What is the appropriate dosing of spironolactone (aldosterone antagonist)?

From the Guidelines

Spironolactone should be started at a dose of 100 mg and increased to 400 mg as needed, particularly in patients with moderate ascites due to cirrhosis, as recommended by the most recent guidelines. This dosing strategy is based on the 2021 guidelines on the management of ascites in cirrhosis published in the journal Gut 1. The guidelines suggest that in patients with the first presentation of moderate ascites, spironolactone monotherapy is reasonable, starting at 100 mg and increasing to 400 mg as needed.

• Key considerations for dosing include:
  • Starting dose: 100 mg
  • Maximum dose: 400 mg
  • Indication: Moderate ascites due to cirrhosis
  • Monitoring: Patients should be monitored for adverse events, and diuretic discontinuation or dose reduction may be necessary in almost half of those with adverse events, as noted in the guidelines 1.
• It is essential to monitor patients initiating diuretics for adverse events, as stated in the guidelines, and to manage hypovolaemic hyponatraemia by discontinuing diuretics and expanding plasma volume with normal saline 1.
• The guidelines also recommend combination therapy with spironolactone and furosemide for patients with recurrent severe ascites who require faster diuresis, such as hospitalized patients 1.
• In clinical practice, it is crucial to consider the individual patient's response to treatment and adjust the dose accordingly, while also monitoring for potential side effects and adjusting the treatment plan as needed.

From the FDA Drug Label

2 DOSAGE AND ADMINISTRATION

Dosage and administration 2.1 General Considerations Spironolactone tablets can be taken with or without food, but should be taken consistently with respect to food [see Clinical Pharmacology (12.3)] . 2.2 Treatment of Heart Failure In patients with serum potassium ≤ 5.0 mEq/L and eGFR > 50 mL/min/1. 73 m 2, initiate treatment at 25 mg once daily. Patients who tolerate 25 mg once daily may have their dosage increased to 50 mg once daily as clinically indicated. Patients who develop hyperkalemia on 25 mg once daily may have their dosage reduced to 25 mg every other day [see Warnings and Precautions (5.1)] . In patients with an eGFR between 30 and 50 mL/min/1. 73 m 2, consider initiating therapy at 25 mg every other day because of the risk of hyperkalemia [see Use in Specific Populations (8.6)]. 2. 3 Treatment of Essential Hypertension The recommended initial daily dose is 25 mg to 100 mg of spironolactone tablets administered in either single or divided doses is recommended. Dosage can be titrated at two-week intervals. Doses greater than 100 mg/day generally do not provide additional reductions in blood pressure. 2. 4 Treatment of Edema In patients with cirrhosis, initiate therapy in a hospital setting and titrate slowly [see Use in Specific Populations (8. 7)] . The recommended initial daily dosage is 100 mg of spironolactone tablets administered in either single or divided doses, but may range from 25 mg to 200 mg daily. When given as the sole agent for diuresis, administer for at least five days before increasing dose to obtain desired effect. 2. 5 Treatment of Primary Hyperaldosteronism Administer spironolactone tablets in doses of 100 mg to 400 mg daily in preparation for surgery. For patients who are considered unsuitable for surgery, spironolactone tablets can be used as long-term maintenance therapy at the lowest effective dosage determined for the individual patient.

The dosing of spironolactone varies depending on the condition being treated.

• Heart Failure: 25 mg once daily, potentially increasing to 50 mg once daily as clinically indicated, or reducing to 25 mg every other day if hyperkalemia develops.
• Essential Hypertension: 25 mg to 100 mg daily, with dosage titration at two-week intervals.
• Edema: 100 mg daily, ranging from 25 mg to 200 mg daily, with slow titration in patients with cirrhosis.
• Primary Hyperaldosteronism: 100 mg to 400 mg daily for preparation for surgery or long-term maintenance therapy at the lowest effective dosage. 2

From the Research

Dosing of Spironolactone

• The dosing of spironolactone is crucial in patients with severe chronic heart failure, as it can affect serum electrolytes and renal function tests 3.
• A study found that a single daily dose of 25 mg of spironolactone caused a significant elevation of serum potassium level, but this elevation was still within clinically accepted ranges when low-dose spironolactone was used and renal function was intact 3.
• However, another study found that dosing of spironolactone more than 25 mg per day was a risk factor for hyperkalemia in adult patients taking spironolactone and angiotensin converting enzyme inhibitors or angiotensin receptor blockers 4.
• The prevalence of hyperkalemia in adult patients taking spironolactone and ACEIs or ARBs was found to be 11.2%, with risk factors including chronic kidney disease, high serum potassium, and high spironolactone use 4.
• A systematic review and meta-analysis found that spironolactone reduced blood pressure and urinary albumin, improved fibrosis and inflammation, but slightly increased serum creatinine and glycosylated haemoglobin in patients with hypertension and diabetes 5.
• A study on the long-term effects of spironolactone on kidney function and hyperkalemia-associated hospitalization in patients with chronic kidney disease found that spironolactone users had a lower incidence rate for end-stage renal disease, but a higher incidence rate for hyperkalemia-associated hospitalization 6.
• Another study found that the addition of spironolactone to loop diuretics in patients with heart failure was associated with a higher risk of hyperkalemia and acute kidney injury, which must be weighed against the potential benefits of spironolactone 7.

Key Considerations

• Serum potassium levels should be closely monitored in patients on spironolactone therapy, especially those who use ACEIs and ARBs in addition 3.
• Renal function tests, including serum creatinine and blood urea, should also be closely monitored in patients on spironolactone therapy 3.
• The risk of hyperkalemia and acute kidney injury should be considered when initiating spironolactone therapy in patients with heart failure 7.