Can Edarbi (azilsartan) cause hyponatremia?

Can Edarbi (Azilsartan) Cause Hyponatremia?

Yes, Edarbi (azilsartan) can potentially cause hyponatremia, although it is not among the most common causes of diuretic-induced hyponatremia compared to thiazide diuretics.

Mechanism and Risk Assessment

Azilsartan is an angiotensin II receptor blocker (ARB) listed in clinical guidelines for hypertension management 1. ARBs can contribute to hyponatremia through several mechanisms:

1. Blockade of the renin-angiotensin-aldosterone system (RAAS):

   • Inhibits aldosterone release, which can impair sodium reabsorption
   • May increase antidiuretic hormone (ADH) activity

2. Risk factors that increase susceptibility:

   • Concurrent use with diuretics (especially thiazides)
   • Advanced age
   • Renal impairment
   • Volume depletion

Evidence from Guidelines

The 2017 ACC/AHA Hypertension Guidelines list azilsartan among ARBs with potential for electrolyte disturbances 1. While the guidelines don't specifically highlight hyponatremia for azilsartan, they note that ARBs as a class can affect electrolyte balance, particularly when combined with other medications.

The European Society of Cardiology guidelines note that "volume depletion and hyponatremia from excessive diuresis may increase the risk of hypotension and renal dysfunction with ACEI/ARB therapy" 1. This indicates that the combination of ARBs with diuretics significantly increases the risk of hyponatremia.

Comparison with Other Medications

• Thiazide diuretics: Most commonly associated with hyponatremia (94% of severe cases) 2
• Loop diuretics: Less commonly cause hyponatremia than thiazides 2
• ARBs (including azilsartan): Can cause hyponatremia, though less frequently than thiazides when used as monotherapy

Case reports have documented severe hyponatremia with other ARBs such as losartan 3, suggesting a class effect that would include azilsartan.

Monitoring and Management

If a patient on Edarbi develops hyponatremia:

1. Assessment:

   • Check serum sodium, potassium, and renal function
   • Evaluate volume status
   • Consider other contributing medications or conditions

2. Management options:

   • For mild hyponatremia: Fluid restriction and close monitoring
   • For moderate to severe hyponatremia (Na+ <125 mmol/L): Consider dose reduction or discontinuation
   • For severe symptomatic hyponatremia (Na+ <120 mmol/L): Discontinue medication and provide appropriate sodium correction

3. Caution in correction:

   • Avoid rapid correction (>8 mmol/L per day) to prevent osmotic demyelination syndrome 2
   • Monitor more frequently in high-risk patients (elderly, renal impairment)

Clinical Pearls and Pitfalls

• Combination therapy risk: The risk of hyponatremia significantly increases when Edarbi is combined with diuretics, especially thiazides 1
• Monitoring frequency: Check electrolytes within 1-2 weeks after starting therapy and after dose adjustments 1
• Diagnostic confusion: ARB-induced hyponatremia may be mistaken for SIADH (Syndrome of Inappropriate ADH) 4
• Symptom recognition: Watch for neurological symptoms (confusion, drowsiness), which may indicate significant hyponatremia 3

While specific data on azilsartan-induced hyponatremia is limited compared to other ARBs, the class effect and mechanism of action suggest that clinicians should monitor for this potential adverse effect, particularly in high-risk patients or those on combination therapy.