Is lisinopril (angiotensin-converting enzyme inhibitor) associated with hyponatremia (low sodium levels)?

From the Guidelines

Lisinopril is not directly associated with hyponatremia, but it can contribute to the development of hyponatremia in certain patients, particularly those with heart failure or kidney disease, due to its effects on the renin-angiotensin-aldosterone system and water balance in the body. As an angiotensin-converting enzyme (ACE) inhibitor, lisinopril works by blocking the conversion of angiotensin I to angiotensin II, which can affect sodium and water balance in the body. The mechanism involves increased antidiuretic hormone (ADH) levels and impaired water excretion, leading to dilutional hyponatremia in some patients. Risk factors for developing hyponatremia while on lisinopril include advanced age, female gender, low body weight, concomitant use of diuretics, kidney disease, and heart failure. Symptoms of hyponatremia may include headache, confusion, nausea, muscle cramps, seizures, and in severe cases, coma. If a patient on lisinopril develops these symptoms, sodium levels should be checked promptly. Management typically involves sodium level monitoring, possible dose adjustment or medication change, and in severe cases, fluid restriction or sodium supplementation. Patients taking lisinopril should be advised to report unusual symptoms and have regular electrolyte monitoring, especially when starting therapy or changing dosage 1.

Some key points to consider when managing hyponatremia in patients taking lisinopril include:

• Monitoring sodium levels regularly, especially in high-risk patients
• Adjusting the dose of lisinopril or switching to a different medication if necessary
• Restricting fluid intake in patients with hypervolemic hyponatremia
• Considering the use of vasopressin antagonists, such as tolvaptan, in patients with severe hyponatremia and cognitive symptoms
• Assessing for alternative causes of hyponatremia, such as syndrome of inappropriate antidiuretic hormone, hypothyroidism, and hypoaldosteronism.

It is essential to note that the evidence for the association between lisinopril and hyponatremia is not strong, and the majority of the studies focus on the management of hyponatremia in patients with heart failure or cirrhosis, rather than the direct effects of lisinopril on sodium levels 1. However, as a precautionary measure, patients taking lisinopril should be closely monitored for signs of hyponatremia, and their sodium levels should be checked regularly.

From the FDA Drug Label

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. The recommended starting dose in these patients with hyponatremia (serum sodium < 130 mEq/L) is 2. 5 mg once daily.

Lisinopril is not directly associated with causing hyponatremia. However, the dose of lisinopril needs to be adjusted in patients with hyponatremia, indicating that hyponatremia may be a consideration when using the medication. Key points:

• The dose of lisinopril is reduced in patients with hyponatremia.
• Lisinopril can be used in patients with hyponatremia, but with a lower starting dose of 2.5 mg once daily 2.

From the Research

Association between Lisinopril and Hyponatremia

• There is evidence to suggest that lisinopril, an angiotensin-converting enzyme inhibitor, may be associated with hyponatremia (low sodium levels) in some patients 3, 4.
• A case study published in 1990 reported a 63-year-old woman who developed severe hyponatremia after starting lisinopril therapy, with serum sodium levels dropping to 109 mmol/L 3.
• Another case report published in 1992 described a 63-year-old woman who presented with seizures, altered mental status, and a serum sodium of 101 mEq/L while being treated with lisinopril for hypertension 4.
• However, not all studies have found a direct link between lisinopril and hyponatremia, and the condition may be multifactorial in nature 5, 6.

Mechanisms and Treatment Options

• Hyponatremia in heart failure patients is often caused by the activation of neurohormonal systems, leading to a decrease in sodium levels 5, 6.
• Treatment options for hyponatremia in heart failure include water restriction, loop diuretics, and arginine vasopressin (AVP)-receptor antagonists, such as tolvaptan 7, 5, 6.
• Early administration of tolvaptan has been shown to be effective in treating hyponatremia in acutely decompensated heart failure patients, with a lower length of hospitalization and a higher increase in serum sodium levels 7.