Methotrexate and Hyponatremia
Methotrexate is not recognized as a cause of hyponatremia in established clinical guidelines or its known adverse effect profile.
Evidence from Guidelines
The comprehensive adverse effect profile of methotrexate documented in major dermatology and rheumatology guidelines does not include hyponatremia or electrolyte disturbances as recognized toxicities 1, 2.
The well-established toxicities of methotrexate include:
- Hematologic toxicity: Pancytopenia, thrombocytopenia, leukopenia, and myelosuppression 1, 3, 2
- Hepatotoxicity: Liver fibrosis and cirrhosis with cumulative dosing 1, 3
- Nephrotoxicity: Acute kidney injury, particularly with high-dose methotrexate, and potential chronic renal impairment 3, 4, 5, 6
- Pulmonary toxicity: Pneumonitis 1, 2
- Gastrointestinal effects: Mucositis, nausea, vomiting, and stomatitis 1, 2, 4
- Dermatologic toxicity 4
Monitoring Parameters
The American Academy of Dermatology and British Association of Dermatologists recommend specific monitoring for methotrexate therapy, which focuses on 1, 3:
- Complete blood count with differential
- Liver function tests (AST, ALT, albumin, bilirubin)
- Renal function (creatinine, calculated GFR)
Notably, serum sodium or electrolyte monitoring is not included in standard methotrexate surveillance protocols 1, 3.
Clinical Context
While methotrexate can cause renal dysfunction (both acute kidney injury with high doses and potential chronic impairment with low-dose therapy) 4, 5, 6, 7, hyponatremia is not a documented consequence of this nephrotoxicity. The renal effects of methotrexate primarily involve tubular crystallization and interstitial fibrosis rather than disturbances in sodium handling 4, 5.
Important Caveat
If hyponatremia occurs in a patient taking methotrexate, investigate alternative causes including 8:
- Other medications (antidepressants, antiepileptics, diuretics)
- Underlying disease states
- Volume status abnormalities
- Syndrome of inappropriate antidiuretic hormone secretion (SIADH)
The hyponatremia should not be attributed to methotrexate itself based on current evidence.