Can a patient on lisinopril (angiotensin-converting enzyme inhibitor) take Bactrim (trimethoprim/sulfamethoxazole)?

Concurrent Use of Lisinopril and Bactrim: Risk of Hyperkalemia

Patients taking lisinopril should avoid concurrent use of Bactrim (trimethoprim/sulfamethoxazole) due to the significant risk of hyperkalemia, which can lead to serious cardiac arrhythmias and potentially death. 1

Mechanism of Interaction

The interaction between these medications occurs through complementary mechanisms:

1. ACE inhibitors (Lisinopril): Decrease aldosterone production, reducing potassium excretion
2. Trimethoprim component of Bactrim: Blocks sodium channels in the distal nephron, inhibiting potassium secretion similar to potassium-sparing diuretics 1

This combination creates a "perfect storm" for potassium retention in the body.

Evidence Supporting This Contraindication

The European Society of Cardiology explicitly lists trimethoprim-sulfamethoxazole as a medication that can cause hyperkalemia in their expert consensus document on hyperkalaemia management 1. Additionally, the FDA drug label for sulfamethoxazole/trimethoprim specifically warns against concurrent use with ACE inhibitors, stating: "In the literature, three cases of hyperkalemia in elderly patients have been reported after concomitant intake of sulfamethoxazole and trimethoprim oral suspension and an angiotensin converting enzyme inhibitor." 2

Risk Factors for Hyperkalemia

The risk of hyperkalemia is particularly high in patients with:

• Renal impairment
• Diabetes mellitus
• Advanced age
• Concomitant use of other potassium-sparing medications
• Heart failure 1

Alternative Antibiotic Options

If a patient on lisinopril requires antibiotic therapy, consider these alternatives to Bactrim:

• Penicillins
• Cephalosporins
• Macrolides
• Tetracyclines
• Fluoroquinolones (with appropriate precautions)

Management Algorithm if Both Medications Must Be Used

In rare situations where no alternative antibiotic can be used:

1. Baseline Assessment:

   • Check serum potassium before starting Bactrim
   • Assess renal function (eGFR or creatinine)

2. Risk Stratification:

   • High risk: eGFR <30 mL/min, baseline K+ >4.5 mmol/L, elderly, diabetic, heart failure
   • Moderate risk: eGFR 30-60 mL/min
   • Lower risk: Normal renal function, young, no comorbidities

3. Management Based on Risk:

   • High risk: Consider temporarily holding lisinopril during short course of Bactrim
   • Moderate risk: Monitor potassium at 48-72 hours after starting Bactrim
   • Lower risk: Monitor potassium within one week

4. Potassium Management:

   • If K+ >5.0 mmol/L: Consider stopping one of the medications
   • If K+ >5.5 mmol/L: Discontinue both medications and treat hyperkalemia

Important Caveats

• The risk of hyperkalemia increases with the duration of concurrent therapy
• Patients with seemingly normal renal function may still develop hyperkalemia
• Symptoms of hyperkalemia (weakness, palpitations, paresthesias) may be subtle or absent until severe
• ECG changes may not be present until potassium levels are dangerously elevated

Conclusion

The combination of lisinopril and Bactrim poses a significant risk of hyperkalemia that can lead to serious cardiac complications. When possible, alternative antibiotics should be selected for patients on lisinopril. If the combination cannot be avoided, close monitoring of potassium levels is essential, with consideration of temporarily discontinuing lisinopril during the course of antibiotic therapy in high-risk patients.