What are the precautions when using indomethacin (Nonsteroidal Anti-Inflammatory Drug (NSAID)) and lisinopril (Angiotensin-Converting Enzyme (ACE) inhibitor) together?

Precautions When Using Indomethacin and Lisinopril Together

The combination of indomethacin (NSAID) and lisinopril (ACE inhibitor) should be avoided when possible due to significant risks of acute kidney injury, hyperkalemia, and reduced antihypertensive efficacy, particularly in elderly, volume-depleted, or renally impaired patients. 1

Major Risks of Combination Therapy

Renal Function Impairment

• NSAIDs like indomethacin can cause deterioration of renal function when combined with ACE inhibitors like lisinopril 1
• This effect is particularly pronounced in:
  • Elderly patients (age >60 years)
  • Volume-depleted patients (including those on diuretics)
  • Patients with pre-existing kidney disease
  • Patients with heart failure 2
• Monitor renal function closely when this combination cannot be avoided
• Effects are usually reversible upon discontinuation of either medication 1

Reduced Antihypertensive Efficacy

• Indomethacin can significantly reduce the blood pressure-lowering effect of lisinopril 1, 3
• In a study of hypertensive osteoarthritic patients, diclofenac (another NSAID) significantly reduced the antihypertensive efficacy of lisinopril in both diabetic and non-diabetic patients 3
• The average increase in mean arterial pressure with NSAID use is 5-10 mmHg 2

Hyperkalemia Risk

• Both medications can increase serum potassium levels
• ACE inhibitors like lisinopril increase potassium by decreasing aldosterone production
• NSAIDs can reduce renal potassium excretion
• The combination significantly increases the risk of hyperkalemia 4
• In one study, severe hyperkalemia occurred in 3 out of 10 patients on the combination therapy 4

Monitoring Recommendations

When the combination cannot be avoided:

1. Renal Function Monitoring:

   • Check baseline BUN and creatinine before starting therapy
   • Monitor renal function within 1-2 weeks of initiation
   • Continue periodic monitoring (every 3 months) 5
   • Discontinue if BUN or creatinine doubles 5

2. Blood Pressure Monitoring:

   • Monitor blood pressure regularly
   • Discontinue NSAIDs if hypertension develops or worsens 5

3. Electrolyte Monitoring:

   • Check baseline serum potassium
   • Monitor potassium levels periodically, especially in high-risk patients
   • Be vigilant for signs of hyperkalemia (muscle weakness, paresthesia, cardiac arrhythmias)

Alternative Approaches

When possible, consider these alternatives:

1. Alternative Analgesics:

   • Acetaminophen (up to 4g/day) as first-line for mild to moderate pain 2
   • Topical NSAIDs for localized pain (minimal systemic absorption)
   • Topical lidocaine or capsaicin for localized pain 2

2. If NSAID Must Be Used:

   • Use the lowest effective dose for the shortest duration
   • Consider COX-2 selective inhibitors which may have less effect on renal function
   • Avoid indomethacin specifically, as it has more pronounced effects on renal function and blood pressure than other NSAIDs

Special Populations at Increased Risk

• Elderly patients (>60 years)
• Patients with heart failure
• Patients with chronic kidney disease
• Patients on diuretics
• Diabetic patients
• Patients with volume depletion

Clinical Pearls

• The combination can have an additive antiproteinuric effect in patients with nephrotic syndrome, but this potential benefit is outweighed by the risks of renal function deterioration and hyperkalemia 4
• Indomethacin has been associated with more CNS side effects (confusion, psychosis, cognitive changes) compared to other NSAIDs, especially in elderly patients 5
• If the combination must be used, consider temporarily reducing or discontinuing diuretics to minimize the risk of acute kidney injury 1
• The effects on renal function are usually reversible upon discontinuation of either medication 1

Remember that the risks of this drug combination are significant and should be carefully weighed against potential benefits, with close monitoring when the combination cannot be avoided.