Cyclophosphamide
Cytoxan · Oxazaphosphorine alkylator
Vasopressin-independent hyponatremia; hemorrhagic cystitis.
SIADHCYST
MildOpen →
Vinca alkaloid
Vinorelbine
Navelbine · VNR
A semisynthetic vinca alkaloid with documented SIADH case reports.
MildVinca alkaloid · approved 1994
Non-small-cell lung cancerBreast cancer
Signature kidney injury
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
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.
Onset
Days after dosing, sometimes after several cycles (one report after three cycles).
Reversibility
Reversible
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.
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
- Monitor serum sodium during therapy
- Limit hypotonic fluids in susceptible patients
- Plan controlled correction if hyponatremia develops
Note · SIADH reports define the renal signal; there is no characteristic direct nephrotoxicity.
Clinical depth
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.
Where it strikes
Nephron segments
Distal Tubule / Collecting Duct
Fine-tuning of Na, K, Mg, acid & water
Injury signatures
SIADH / HyponatremiaElectrolyte Wasting
Beyond the kidney
Class-level context for the major non-renal toxicities of vinca alkaloids.
Ophthalmic
Keratopathy, uveitis, retinopathy
- Visual disturbance (crizotinib)
Hepatic / Liver
Transaminitis, hepatitis, VOD/SOS
- Transaminitis
Neurologic
Neuropathy, encephalopathy, ICANS, PRES
- CNS effects (lorlatinib)
Evidence
5 peer-reviewed references. Citation metadata via PubMed / NLM.
LandmarkSyndrome of Inappropriate Antidiuretic Hormone after vinorelbine treatment.Hoang M et al. · J Oncol Pharm Pract 2013 · PMID 23353713Case report of vinorelbine-associated SIADH with life-threatening hyponatremia resolving after discontinuation.PMIDA real-world pharmacovigilance study using disproportionality analysis of FDA Adverse Event Reporting System events for vinca alkaloids: comparing vinorelbine and vincristine.Zhong C et al. · Expert Opin Drug Saf 2024 · PMID 39340205FAERS analysis identifying inappropriate ADH secretion among vinorelbine adverse events.PMIDPathophysiology of Drug-Induced Hyponatremia.Kim GH et al. · J Clin Med 2022 · PMID 36233678Mechanistic review of drug-induced SIADH/hyponatremia relevant to vinca alkaloids.PMIDDiagnosis and Management of Hyponatremia: A Review.Adrogué HJ et al. · JAMA 2022 · PMID 35852524Authoritative SIADH management guidance including safe correction limits.PMIDOnconephrology: The intersections between the kidney and cancer.Rosner MH et al. · CA Cancer J Clin 2020 · PMID 32853404Onconephrology review covering chemotherapy-associated electrolyte disorders including paraneoplastic and drug-induced SIADH.