Can losartan (angiotensin II receptor antagonist) cause hyponatremia in patients, especially those with underlying kidney issues or a history of cardiovascular disease, hypertension, or heart failure?

Can Losartan Cause Hyponatremia?

Yes, losartan can cause hyponatremia, though this is a rare adverse effect that typically occurs in specific clinical contexts, particularly when combined with diuretics or in patients with heart failure who consume excessive hypotonic fluids.

Mechanism and Clinical Context

While the FDA label for losartan does not list hyponatremia as a primary adverse effect 1, the clinical reality is more nuanced:

• Hyponatremia is primarily associated with diuretic therapy in patients taking ARBs like losartan, rather than being a direct effect of the ARB itself 2
• The European Society of Cardiology guidelines specifically warn patients on diuretics (often combined with ACE inhibitors or ARBs) to avoid excessive consumption of hypotonic fluids, which can cause hyponatremia 2
• A documented case report describes severe hyponatremia (sodium 123 mEq/L) in a 73-year-old diabetic patient on losartan monotherapy after 3.5 months, with Naranjo probability scale indicating "probable" causation 3

Risk Factors and High-Risk Populations

Patients at highest risk for developing hyponatremia on losartan include:

• Those on concomitant diuretic therapy (loop or thiazide diuretics), where the combination creates additive risk 2
• Patients with heart failure who are volume overloaded and may be advised to restrict fluids 2
• Volume-depleted patients who may develop symptomatic hypotension and electrolyte disturbances 1
• Elderly patients with multiple comorbidities 3

Management Algorithm for Hyponatremia in Patients on Losartan

When hyponatremia develops in a patient taking losartan:

Volume-Depleted Patients:

• Stop thiazide diuretic or switch to loop diuretic if possible 2
• Reduce dose or stop loop diuretics if feasible 2
• Assess volume status and correct depletion 2

Volume-Overloaded Patients:

• Implement fluid restriction 2
• Increase dose of loop diuretic to promote free water excretion 2
• Consider AVP antagonist (e.g., tolvaptan if available) 2
• Consider IV inotropic support or ultrafiltration in severe cases 2

Monitoring Recommendations

Essential monitoring parameters include:

• Check renal function and electrolytes (including sodium) at baseline 2
• Recheck blood chemistry 1-2 weeks after initiation and after any dose increase 2
• The American Heart Association recommends checking serum creatinine and potassium (though sodium monitoring is equally important) within 2-4 weeks after initiation or dose increase 4
• Monitor more frequently in patients with renal dysfunction (eGFR <30 mL/min/1.73 m²) 2

Critical Pitfalls to Avoid

• Do not ignore patient education: Specifically counsel patients on diuretics with ARBs to avoid excessive water intake in response to thirst, as this can precipitate dilutional hyponatremia 2
• Avoid triple RAAS blockade: Never combine losartan with ACE inhibitors and aldosterone antagonists simultaneously, as this compounds electrolyte disturbances including hyponatremia risk 2, 4
• Recognize that hyponatremia may be multifactorial: In heart failure patients, the hyponatremia may result from the combination of neurohormonal activation, diuretic use, and the ARB rather than losartan alone 2

Clinical Significance

While hyponatremia is not a common adverse effect of losartan monotherapy, the documented case report demonstrates it can occur 3. The more common scenario is hyponatremia developing in the context of combination therapy with diuretics, where both medications contribute to the electrolyte disturbance 2. Clinicians should maintain vigilance for this adverse effect, particularly in elderly patients, those on diuretics, and patients with heart failure.