Which anti-cancer drugs cause siadh / hyponatremia?

SIADH / Hyponatremia (SIADH) is the signature kidney injury of Selinexor, Cyclophosphamide, Melphalan, Temozolomide, Osimertinib, Vincristine, Vinblastine, Vinorelbine, Tamoxifen, Lazertinib, Vismodegib, Chlorambucil. It is also associated with Cisplatin, Pemetrexed, Interleukin-2 (high-dose), Cytarabine, Atezolizumab, Selpercatinib, Pentostatin, Nivolumab, Carboplatin, Sunvozertinib, Vinflunine, Dabrafenib.

The Injury Atlas

SIADH

SIADH / Hyponatremia

Inappropriate water retention at the collecting duct — high-dose cyclophosphamide.

12signature agents

Deep diveDrug-induced SIADH

Landmark evidence1 seminal study

Where it strikes

Distal Tubule / Collecting Duct

Fine-tuning of Na, K, Mg, acid & water

See it on the nephron

Agents’ overall severity

Each agent’s whole-drug severity grade, not the severity of this lesion specifically — an agent whose signature injury is elsewhere can still be graded severe here.

Moderate· 1Mild· 11

Agents’ overall reversibility

Reversible· 12

Does the kidney recover? Cross-drug outcomes

Agents’ onset window

How soon each agent’s kidney toxicity typically appears — a whole-drug tempo, not specific to this lesion.

Hyperacute (<24 h)· 1Acute (days)· 3Subacute (weeks)· 1Delayed (weeks–months)· 1Variable· 6

Real-world reporting for this lesion

FAERS across all lesions →

Agents with a disproportionate FAERS reporting signal for siadh / hyponatremia (reporting odds ratio with a 95% CI lower bound above 1) — a spontaneous-reporting signal, not incidence or proven causation. FAERS carries reporting and indication biases and has no denominator.

19Corroborated

Documented in the atlas profile and carrying a FAERS signal — the strongest claim the atlas makes.

1Documented, FAERS-silent

Documented in a profile with no reporting signal. Mostly expected: naming this lesion on a report can require a biopsy, and silence is not evidence against the literature.

67Not attributable

A real reporting signal that is not evidence for this drug-lesion pair: no MedDRA term names it, the naming subset asked alone came back flat, or the 2026-08 review attributed the reporting to the population, co-therapy, or class-level literature.

27Reported by name

The terms that name this lesion are disproportionate, but no profile documents it for that agent. Most are echoed by a sibling agent in the same class. Leads for review, never lesions the atlas claims.

5-Fluorouracil Acalabrutinib Afatinib Alpelisib Atezolizumab Axitinib Azacitidine Belzutifan Bevacizumab Bicalutamide Binimetinib Bleomycin Bortezomib Brentuximab vedotin Busulfan Cabazitaxel Cabozantinib Capecitabine Capmatinib Carboplatin Ceritinib Cetuximab Chlorambucil Cisplatin Cobimetinib Crizotinib Cyclophosphamide Cytarabine Dabrafenib Dacarbazine Darolutamide Dasatinib Dinutuximab Docetaxel Doxorubicin Durvalumab Encorafenib Enfortumab vedotin Epcoritamab Erdafitinib Erlotinib Etoposide Everolimus Fludarabine Futibatinib Gefitinib Gemcitabine Gemtuzumab ozogamicin Glasdegib Hydroxyurea Ibritumomab tiuxetan Ibrutinib Ifosfamide Imlunestrant Inavolisib Inotuzumab ozogamicin Interleukin-2 (high-dose)Ipilimumab Irinotecan Lanreotide Lenvatinib Lifileucel Lomustine (CCNU)Lurbinectedin Melphalan Mitotane Naxitamab Nelarabine Niraparib Nivolumab Octreotide Oxaliplatin Paclitaxel Pamidronate Panitumumab Pazopanib Pegaspargase Pembrolizumab Pemetrexed Pentostatin Polatuzumab vedotin Pralatrexate Pralsetinib Ramucirumab Regorafenib Relacorilant Ribociclib Rituximab Selinexor Sorafenib Sunitinib Talazoparib Tamoxifen Temozolomide Temsirolimus Tepotinib Thalidomide Thiotepa Tislelizumab Topotecan Trabectedin Trametinib Trastuzumab deruxtecan Trastuzumab emtansine (T-DM1)Tucatinib Vandetanib Vemurafenib Vinblastine Vincristine Vinorelbine Vismodegib Zolbetuximab Zoledronic acid

113 agents with a significant SIADH reporting signal.

Management approach

Full framework →

Manage the hyponatremia (fluid restriction, careful correction); avoid over-hydration around dosing.

Drug-level levers

Avoid the large hypotonic fluid loads historically given with cyclophosphamide.
Adjust dose timing and hydration strategy.

Pharmacologic toolkit

Fluid restriction — First line for euvolemic hyponatremia.
Careful sodium correction — Correct slowly to avoid osmotic demyelination syndrome.

When to biopsy

Not indicated — a water-handling disorder, not structural injury.

Monitoring

· Serum sodium around dosing
· Fluid balance

Grounding

Cyclophosphamide-associated hyponatremia / SIADH · PMID 26109089 ↗

Educational use only. Educational synthesis of the published literature — not a treatment protocol, dosing guide, or medical advice. Regimens and agents shown are illustrative of what the literature describes; verify against current guidelines (ASON / KDIGO / ASCO / NCCN) and individualize to the patient. Using this site creates no clinician–patient relationship.

Offending agents

Any agent24 Primary (#1) only12

Signature offenders

Agents for which siadh / hyponatremia is the defining renal lesion.

SelinexorEarly — within the first cycle/few weeks; front-loaded.Hyponatremia is common and dose-limiting. All-grade hyponatremia affected 39% of the selinexor-dexamethasone patients tabulated in the FDA label's STORM adverse-reaction table, reaching grade 3-4 in 22% — making it the leading grade >=3 non-hematologic toxicity, and one of the six grade 3-4 laboratory abnormalities the label lists at >=10%. Both rates come from the trial's safety tables rather than its abstract, which does not mention hyponatremia; a separate phase 1 dose-escalation cohort reported grade >=3 hyponatremia at a concordant 23%. Combination regimens run lower: in BOSTON grade 3-4 hyponatremia was ~8-9%, and in SADAL ~8%.Moderate CyclophosphamideHyponatremia within hours; cystitis acute.Dose-related hyponatremia (not reliably quantified); hemorrhagic cystitis ~5–20%, lower with mesna prophylaxis. Reported rate: hyponatremia in 52% — 69 adults who received high-dose cyclophosphamide therapy at a single center 2010-2014 (retrospective cohort (Bonella 2017, PMID 29890094).Mild MelphalanDays after high-dose administration.High-dose intravenous melphalan can cause hyponatremia/SIADH; in a small high-dose series most patients showed declining sodium, but this is reported at case/series level rather than as a large quantified rate. Melphalan PK is not adversely affected by renal failure, so transplant in renal impairment is feasible.Mild TemozolomideDuring cycles of therapy; variable.Generally renally well tolerated; renal clearance of the parent drug is a minor elimination pathway and dedicated PubMed searches for temozolomide nephrotoxicity/SIADH return essentially no indexed series. Hyponatremia/SIADH is an occasional, case/toxicity-table-level event, and rare acute interstitial nephritis has been reported in combination contexts.Mild OsimertinibReported within roughly the first weeks to a few months of therapy (around two months in several published cases).Syndrome of inappropriate antidiuretic hormone (SIADH)-type hyponatremia is described at the case level; occasional acute kidney injury and rare proteinuria are reported. True structural kidney injury is not quantified as a discrete endpoint in randomized data, where overall renal adverse events are uncommon. The common osimertinib renal finding is instead a pseudo-decrease in creatinine-based eGFR from inhibited tubular creatinine secretion, quantified for osimertinib specifically by Ilyas et al. (Kidney Med 2026) and, at the cohort level, in the AMBORA real-world analysis: among 238 patients on 38 oral antitumor agents likely to cause pseudo-worsening, mean eGFR fell 6.8 mL/min within 30 days and by >=20 mL/min in 17.2% — a whole-group figure, not an osimertinib-specific rate.Mild VincristineDays after dosing, often within the first 1-2 cycles; resolves after the drug is withheld.Vincristine-associated SIADH with hyponatremia is a recognized but uncommon, largely case-level adverse effect; a global pharmacovigilance analysis estimated a reporting rate of about 1.3 per 100,000 treated patients, with a possible over-representation in Asian patients. FAERS disproportionality analysis also flags inappropriate ADH secretion as a vinca-class signal.Mild VinblastineDays after administration, generally within the first cycles.Vinblastine can cause SIADH with hyponatremia; this is a recognized class effect reported at case level rather than as a quantified rate. Rare Raynaud phenomenon and other vascular events (especially in germ-cell regimens) are also described.Mild VinorelbineDays after dosing, sometimes after several cycles (one report after three cycles).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.Mild TamoxifenFlare hypercalcemia within the first days to weeks; hyponatremia case-level and variable.Direct nephrotoxicity is not a feature. Tumor-flare hypercalcemia occurs early in patients with osteolytic bone metastases (about 13% — 12 of 93 — in one hypercalcemic breast-cancer series). Euvolemic hyponatremia (SIADH-type) is reported only at the case level.Mild LazertinibDuring therapy; case-level and variable.Hyponatremia is a recognized signal of third-generation EGFR TKIs (an osimertinib-class effect); for lazertinib specifically the renal/sodium data are limited and not well quantified. EGFR blockade also causes electrolyte wasting (hypomagnesemia, hypokalemia), and combination with amivantamab adds to these effects.Mild VismodegibMuscle spasms within the first weeks-to-months; hyponatremia is sporadic and variable in timing.Muscle spasms are near-universal (~64-71%), with dysgeusia and alopecia close behind; hyponatremia is reported but uncommon and not precisely quantified for an SIADH mechanism. Direct kidney injury is rare.Mild ChlorambucilHyponatremia, when reported, has occurred during ongoing dosing, including with low doses; timing is variable.Chlorambucil has minimal direct nephrotoxicity. Drug-associated SIADH with hyponatremia is reported only rarely, in isolated case reports; tumor lysis is uncommon given its indolent-disease indications and gradual cytoreduction. No reliable incidence figure exists.Mild

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