How to manage hyperkalemia risk in a patient taking Zytiga (abiraterone), Prednisone, and Lisinopril (ACE inhibitor)/HCTZ (Hydrochlorothiazide)?

From the Guidelines

To manage hyperkalemia risk in a patient taking Zytiga (abiraterone), Prednisone, and Lisinopril/HCTZ, it is crucial to monitor serum potassium levels frequently and consider medication adjustments, prioritizing the patient's morbidity, mortality, and quality of life. The most direct approach is to monitor serum potassium levels frequently, particularly during the first month of treatment and after any dose changes. I recommend checking potassium levels weekly for the first month, then monthly thereafter, as suggested by the expert consensus document on the management of hyperkalaemia in patients with cardiovascular disease treated with renin angiotensin aldosterone system inhibitors 1. The combination presents significant risk because abiraterone can increase mineralocorticoid levels leading to potassium retention, while ACE inhibitors like Lisinopril block aldosterone production, further increasing potassium levels. Although Prednisone and HCTZ both promote potassium excretion, they may not fully counteract this effect. If potassium levels exceed 5.0 mEq/L, consider reducing the Lisinopril dose or switching to an angiotensin receptor blocker (ARB) which may have less impact on potassium, as per the guidelines for managing hyperkalaemia in patients with cardiovascular disease treated with RAAS inhibitors 1. Ensure the patient maintains the standard Prednisone dosing (typically 5 mg twice daily) prescribed with Zytiga, as this helps mitigate mineralocorticoid excess, as noted in the study on castration-resistant prostate cancer: aua guideline amendment 2015 1. Dietary counseling to limit high-potassium foods is also important, and patients should be educated about symptoms of hyperkalemia including muscle weakness, palpitations, and numbness, and instructed to seek immediate medical attention if these occur. In cases of persistent hyperkalemia despite these measures, a nephrologist consultation may be necessary, and the use of potassium binders such as patiromer sorbitex calcium (PSC) or sodium zirconium cyclosilicate (SZC) can be considered to manage hyperkalaemia, as recommended by the expert consensus document 1.

From the FDA Drug Label

1. 1 Hypokalemia, Fluid Retention, and Cardiovascular Adverse Reactions due to Mineralocorticoid Excess Abiraterone acetate may cause hypertension, hypokalemia, and fluid retention as a consequence of increased mineralocorticoid levels resulting from CYP17 inhibition Monitor patients for hypertension, hypokalemia, and fluid retention at least once a month. Control hypertension and correct hypokalemia before and during treatment with abiraterone acetate

The patient is taking Lisinopril (an ACE inhibitor) which can increase the risk of hyperkalemia. However, Abiraterone can cause hypokalemia. To manage the risk of hyperkalemia in this patient, it is essential to:

• Monitor potassium levels regularly
• Adjust the dose of Lisinopril as needed to minimize the risk of hyperkalemia
• Control hypertension and correct hypokalemia before and during treatment with Abiraterone
• Consider the use of HCTZ (a thiazide diuretic) to help manage hypokalemia and fluid retention 2

From the Research

Managing Hyperkalemia Risk

To manage hyperkalemia risk in a patient taking Zytiga (abiraterone), Prednisone, and Lisinopril (ACE inhibitor)/HCTZ (Hydrochlorothiazide), consider the following:

• Monitor potassium levels regularly, as ACE inhibitors like Lisinopril can increase potassium levels 3
• Be aware that the use of abiraterone and prednisolone may have adverse effects such as hypertension, which can be managed with antihypertensive medications 4, 5
• Consider alternative antihypertensive medications that may have a lower risk of hyperkalemia, such as candesartan cilexetil/HCTZ, which has been shown to be better tolerated than Lisinopril/HCTZ 3

Patient-Specific Factors

When managing hyperkalemia risk, consider the following patient-specific factors:

• Age: older patients may be more susceptible to hyperkalemia due to decreased renal function 6
• Comorbidities: patients with cardiovascular disease or renal impairment may be more at risk for hyperkalemia 6
• Medication history: patients taking other medications that can increase potassium levels, such as potassium-sparing diuretics, may be at higher risk for hyperkalemia

Treatment Adjustments

If hyperkalemia occurs, consider the following treatment adjustments:

• Discontinue or reduce the dose of Lisinopril, or switch to a different antihypertensive medication 3
• Monitor potassium levels closely and adjust treatment as needed
• Consider adding a potassium-lowering medication, such as a loop diuretic, if necessary 7