ZYTIGA - Drug Interactions

SUMMARY

• Following oral administration, abiraterone acetate (AA) is hydrolyzed to the active metabolite, abiraterone, likely through esterase activity.¹
• Based on in vitro data, abiraterone is a substrate of CYP3A4. Strong inducers of CYP3A4 (eg, phenytoin, carbamazepine, rifampicin, rifabutin, rifapentine, phenobarbital) during treatment with ZYTIGA are to be avoided or used with careful evaluation of clinical efficacy.^2,3 Please refer to the product labeling for additional information.
• AA is an inhibitor of CYP2D6 and CYP2C8. Avoid coadministration of ZYTIGA with substrates of CYP2D6 with a narrow therapeutic index. If alternative treatments cannot be used, exercise caution and consider a dose reduction of the concomitant CYP2D6 substrate drug.⁴ Clinicians should consider the therapeutic index of CYP2C8 substrate drugs when used concomitantly with ZYTIGA.⁵
• Dai et al (2026)⁶ conducted a phase 1 dose-escalation and expansion trial to evaluate the pharmacokinetics (PK), efficacy, and safety of fuzuloparib in combination with ZYTIGA and prednisone for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) who had not previously received novel androgen receptor-targeted therapy (N=39). No obvious drug-drug interaction was observed between ZYTIGA and fuzuloparib.
• Chandran et al (2026)⁷ conducted a phase 1 trial to assess the safety, tolerability, and antitumor activity of tildrakizumab in combination with AA in men with endocrine treatment-resistant mCRPC (N=13) with progression after ≥1 androgen receptor pathway inhibitor (ARPI). PK sampling data indicated no evidence of a drug-drug interaction between AA and tildrakizumab.
• Smoragiewicz et al (2026)⁸ conducted a phase 1b trial to evaluate the safety, PK, and preliminary antitumor activity of bavdegalutamide in combination with ZYTIGA and a concomitant corticosteroid in adult male patients with metastatic prostate cancer and increasing prostate-specific antigen (PSA) levels on ZYTIGA therapy (N=45; NCT05177042). No clinically significant effects of bavdegalutamide were observed on the PK of ZYTIGA.
• Taha et al (2025)⁹ presented a single-patient chart review of a 76-year-old male patient with a history of chronic kidney disease, diabetes, hyperlipidemia, and stage IIIc prostate cancer who developed severe rhabdomyolysis after concomitant treatment with ZYTIGA and rosuvastatin. His condition improved following discontinuation of ZYTIGA and rosuvastatin.
• Additional relevant citations identified in the published literature are cited here.^10,11

DRUG INTERACTIONS

For up-to-date drug interaction, pharmacokinetic, and pharmacodynamic clinical data pertaining to specific medicinal agents, please review the local labeling of ZYTIGA and/or contact the manufacturers of these agents for additional information.

CLINICAL STUDIES

Phase 1 Studies

Dai et al (2026)⁶ presented results from a phase 1 dose-escalation and expansion trial to evaluate the PK, efficacy, and safety of fuzuloparib in combination with ZYTIGA and prednisone for the treatment of patients with mCRPC who had not previously received novel androgen receptor-targeted therapy (N=39). During the dose-escalation phase, patients received fuzuloparib 100 or 150 mg twice daily (BID) for 5 days, followed by fuzuloparib plus ZYTIGA 1000 mg once daily (QD) and prednisone 5 mg BID in 28-day treatment cycles. The higher tolerated dose of fuzuloparib was selected for the dose-expansion phase. In this phase, patients in the fuzuloparib group received fuzuloparib for 5 days, whereas those in the ZYTIGA group received ZYTIGA and prednisone for 5 days. Subsequently, both groups were treated with combination therapy until disease progression or unacceptable toxicity. No obvious drug-drug interaction was observed between ZYTIGA and fuzuloparib.

Chandran et al (2026)⁷ conducted a phase 1 trial to assess the safety, tolerability, and antitumor activity of tildrakizumab in combination with AA in men with endocrine
treatment-resistant mCRPC (N=13) with progression after ≥1 ARPI. Of the 13 patients, 9 had sufficient PK sampling performed to enable PK profiling. Patients were administered escalating doses of tildrakizumab (100 mg, 300 mg, 600 mg every 4 weeks [Q4W]) and AA (500 mg oral QD) to establish the recommended phase 2 dose. PK samples for AA were collected at the start of the run-in period and predose on cycle 1 day 1 and cycle 2 day 1. The PK sampling data showed drug levels to be comparable with historical data for the same formulation, with no significant change in drug levels (maximum serum concentration [C_max] and area under the curve from time 0 to the last measurable point [AUC_last]) before and after tildrakizumab commencement, indicating lack of any drug-drug interaction between AA and tildrakizumab.

Smoragiewicz et al (2026)⁸ conducted an open-label, multicenter, nonrandomized phase 1b trial to evaluate the safety, PK, and preliminary antitumor activity of bavdegalutamide in combination with ZYTIGA and a concomitant corticosteroid in adult male patients with metastatic prostate cancer and increasing PSA levels on ZYTIGA therapy (N=45; NCT05177042). PK parameters for ZYTIGA, administered with or without bavdegalutamide, were assessed in 6 patients. Changes in PK parameters (including C_max, AUC_last, and area under the concentration-time curve until the end of the dosing interval [AUC_tau]) for ZYTIGA alone (as measured on day -1) compared with those for ZYTIGA plus bavdegalutamide (as measured on cycle 1 day 21) were not clinically significant.

Case Report

Taha et al (2025)⁹ presented a single-patient chart review of a 76-year-old male patient with a history of chronic kidney disease, diabetes, hyperlipidemia, and stage IIIc prostate cancer. He presented to the emergency department with bilateral thigh pain that was refractory to over-the-counter analgesics. Four months earlier, he had initiated treatment with ZYTIGA plus prednisone and had been receiving rosuvastatin for several years. The patient had severe rhabdomyolysis (creatine phosphokinase [CK]=32,454 IU/L; upper limit of normal=294 IU/L) and acute kidney injury (creatinine=2.9 mg/dL). His treatment consisted of normal saline infusion at 200 mL/h and discontinuation of ZYTIGA, prednisone, and rosuvastatin. His creatinine levels returned to baseline over the course of a 4-day admission, and his CK levels improved to 14,000 IU/L before discharge, further improving to <1000 IU/L at the 2-week outpatient follow-up.

Literature Search

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File (and/or other resources, including internal/external databases) pertaining to this topic was conducted on 27 July 2026.