ACE Inhibitor Dosing for Hypertension
Standard Initial Doses for Adult Hypertension
For most adults with hypertension, start with lisinopril 10 mg once daily, enalapril 5 mg once daily, or ramipril 2.5 mg once daily, then titrate upward based on blood pressure response. 1, 2, 3
Specific ACE Inhibitor Dosing
| ACE Inhibitor | Initial Dose | Maximum Dose | Frequency |
|---|---|---|---|
| Captopril | 6.25 mg | 50 mg | Three times daily [4] |
| Enalapril | 2.5–5 mg | 10–20 mg | Twice daily [4,1] |
| Lisinopril | 2.5–10 mg | 20–40 mg | Once daily [4,2] |
| Ramipril | 1.25–2.5 mg | 10 mg | Once daily [4,3] |
| Fosinopril | 5–10 mg | 40 mg | Once daily [4] |
| Perindopril | 2 mg | 8–16 mg | Once daily [4] |
| Quinapril | 5 mg | 20 mg | Twice daily [4] |
| Trandolapril | 1 mg | 4 mg | Once daily [4] |
The usual dosage range for enalapril is 10–40 mg per day administered in a single dose or two divided doses, with some patients requiring twice-daily administration if the antihypertensive effect diminishes toward the end of the dosing interval. 1
Lisinopril doses up to 80 mg have been used but do not appear to give greater effect than 40 mg daily. 2
Adjustments for Patients Over 65 Years
In elderly patients (≥65 years), start with lower initial doses—lisinopril 2.5–5 mg once daily, enalapril 2.5 mg once daily, or ramipril 1.25 mg once daily—and titrate more gradually to minimize hypotension and falls. 5, 6, 7
Elderly patients aged 65–79 years should be treated to a target blood pressure <140/90 mmHg minimum, with consideration of <130/80 mmHg if well-tolerated. 4
For patients ≥80 years who are functionally independent, the same blood pressure targets apply (≥140/90 mmHg threshold for treatment initiation, target 120–129 mmHg systolic if tolerated), but start with monotherapy at lower doses. 8
In frail elderly patients ≥85 years, begin with monotherapy (preferably a dihydropyridine calcium channel blocker rather than an ACE inhibitor as first-line) and individualize targets based on tolerability, though the ≥140/90 mmHg treatment threshold remains. 8
Lower initial dosages (lisinopril 2.5 mg, enalapril 2.5 mg) are necessary in elderly persons to reduce the risk of hypotension and orthostatic symptoms. 6, 7
Adjustments for Impaired Renal Function
For patients with creatinine clearance ≤30 mL/min or serum creatinine ≥3 mg/dL, start with lisinopril 2.5 mg once daily, enalapril 2.5 mg once daily, or ramipril 1.25 mg once daily, and titrate cautiously. 1, 2, 3
Renal Dosing Guidelines
| Creatinine Clearance | Lisinopril Initial Dose | Enalapril Initial Dose | Ramipril Adjustment |
|---|---|---|---|
| >80 mL/min (normal) | 10 mg once daily [2] | 5 mg once daily [1] | Standard dosing [3] |
| 30–80 mL/min (mild impairment) | 10 mg once daily [2] | 5 mg once daily [1] | Standard dosing [3] |
| <30 mL/min (moderate-severe) | 2.5 mg once daily [2] | 2.5 mg once daily [1] | 25% of usual dose [3] |
| Dialysis patients | 2.5 mg on dialysis days [2] | 2.5 mg on dialysis days [1] | 1.25 mg once daily [3] |
For patients with hypertension and renal impairment (creatinine clearance >40 mL/min), usual regimens may be followed, but in patients with worse impairment, 25% of the usual dose of ramipril is expected to produce full therapeutic levels. 3
The usual dose of enalapril is recommended for patients with creatinine clearance >30 mL/min (serum creatinine up to approximately 3 mg/dL). 1
Dosage adjustment for lisinopril is necessary only when creatinine clearance is less than 30 mL/min. 9
In patients with hypertension associated with impaired renal function (GFR ≤60 ml/min), the starting dose should be 2.5 mg in patients with GFR <30 ml/min and 5 mg in all other patients, titrated to a maximum of 40 mg daily. 10
Monitoring Requirements
Check serum potassium and creatinine within 1–2 weeks of initiating an ACE inhibitor, with each dose increase, and at least yearly, especially in older adults with diabetes or renal impairment. 4
One RCT found that moderate doses of ACE inhibitors (captopril 75 mg/day, enalapril 10 mg/day, or lisinopril 10 mg/day) are significantly associated with the development of hyperkalemia. 4
A rise in serum creatinine of up to 20% after initiating an ACE inhibitor is acceptable and does not indicate progressive renal damage. 8
Older adults are more susceptible to reductions in renal function related to ACE inhibitors, requiring vigilant monitoring. 4
Concomitant Diuretic Use
If the patient is currently on a diuretic, reduce or discontinue the diuretic for 2–3 days before starting an ACE inhibitor, or use a lower initial ACE inhibitor dose (lisinopril 5 mg, enalapril 2.5 mg, ramipril 1.25 mg) under medical supervision for at least 2 hours. 1, 2, 3
In patients who are currently being treated with a diuretic, symptomatic hypotension may occur following the initial dose of enalapril; if the diuretic cannot be discontinued, an initial dose of 2.5 mg should be used under medical supervision for at least two hours and until blood pressure has stabilized for at least an additional hour. 1
The recommended starting dose in adult patients with hypertension taking diuretics is lisinopril 5 mg once per day. 2
After the initial dose of ramipril, observe the patient under medical supervision for at least two hours and until blood pressure has stabilized for at least an additional hour; if possible, reduce the dose of any concomitant diuretic. 3
Critical Monitoring and Safety Considerations
Concomitant administration of ACE inhibitors with potassium supplements, potassium salt substitutes, or potassium-sparing diuretics can lead to increases of serum potassium and should be avoided or monitored closely. 3, 1
ACE inhibitors should not be initiated in any patient with a history of angioedema, which occurs in fewer than 1% of patients but is more frequent in Black patients and may be life-threatening. 4
Although ARBs may be considered as alternative therapy for patients who developed angioedema with an ACE inhibitor, extreme caution is advised because some patients develop angioedema with ARBs as well. 4
Persistent dry cough occurs in up to 50% of patients (higher in Chinese patients) and usually appears within the first months of therapy; if the cough is not severe, encourage patients to continue taking the ACE inhibitor because of long-term benefits. 4