Pacritinib

Prerenal / Hemodynamic AKI.

Pacritinib has no established intrinsic nephrotoxicity; its renal risk is a downstream consequence of its dominant gastrointestinal toxicity. Diarrhea is the signature adverse effect — in the phase 2 study grade 1/2 diarrhea occurred in ~69% of patients and nausea in ~49% (Komrokji 2015), and in the PERSIST-1 phase 3 trial grade 3-4 diarrhea occurred in ~5%. In real-world FAERS pharmacovigilance, gastrointestinal disorders were the top disproportionality system-organ-class and diarrhea the most-reported preferred term (Zhang 2025). High-volume diarrhea (often with nausea/vomiting) can precipitate volume depletion, hypokalemia/hypomagnesemia, and prerenal azotemia, but a specific incidence of pacritinib-attributable acute kidney injury has not been separately quantified — so no headline AKI rate is reported here (incidencePct null).

Source: 25762180

Reported injury signatures: Prerenal / Hemodynamic AKI, Electrolyte Disturbance.

1. Prerenal / Hemodynamic AKIPrimary
2. Electrolyte DisturbanceSecondary

Subacute (~1–6 weeks) — Diarrhea (and the prerenal azotemia/electrolyte loss that tracks it) emerges within the first days-to-weeks and is most pronounced over roughly the first 8 weeks — early and episodic, not cumulative.

• Severe or persistent diarrhea (grade 3-4) and concurrent nausea/vomiting limiting oral rehydration
• Baseline volume depletion or poor oral intake
• Concomitant diuretics, ACE inhibitors/ARBs, or other nephrotoxins
• Older age and pre-existing chronic kidney disease
• Co-administration of other QT-prolonging drugs (electrolyte-arrhythmia interplay)
• Advanced myelofibrosis with poor performance status

• Start proactive antidiarrheal therapy (e.g., loperamide) at the first onset of diarrhea
• Encourage oral hydration and actively maintain volume status
• Check electrolytes (especially potassium and magnesium) and renal function at baseline and periodically, repleting promptly
• Review and minimize concomitant diuretics, RAAS blockers, and other nephrotoxins
• Interrupt or reduce the pacritinib dose per label for severe or refractory diarrhea before prerenal injury develops
• Avoid strong CYP3A4 inhibitors/inducers that alter pacritinib exposure

• Serum electrolytes — especially potassium and magnesium — at baseline and regularly, with prompt repletion (heightened importance because pacritinib prolongs the QT interval)
• Serum creatinine/BUN and volume/orthostatic status during and after diarrhea episodes
• Stool frequency and severity, plus body weight, as an early marker of impending volume loss
• ECG/QTc, particularly when electrolytes are deranged or with concomitant QT-prolonging drugs
• Complete blood count (thrombocytopenia and anemia are the on-target hematologic effects)

• PERSIST-2 (Mascarenhas 2018, JAMA Oncol) — registrational phase 3 in myelofibrosis with platelets <=100 x 10^9/L; basis for the 200 mg twice-daily accelerated approval, with diarrhea among the most common adverse events.
• PERSIST-1 (Mesa 2017, Lancet Haematol) — phase 3 versus best available therapy irrespective of baseline cytopenias; grade 3-4 diarrhea ~5%, with diarrhea the most common non-hematologic toxicity.
• Phase 2 study (Komrokji 2015, Blood) — grade 1/2 diarrhea ~69% and nausea ~49%, establishing GI toxicity as the dominant adverse effect and the driver of volume/electrolyte loss.
• FAERS disproportionality analysis (Zhang 2025, Front Oncol) — real-world post-marketing signal with gastrointestinal disorders as the leading system-organ-class and diarrhea the top reported term.

• The kidney injury is a downstream, functional consequence of pacritinib's dominant toxicity — diarrhea — not intrinsic nephrotoxicity; treat the gut and the volume/electrolyte deficit and the creatinine follows.
• Mind the QT-electrolyte loop: pacritinib prolongs the QT interval, and diarrhea-induced hypokalemia and hypomagnesemia amplify that risk — replete potassium and magnesium aggressively and check an ECG.
• Diarrhea is usually early (first weeks) and self-limited/manageable — pre-emptive loperamide and hydration prevent most prerenal events, so counsel patients before they start.
• Pacritinib's niche is myelofibrosis with severe thrombocytopenia (platelets <50 x 10^9/L) where ruxolitinib/fedratinib cannot be safely dosed; expect thrombocytopenia and anemia as on-target effects, with diarrhea as the manageable GI/renal-relevant toxicity.
• A FENa/urine-electrolyte check helps triage: a prerenal signature supports volume repletion over an expensive hunt for intrinsic renal disease.

• 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 (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