Can Bactrim (trimethoprim/sulfamethoxazole) cause hyponatremia?

Bactrim (Trimethoprim/Sulfamethoxazole) Can Cause Hyponatremia

Yes, Bactrim (trimethoprim/sulfamethoxazole) can cause hyponatremia, which can be severe and symptomatic, particularly in high-risk patients. 1

Mechanism and Risk

• Trimethoprim, a component of Bactrim, inhibits sodium ion influx via the epithelial sodium channel in the cortical collecting duct, leading to decreased sodium reabsorption 2
• The FDA drug label specifically warns that "severe and symptomatic hyponatremia can occur in patients receiving sulfamethoxazole and trimethoprim," particularly when used for Pneumocystis jirovecii pneumonia treatment 1
• Hyponatremia is more common with high-dose therapy but can occur even with standard dosing regimens 3

Clinical Presentation

• Hyponatremia induced by TMP/SMX typically manifests as:
  • Nausea (41.7% of cases)
  • Vomiting (29.2% of cases)
  • Asymptomatic hyponatremia (20.8% of cases) 3
• Severe cases may present with lethargy, confusion, seizures, or altered mental status 4, 5
• The median serum sodium concentration in affected patients is approximately 118 mmol/L (range: 101-128.1 mmol/L) 3

Time Course and Resolution

• Hyponatremia typically develops within 3-10 days of starting TMP/SMX therapy (median 5 days) 3
• Upon discontinuation of the medication, serum sodium levels usually normalize within 2-14 days (median 4 days) 3

Risk Factors

• Advanced age 1, 5
• Renal impairment 1
• Concomitant use of other medications that can cause hyponatremia 5
• High-dose therapy, particularly for Pneumocystis jirovecii pneumonia 1
• Concomitant use of diuretics, especially thiazides 1
• Concurrent use of spironolactone (increases risk of both hyponatremia and hyperkalemia) 5

Additional Considerations

• TMP/SMX can also cause hyperkalemia through the same mechanism, as trimethoprim acts like the potassium-sparing diuretic amiloride 6
• The combination of hyponatremia and hyperkalemia can be particularly dangerous 4
• In patients with cirrhosis, hyponatremia is already a common complication, and TMP/SMX may worsen this condition 7

Monitoring and Management

• Electrolyte monitoring is recommended for all patients on TMP/SMX therapy, especially those with risk factors 3
• If symptomatic or severe hyponatremia develops, discontinuation of TMP/SMX should be considered 4, 2
• Evaluation for hyponatremia and appropriate correction is necessary in symptomatic patients to prevent life-threatening complications 1
• Ensure adequate fluid intake during treatment to prevent crystalluria, but be cautious about excessive free water intake in patients at risk for hyponatremia 1

Prevention

• Consider alternative antibiotics in patients with multiple risk factors for hyponatremia 1
• Avoid concurrent use of TMP/SMX with other medications known to cause hyponatremia when possible 5
• Monitor electrolytes before and during therapy, particularly in high-risk patients 3