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 class for managing heart failure and hypertension, with common examples including lisinopril, enalapril, ramipril, and captopril, and their use should be guided by the most recent evidence to minimize morbidity, mortality, and improve quality of life. The starting doses and maximum doses for ACE inhibitors vary by specific medication, as outlined in the guidelines 1, with examples including lisinopril (starting dose 2.5 to 5 mg once daily, maximum 20 to 40 mg once daily), enalapril (starting dose 2.5 mg twice daily, maximum 10 to 20 mg twice daily), and ramipril (starting dose 1.25 to 2.5 mg once daily, maximum 10 mg once daily). Dose adjustments are necessary for several factors including:

• Renal impairment, which requires lower doses to avoid exacerbating kidney function decline
• Elderly patients, who should start at lower doses due to potential increased sensitivity to the medication
• Blood pressure response, as the goal is to achieve optimal blood pressure control without causing hypotension
• Heart failure symptoms, as the dose may need to be adjusted based on the patient's clinical response Contraindications for ACE inhibitors include:
• Pregnancy, due to the potential for fetal harm
• History of angioedema, as ACE inhibitors can cause this rare but serious side effect
• Bilateral renal artery stenosis, because ACE inhibitors can worsen renal function in this setting
• Hyperkalemia, as ACE inhibitors can increase potassium levels
• Concomitant use with aliskiren in diabetic patients, due to increased risk of hyperkalemia and acute kidney injury Common side effects of ACE inhibitors include:
• Dry cough, affecting up to 20% of patients
• Hypotension, particularly first-dose hypotension
• Hyperkalemia
• Acute kidney injury, especially in patients with pre-existing renal issues
• Angioedema, a rare but potentially life-threatening side effect
• Taste disturbances The mechanism of action of ACE inhibitors involves blocking the conversion of angiotensin I to angiotensin II, which reduces vasoconstriction and aldosterone secretion, thereby lowering blood pressure and decreasing cardiac workload 1. Regular monitoring of blood pressure, renal function, and potassium levels is essential when initiating ACE inhibitor therapy and after dose adjustments to minimize the risk of adverse effects and ensure optimal therapeutic benefit 1. The use of ACE inhibitors should be guided by the most recent clinical guidelines, which recommend their use for patients with heart failure with reduced ejection fraction to reduce morbidity and mortality, with careful consideration of potential side effects and contraindications.

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 a day 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 medications used to treat hypertension and congestive heart failure 4, 5
• They work by blocking the action of angiotensin-converting enzyme, a substance that constricts blood vessels and increases blood pressure

Starting Dose and Maximum Dose

• The starting dose and maximum dose of ACE inhibitors vary depending on the specific medication and the patient's condition 6, 7
• For example, the starting dose of lisinopril is typically 5-10 mg once daily, with a maximum dose of 40 mg once daily 6
• The starting dose of enalapril is typically 2.5-5 mg once daily, with a maximum dose of 40 mg once daily 6

Adjustment of Dose

• The dose of ACE inhibitors may need to be adjusted based on the patient's response to the medication and the presence of any side effects 4, 8
• For example, the dose may need to be reduced in patients with renal impairment or increased in patients who are not responding to the initial dose 6

Common Contraindications

• ACE inhibitors are contraindicated in patients with a history of angioedema or hypersensitivity to the medication 4, 8
• They are also contraindicated in patients with bilateral renal artery stenosis or unilateral renal artery stenosis in a solitary kidney 5

Common Side Effects

• Common side effects of ACE inhibitors include cough, dizziness, and headache 4, 8
• Less common side effects include angioedema, hyperkalemia, and renal impairment 4, 5
• The incidence of side effects may vary depending on the specific medication and the patient's condition 6, 7