What are the starting and maximum doses of Angiotensin-Converting Enzyme (ACE) inhibitors, the causes for dose adjustment, common contraindications, and side effects?

From the Guidelines

Angiotensin-converting enzyme (ACE) inhibitors are a crucial medication for patients with heart failure, with common ACE inhibitors including lisinopril, enalapril, ramipril, and captopril, and their use is recommended to reduce morbidity and mortality in patients with heart failure with reduced ejection fraction (HFrEF) 1.

Starting Dose and Maximum Dose

The starting dose and maximum dose of ACE inhibitors vary depending on the specific medication, but common starting doses include:

• Lisinopril: 2.5 to 5 mg once daily, with a maximum dose of 20 to 40 mg once daily 1
• Enalapril: 2.5 mg twice daily, with a maximum dose of 10 to 20 mg twice daily 1
• Ramipril: 1.25 to 2.5 mg once daily, with a maximum dose of 10 mg once daily 1
• Captopril: 6.25 mg three times daily, with a maximum dose of 50 mg three times daily 1

Cause of Adjustment of the Dose

Dose adjustments are necessary for:

• Renal impairment: reduce dose
• Elderly patients: start with a lower dose
• Based on blood pressure response or heart failure symptoms: titrate upward every 2-4 weeks until target blood pressure or symptom control is achieved

Common Contraindications

Contraindications include:

• Pregnancy: can cause fetal harm
• History of angioedema
• Bilateral renal artery stenosis
• Hyperkalemia
• Allergy to ACE inhibitors

Common Side Effects

Common side effects include:

• Dry cough: 10-20% of patients
• Hypotension: especially first-dose
• Hyperkalemia
• Acute kidney injury
• Angioedema
• Taste disturbances
• Rarely neutropenia

Monitoring

Blood pressure, renal function, and potassium levels should be monitored regularly, especially after initiation and dose increases 1. Some key points to consider when starting ACE inhibitors include:

• Review the need for and dose of diuretics and vasodilators
• Avoid excessive diuresis before treatment
• Start with a low dose and build up to recommended maintenance dosages
• Check blood pressure, renal function, and electrolytes 12 weeks after each dose increment, at 3 months, and subsequently at 6 monthly intervals 1.

From the FDA Drug Label

DOSAGE & ADMINISTRATION 2. 1 Hypertension Initial Therapy in adults: The recommended initial dose is 10 mg once a day. Dosage should be adjusted according to blood pressure response. The usual dosage range is 20 mg to 40 mg per day administered in a single daily dose. 2. 2 Heart Failure The recommended starting dose for lisinopril tablets, when used with diuretics and (usually) digitalis as adjunctive therapy for systolic heart failure, is 5 mg once daily. 2. 4 Dose in Patients with Renal Impairment No dose adjustment of lisinopril tablets is required in patients with creatinine clearance > 30 mL/min. The dosage may be titrated upward until blood pressure is controlled or to a maximum of 40 mg daily.

ACE Medication Summary

• Starting Dose:
  • Lisinopril: 10 mg once daily for hypertension, 5 mg once daily for heart failure
  • Enalapril: 5 mg once daily
• Maximum Dose:
  • Lisinopril: 40 mg once daily
  • Enalapril: 40 mg daily
• Dose Adjustment:
  • Lisinopril: adjusted according to blood pressure response
  • Enalapril: titrated upward until blood pressure is controlled
• Common Contraindications:
  • Lisinopril: not recommended in pediatric patients < 6 years or in pediatric patients with glomerular filtration rate < 30 mL/min/1.73m2
  • Enalapril: not recommended in neonates and in pediatric patients with glomerular filtration rate <30 mL/min/1. 73 m 2
• Common Side Effects:
  • Lisinopril: hypotension, renal impairment
  • Enalapril: hypotension, renal impairment, hyperkalemia 2 3

From the Research

ACE Medication Overview

• ACE inhibitors are a class of drugs used to treat hypertension and heart failure by inhibiting the renin-angiotensin-aldosterone system 4.
• They cause vasodilation, mild natriuresis, and reduce blood pressure without affecting heart rate and contractility 4.

Starting Dose and Maximum Dose

• The starting dose and maximum dose of ACE inhibitors vary depending on the specific medication and patient condition.
• For example, captopril has a flat dose response curve and should be given at a dose not exceeding 150 mg/day 4.
• Enalapril is a promising ACE inhibitor with a prolonged action of at least 24 hours 4.

Adjustment of Dose

• The dose of ACE inhibitors may need to be adjusted based on patient response and tolerability.
• Factors that may require dose adjustment include renal function, sodium depletion, and collagen disease 4.
• The dose should be titrated to achieve optimal blood pressure control while minimizing side effects 5.

Common Contraindications

• ACE inhibitors are contraindicated in pregnancy and hyperkalemic syndromes 4.
• They should be used with caution in patients with collagen disease, severe bilateral renal artery stenosis, and severe sodium depletion 4.

Common Side Effects

• Common side effects of ACE inhibitors include cough, skin rash, fever, taste disturbances, proteinuria, and neutropenia 4, 5.
• Hyperkalemia is a frequent occurrence due to the effect of ACE inhibitors on plasma aldosterone 5.
• Angioedema is a rare but potentially life-threatening side effect of ACE inhibitors 6, 7.