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PARP inhibitor

Talazoparib

Talzenna · Tala

PARP inhibitor · approved 2018 · 6 references

A potent, renally cleared PARP-trapper — renal impairment raises exposure and dosing must adjust.

Signature injury
Pseudo-AKI
Severity
Mild
Reversibility
Reversible
Onset
The pharmacokinetic effect is present from initiation in patients with reduced renal function; cytopenias accrue over the first cycles.

Signature kidney injury & incidence

Pseudo-AKI.

Renal clearance is a major elimination route (~two-thirds of dose), so exposure rises with declining renal function: dedicated PK studies show higher AUC and more myelosuppression in moderate-severe impairment, mandating dose reduction. Class-level mild creatinine elevation may occur; severe intrinsic nephrotoxicity is uncommon.

Source: Durairaj et al., Clin Pharmacokinet 2021

Reported injury signatures: Pseudo-AKI.

Onset timing & rechallenge

Hyperacute (<24 h) — The pharmacokinetic effect is present from initiation in patients with reduced renal function, while cytopenias accrue over the first cycles.

Mechanism of kidney injury

Talazoparib is substantially renally cleared, so reduced GFR increases drug exposure (and hematologic toxicity) rather than causing direct tubular injury — the dominant renal issue is pharmacokinetic. As with the class, any modest creatinine rise can reflect inhibition of tubular creatinine secretion rather than true filtration loss.

Clinical presentation

Usually no overt nephrotoxicity; the renal concern is pharmacokinetic — higher exposure with anemia, thrombocytopenia, and neutropenia in patients with reduced renal function. Mild reversible creatinine changes are possible.

Management

Reduce the starting dose for moderate (CrCl 30-59: 0.75 mg daily) and severe (CrCl 15-29: 0.5 mg daily) renal impairment per label; manage cytopenias with dose holds/reductions, transfusion, and growth-factor support.

Risk factors

  • Moderate to severe renal impairment (exposure)
  • Concurrent myelosuppressive therapy
  • Concurrent P-gp/BCRP inhibitors

Prevention

  • Renal-function-based starting-dose adjustment

Renal dose adjustment

Breast-cancer monotherapy: CrCl 60-89 no change; CrCl 30-59 reduce to 0.75 mg once daily; CrCl 15-29 reduce to 0.5 mg once daily. With enzalutamide in mCRPC, label-specific lower doses apply. Not studied on dialysis or in CrCl <15 mL/min.

Dialyzability & ESKD dosing

Renally cleared but highly protein-bound; dialyzability not formally established and no validated ESKD dose — avoid or use only with intensive hematologic monitoring.

Differential diagnosis

Cytopenias in a CKD patient on talazoparib usually reflect drug over-exposure (PK), not marrow infiltration or a separate renal lesion. A mild creatinine rise is more likely transporter-mediated than true AKI.

Monitoring

  • CBC monthly (and more often after dose changes) — anemia is the most common grade >=3 event
  • Blood counts more closely in CKD

Key trials & series

  • EMBRACA (gBRCA HER2-negative breast cancer)
  • TALAPRO-2 (talazoparib + enzalutamide in mCRPC)
  • Durairaj 2021 dedicated renal-impairment PK study

Clinical pearls

  • Talazoparib is the renally cleared PARP inhibitor — reduce the dose for CrCl <60 mL/min and watch counts, since exposure (and anemia) climbs as GFR falls.
  • The principal renal issue is dosing in CKD, not de novo kidney injury.
  • Confirm an ambiguous creatinine rise with cystatin C before attributing GFR decline.

Anticancer mechanism

One of the most potent PARP-trapping inhibitors; exploits homologous-recombination deficiency for synthetic lethality. Used in germline BRCA-mutated HER2-negative breast cancer and, with enzalutamide, in metastatic castration-resistant prostate cancer.

Guidelines & consensus

Each recommendation below is this atlas's faithful summary of the source, not a quotation from it — follow the PubMed link for the wording the society published. Summaries may be superseded; consult the current full text and individualize to the patient.

  • ADQI (2026) — The nephrotoxic effects of anti-cancer therapies: consensus report of the 34th Acute Disease Quality Initiative workgroupProvides expert-based statements (modified Delphi) on preventing and managing cisplatin/platinum-associated AKI, including isotonic IV hydration, attention to volume status and concomitant nephrotoxins, and incorporates evidence that IV magnesium supplementation may reduce cisplatin-associated AKI; emphasizes risk stratification and standardized AKI definitions.Nat Rev Nephrol · PMID 41361704
  • SIRM (2022) — SIRM-SIN-AIOM: appropriateness criteria for evaluation and prevention of renal damage in the patient undergoing contrast medium examinations-consensus statements from Italian College of Radiology (SIRM), Italian College of Nephrology (SIN) and Italian Association of Medical Oncology (AIOM)Recommends eGFR-based renal risk assessment and pre/post-contrast isotonic saline or sodium bicarbonate hydration; advises maintaining a 5-7 day interval between iodinated contrast administration and cisplatin in cancer patients to reduce additive nephrotoxicity.Radiol Med · PMID 35303246
  • KDIGO (2020) — KDIGO Controversies Conference on onco-nephrology: understanding kidney impairment and solid-organ malignancies, and managing kidney cancerIdentifies platinum compounds (especially cisplatin) as leading cytotoxic causes of acute tubular injury, AKI, and electrolyte/magnesium wasting; calls for interdisciplinary onco-nephrology care, accurate GFR estimation, and individualized drug dosing in patients with reduced kidney function.Kidney Int · PMID 33126977
  • KDIGO (2020) — KDIGO Controversies Conference on onco-nephrology: kidney disease in hematological malignancies and the burden of cancer after kidney transplantationAddresses chemotherapy-associated AKI/CKD in hematologic cancer, GFR estimation and chemotherapy dosing in patients with reduced kidney function, and management priorities and research gaps for onco-nephrology care.Kidney Int · PMID 33276867
  • ADDIKD (2025) — Integrating International Consensus Guidelines for Anticancer Drug Dosing in Kidney Dysfunction (ADDIKD) into everyday practiceProvides GRADE-based, drug-specific dose-adjustment recommendations for anticancer agents in kidney dysfunction (illustrated for methotrexate, cisplatin, carboplatin and nivolumab); the recommendations build on Part 1's standardised CKD-EPI eGFR assessment rather than Cockcroft-Gault creatinine clearance.EClinicalMedicine · PMID 40290844
  • ADDIKD (2025) — Aligning kidney function assessment in patients with cancer to global practices in internal medicineThree consensus recommendations: assess kidney function by GFR (measured GFR or CKD-EPI eGFR), classify it using KDIGO categories, and use this uniform approach to dose anticancer drugs — moving cancer medicine away from Cockcroft-Gault estimated creatinine clearance.EClinicalMedicine · PMID 40290845
  • ADDIKD (2025) — A methodology for determining dosing recommendations for anticancer drugs in patients with reduced kidney functionEstablishes that, where RCT evidence is lacking, anticancer drug dosing recommendations in kidney dysfunction should be derived by critically appraising observational literature via GRADE combined with structured international multidisciplinary consensus voting.EClinicalMedicine · PMID 40290846
  • KDIGO (2013) — Diagnosis, evaluation, and management of acute kidney injury: a KDIGO summary (Part 1)Defines/stages AKI by serum creatinine and urine output; emphasizes avoiding nephrotoxins, maintaining euvolemia/perfusion, dose-adjusting drugs to kidney function, and monitoring high-risk patients — the framework applied to nephrotoxic anti-cancer agents.Crit Care · PMID 23394211
  • KDIGO (2024) — Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease: known knowns and known unknownsEvaluate and risk-stratify CKD, manage to delay progression and its complications, and practise explicit medication management and drug stewardship — the framework the atlas's G1–G5 eGFR banding and every renal dose-adjustment recommendation sit inside. Because the guideline excludes dialysis and transplant recipients by its own statement of scope, its recommendations do not carry to those settings, where this atlas's dialyzability and post-transplant guidance rests on other sources.Kidney Int · PMID 38519239
  • KDIGO (2021) — Executive summary of the KDIGO 2021 Guideline for the Management of Glomerular DiseasesProvides the staging/treatment framework for drug-associated glomerular lesions (e.g., bisphosphonate- and interferon-related collapsing FSGS, VEGF-inhibitor podocytopathy/proteinuria), including immunosuppression and supportive RAAS-blockade strategies.Kidney Int · PMID 34556300
  • KDIGO (2024) — Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of ANCA-Associated VasculitisUpdates immunosuppressive induction (rituximab/cyclophosphamide), incorporates avacopan and lower-dose or glucocorticoid-sparing regimens — the management framework for drug- and checkpoint-inhibitor-associated ANCA/pauci-immune glomerulonephritis.Kidney Int · PMID 38388147
  • KDIGO (2024) — Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of Lupus NephritisUpdates first-line lupus nephritis therapy to combination immunosuppression with the addition of belimumab or a calcineurin inhibitor (voclosporin) — informs management of immune-complex/lupus-like glomerulonephritis encountered with immunotherapy.Kidney Int · PMID 38182299
  • KDIGO (2025) — Executive summary of the KDIGO 2025 Clinical Practice Guideline for the Management of Immunoglobulin A Nephropathy (IgAN) and Immunoglobulin A Vasculitis (IgAV)Encourages liberal kidney biopsy and stricter proteinuria control (<0.5 g/d, ideally <0.3 g/d) with RAAS blockers, SGLT2 inhibitors, and targeted-release budesonide — the framework for IgA-dominant glomerular lesions, including those triggered by immune-modulating cancer therapy.Kidney Int · PMID 40975525

References

6 peer-reviewed references. Citation metadata via PubMed / NLM.

  1. 1.The Effect of Renal Impairment on the Pharmacokinetics and Safety of Talazoparib in Patients with Advanced Solid Tumors.Durairaj C et al. · Clin Pharmacokinet · 2021 · PMID 33686631
  2. 2.Population Pharmacokinetics of Talazoparib in Patients With Advanced Cancer.Yu Y et al. · J Clin Pharmacol · 2019 · PMID 31489639
  3. 3.PARP Inhibitors and the Risk of Serum Creatinine Elevation in Ovarian Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.Gasowska-Bodnar A et al. · Cancers (Basel) · 2026 · PMID 42073552
  4. 4.Exploring and comparing renal adverse effects between PARP inhibitors based on a real-world analysis of post-marketing surveillance data.Xu Q et al. · Front Med (Lausanne) · 2024 · PMID 39493722
  5. 5.Targeted Cancer Therapies Causing Elevations in Serum Creatinine Through Tubular Secretion Inhibition: A Case Report and Review of the Literature.Mach T et al. · Can J Kidney Health Dis · 2022 · PMID 35756332
  6. 6.Talazoparib in Patients with Advanced Breast Cancer and a Germline BRCA Mutation.Litton JK et al. · N Engl J Med · 2018 · PMID 30110579
Educational monograph from NephTox (nephtox.com). Not medical advice — verify against current guidelines before any clinical decision.