At what glomerular filtration rate (GFR) should Enalapril (Enalapril maleate) dosage be reduced?

From the Guidelines

Enalapril dosage should be reduced when the glomerular filtration rate (GFR) falls below 45 mL/min/1.73m², as recommended by the 2014 American Journal of Kidney Diseases guideline 1.

Key Considerations

• The guideline suggests starting at a lower dose in people with GFR < 45 mL/min/1.73m² when using RAAS antagonists, such as Enalapril, to minimize the risk of adverse effects 1.
• It is essential to assess GFR and measure serum potassium within 1 week of starting or following any dose escalation of Enalapril, especially in patients with reduced renal function 1.
• The guideline does not recommend routinely discontinuing Enalapril in people with GFR < 30 mL/min/1.73m², as it remains nephroprotective, but careful monitoring and dose adjustment are necessary to avoid potential complications 1.

Dosage Adjustment

• For patients with a GFR between 30-45 mL/min/1.73m², the recommended starting dose of Enalapril may need to be reduced, with careful titration based on blood pressure response.
• For patients with severe renal impairment (GFR < 30 mL/min/1.73m²), the initial dose should be reduced, and close monitoring of blood pressure, serum potassium, and renal function is essential.

Monitoring and Precautions

• Regular monitoring of blood pressure, serum potassium, and renal function is crucial when using Enalapril in patients with reduced GFR to minimize the risk of adverse effects, such as excessive hypotension, hyperkalemia, or worsening renal function 1.
• Enalapril should be temporarily suspended during intercurrent illness, planned IV radiocontrast administration, bowel preparation prior to colonoscopy, or prior to major surgery to avoid potential complications 1.

From the FDA Drug Label

Normal Renal Function > 80 mL/min 5 mg Mild Impairment ≤ 80 > 30 mL/min 5 mg Moderate to Severe Impairment ≤ 30 mL/min 2.5 mg

The Enalapril dosage should be reduced at a glomerular filtration rate (GFR) of ≤ 30 mL/min.

• For patients with mild impairment (GFR ≤ 80 > 30 mL/min), the initial dose is 5 mg.
• For patients with moderate to severe impairment (GFR ≤ 30 mL/min), the initial dose is 2.5 mg. 2

From the Research

Enalapril Dosage Reduction in Renal Impoucher

• The dosage of Enalapril should be reduced in patients with renal insufficiency, as most angiotensin-converting enzyme (ACE) inhibitors and their metabolites are excreted renally 3.
• A study found that patients with chronic renal failure given small or moderately high doses of enalapril may have markedly elevated levels of serum enalaprilat, and the clearance of enalaprilat correlated linearly with GFR (r=0.86, p=0.003) 3.
• Another study suggested that a low concentration of enalaprilat afforded the same degree of renoprotection, blood pressure control, and minimization of proteinuria as a high concentration in patients with moderate to severe renal insufficiency 4.
• The study also found that the high-dosage treatment was associated with a more pronounced tendency to hyperkalaemia, and there seems to be no indication for increasing the daily dose of enalapril beyond what achieves adequate blood pressure control in this group of patients 4.
• A pharmacokinetic study is recommended during the development phase of a new drug that is likely to be used in patients with renal dysfunction and whose pharmacokinetics are likely to be significantly altered in these patients 5.
• Dosage adjustment based on GFR may not always be appropriate, and a re-evaluation of markers of renal function may be required 5.
• In patients with moderate to severe chronic nephropathy, the initial effect of enalapril on kidney function was a fall in GFR, which was clinically acceptable in most patients 6.
• The median change in GFR was -14% (range -44% to +10%) after starting enalapril, and the split renal function was unchanged 6.
• Electronic prescribing and automated reporting of estimated glomerular filtration rate (eGFR) may help reduce medication errors, but patients with renal insufficiency may still be exposed to inappropriate drug use 7.

GFR Threshold for Dosage Reduction

• A GFR threshold for reducing Enalapril dosage is not explicitly stated in the studies, but it is suggested that dosage adjustment should be based on the remaining kidney function, most often estimated on the basis of the patient's GFR 5.
• A study found that patients with GFR <30 ml/minute had a marked elevation of serum enalaprilat 3.
• Another study found that patients with moderate to severe renal insufficiency (GFR 17 ml/min/1.73 m2) may benefit from a low concentration of enalaprilat 4.
• Therefore, it is likely that the Enalapril dosage should be reduced in patients with GFR <30 ml/minute, but the exact threshold may vary depending on individual patient factors and clinical guidelines.