32-72.04 | 39.5 |
| AUClast | 8/7 | 179 | 126 | 70.27 | 61.97-79.68 | 13.8 |
| AUC∞ | 8/9 | 184 | 132 | 71.8 | 61.97-83.18 | 17.4 |
| Cmax unba | 8/10 | 0.0573 | 0.0445 | 77.76 | 51.29-117.89 | 53.6 |
| AUClast unba | 8/7 | 7.62 | 8.63 | 113.25 | 87.79-146.09 | 28.3 |
| AUC∞ unba | 8/9 | 7.84 | 8.11 | 103.37 | 76.07-140.48 | 37.2 |
| N-desmethyl apalutamideb | ||||||
| Cmax | 8/9 | 0.262 | 0.116 | 44.07 | 29.56-65.7 | 49.6 |
| AUClast | 8/7 | 167 | 76 | 45.49 | 33.81-61.21 | 33.2 |
| AUC∞ | 7/6 | 182 | 87.1 | 47.82 | 34.35-66.55 | 34 |
| Cmax unbc | 8/8 | 0.0105 | 0.00655 | 62.47 | 38.39-101.64 | 59.8 |
| AUClast unbc | 8/7 | 6.67 | 4.9 | 73.42 | 50.71-106.31 | 42.1 |
| AUC∞ unbc | 7/5 | 7.03 | 4.84 | 68.83 | 44.89-105.55 | 42 |
| Abbreviations: AUClast, area under the curve to the last measurable concentration; AUC∞, area under the curve from time zero to infinity; Cmax, maximum plasma concentration; CI, confidence interval; CV, coefficient of variation; Fu, unbound fraction; GMR, geometric mean ratio; N, number of observations (NHF/SHI); NHF, normal hepatic function; PK, pharmacokinetic; SHI, severe hepatic impairment; unb, unbound. aThe Fu at 3 hours was used to calculate.bActive metabolite of apalutamide.cThe Fu at 216 hours was used to calculate.Note: Cmax (μg/mL), AUClast (μg*h/mL), and AUC∞ (μg*h/mL) for both total and unbound analytes. | ||||||
Safety
- Overall, 4 (22.2%) participants reported ≥1 TEAE, none of which were considered related to the study drug. No TEAEs were reported in participants with NHF.
- Among participants with SHI, 1 (10%) experienced grade 1 TEAEs, including neutrophilia and fall, neither considered related to the study drug per investigator; 3 (30%) experienced grade 2 TEAEs, including eye injury and hand fracture (n=1), Klebsiella urinary tract infection and hematuria (n=1), and worsening encephalopathy (n=1), all unrelated to the study drug; 1 (10%) experienced grade 3 TEAEs, including hepatic cirrhosis, bacterial peritonitis, and esophageal varices hemorrhage, all considered related to the participant’s medical history of hepatic cirrhosis.
- One (10%) participant died due to a serious TEAE of bacterial sepsis, which was not considered related to the study drug. No TEAEs led to study discontinuation other than the death due to bacterial sepsis.
- No clinically significant or study drug-related effects were observed on laboratory safety parameters, vital signs, or electrocardiograms.
Literature Search
A literature search of MEDLINE®
References
| 1 | Data on File. Apalutamide. Company Core Data Sheet. Janssen Research & Development, LLC. EDMS-ERI-146013831; 2026. |
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