Maximum Dose of Enalapril with Amlodipine
The maximum dose of enalapril is 40 mg daily (or 20 mg twice daily) and the maximum dose of amlodipine is 10 mg daily when used in combination for hypertension, even in patients with impaired renal function. 1
Standard Maximum Dosing
- Enalapril maximum dose: 40 mg/day (can be given as 20 mg twice daily or 40 mg once daily) 1
- Amlodipine maximum dose: 10 mg/day 1
- These maximum doses apply when the medications are used alone or in combination 1, 2
Combination Therapy Considerations
The combination of enalapril and amlodipine is a rational and effective pairing because ACE inhibitors and calcium channel blockers have different mechanisms of action that produce additive blood pressure reduction with fewer side effects than maximal doses of either drug alone. 1
- Fixed-dose combinations of ACE inhibitors with calcium channel blockers are FDA-approved and widely used, though enalapril-amlodipine specifically is not available as a fixed combination in the U.S. 1
- Studies demonstrate that amlodipine 10 mg added to enalapril produces significantly greater blood pressure reduction than enalapril alone, with good tolerability 2
Dosing in Renal Impairment
In patients with impaired renal function, enalapril dosing should be reduced based on creatinine clearance, but amlodipine requires no dose adjustment. 3, 4
Enalapril dose adjustment for renal dysfunction:
- Creatinine clearance 10-25 mL/min: Start at 2.5 mg daily, maximum 10-20 mg daily 3
- Creatinine clearance 25-45 mL/min: Start at 5 mg daily, maximum 20 mg daily 3
- Creatinine clearance >45 mL/min: Standard dosing up to 40 mg daily 3
Amlodipine in renal dysfunction:
- No dose adjustment needed regardless of renal function 4
- Amlodipine 2.5-5 mg daily is effective and safe in hypertensive patients with renal dysfunction, with no drug accumulation observed 4
- Amlodipine provides comparable renoprotection to ACE inhibitors in patients with chronic kidney disease 5
Titration and Monitoring
Allow at least 4 weeks between dose increases to observe full antihypertensive response, unless more urgent blood pressure reduction is required. 1
- Most hypertensive patients require combination therapy to achieve optimal blood pressure control 1
- Submaximal doses of two drugs (e.g., enalapril 10-20 mg + amlodipine 5 mg) often produce better blood pressure reduction with fewer side effects than maximal monotherapy 1
- Monitor serum creatinine and potassium within 7-14 days after initiating or increasing enalapril dose, then at least annually 6, 7
Critical Safety Considerations
Accept creatinine increases up to 20-30% from baseline after ACE inhibitor initiation—this reflects beneficial hemodynamic effects on the kidney, not harm. 1, 7
- Discontinue or reduce enalapril if serum creatinine increases >30% from baseline or if potassium rises above 5.5-6.0 mEq/L 7
- Amlodipine may cause peripheral edema, which is dose-dependent and occurs more frequently at 10 mg daily 1
- The combination is generally well-tolerated, with complementary side effect profiles (ACE inhibitors can cause hyperkalemia; calcium channel blockers do not) 1, 2
Blood Pressure Targets
Target blood pressure <130/80 mmHg for most patients with hypertension, including those with diabetes or chronic kidney disease. 6, 8, 7