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Vinca alkaloid

Vinorelbine

Navelbine · VNR

Vinca alkaloid · approved 1994 · 5 references

A semisynthetic vinca alkaloid with documented SIADH case reports.

Signature injury
SIADH / Hyponatremia
Severity
Mild
Reversibility
Reversible
Onset
Days after dosing, sometimes after several cycles (one report after three cycles).

Signature kidney injury & incidence

SIADH / Hyponatremia.

SIADH with hyponatremia is reported with vinorelbine at case level; FAERS pharmacovigilance analysis of vinca alkaloids flags inappropriate ADH secretion as a shared signal. Quantitative incidence is not established.

Source: Hoang et al., J Oncol Pharm Pract 2013

Reported injury signatures: SIADH / Hyponatremia, Electrolyte Disturbance.

Renal toxicity profile

  1. SIADH / HyponatremiaPrimary
  2. Electrolyte DisturbanceSecondary

Onset timing & rechallenge

Variable / unpredictable — Days after dosing, sometimes only after several cycles (one report after three).

Mechanism of kidney injury

Like other vinca alkaloids, induces inappropriate antidiuresis with increased collecting-duct water reabsorption, causing euvolemic dilutional hyponatremia rather than structural renal injury. In lung-cancer patients the underlying tumor can be an independent (paraneoplastic) cause of SIADH, complicating attribution.

Clinical presentation

Euvolemic hyponatremia, low serum osmolality, inappropriately concentrated urine (urine osm >100, urine Na >30); neurologic symptoms if severe or rapidly developing.

Management

Fluid restriction; 3% hypertonic saline for severe symptomatic cases with a safe correction rate (<=8 mmol/L/24 h). Withhold drug; SIADH typically resolves on discontinuation.

Risk factors

  • Other SIADH-promoting drugs/conditions
  • Excess free-water intake
  • Pulmonary malignancy (independent paraneoplastic SIADH cause)

Prevention

  • Limit hypotonic fluids in susceptible patients
  • Plan controlled correction if hyponatremia develops

Renal dose adjustment

Hepatically metabolized (CYP3A) and biliary excreted - no renal dose adjustment; reduce for hepatic impairment/hyperbilirubinemia. Never give intrathecally.

Dialyzability & ESKD dosing

Extensive tissue binding and large volume of distribution; not dialyzable. Hyponatremia is managed by fluid/sodium strategies.

Differential diagnosis

Drug-induced SIADH vs paraneoplastic ectopic ADH from lung cancer vs hypovolemic hyponatremia. In NSCLC, distinguishing tumor-driven from drug-driven SIADH may require temporal correlation with dosing and response to drug hold.

Monitoring

  • Serum sodium and osmolality during therapy
  • Urine osmolality/sodium if hyponatremia develops
  • CBC for neutropenia (primary dose-limiting toxicity)

Key trials & series

  • Hoang J Oncol Pharm Pract 2013 vinorelbine SIADH case report
  • Zhong Expert Opin Drug Saf 2024 FAERS analysis

Clinical pearls

  • In a lung-cancer patient, vinorelbine SIADH and tumor-related SIADH can coexist - timing relative to dosing helps attribute it.
  • Water restriction is first-line; reserve hypertonic saline for severe symptoms.
  • Resolution after holding the drug supports a drug cause.

Anticancer mechanism

Semisynthetic vinca alkaloid that inhibits microtubule assembly at the vinca-binding domain of tubulin and arrests mitosis. Used in non-small-cell lung cancer and breast cancer.

Note

SIADH reports define the renal signal; there is no characteristic direct nephrotoxicity.

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

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

  1. 1.Syndrome of Inappropriate Antidiuretic Hormone after vinorelbine treatment.Hoang M et al. · J Oncol Pharm Pract · 2013 · PMID 23353713
  2. 2.A real-world pharmacovigilance study using disproportionality analysis of United States Food and Drug Administration Adverse Event Reporting System events for vinca alkaloids: comparing vinorelbine and Vincristine.Zhong C et al. · Expert Opin Drug Saf · 2024 · PMID 39340205
  3. 3.Pathophysiology of Drug-Induced Hyponatremia.Kim GH et al. · J Clin Med · 2022 · PMID 36233678
  4. 4.Diagnosis and Management of Hyponatremia: A Review.Adrogué HJ et al. · JAMA · 2022 · PMID 35852524
  5. 5.Onconephrology: The intersections between the kidney and cancer.Rosner MH et al. · CA Cancer J Clin · 2020 · PMID 32853404

Case reports & series (2)

The weakest rung of clinical evidence — single-patient and small-series reports, strongest first. Each carries a heuristic strength grade (A Strong / B Moderate / C Limited) inferred from its abstract and journal, not a formal appraisal. Weigh well below the primary references above.

  1. C1.[C · Limited]Syndrome of inappropriate secretion of antidiuretic hormone after chemotherapy with vinorelbine.Kuroda H et al. · Cancer Chemother Pharmacol · 2008 · PMID 17989977
  2. C2.[C · Limited]Syndrome of inappropriate antidiuretic hormone secretion (SIADH) induced by vinorelbine treatment of metastatic breast cancer.Canzler U et al. · Onkologie · 2007 · PMID 17848819
Educational monograph from NephTox (nephtox.com). Not medical advice — verify against current guidelines before any clinical decision.