Topic Discussion: Zytiga (Abiraterone) induced hypernatremia, and HTN

Zytiga (Abiraterone) is a hormonal chemotherapy agent used to treat prostate cancer. It selectively and irreversibly inhibits CYP17 (17 alpha-hydroxylase/C17,20-lyase), an enzyme required for androgen biosynthesis which is expressed in testicular, adrenal, and prostatic tumor tissues. Inhibits the formation of the testosterone precursors dehydroepiandrosterone (DHEA) and androstenedione.

Interestingly. it has a high rate of hypernatremia as a known renal complication. In several studies, hypernatremia (33%), hypokalemia (17% to 30%) were reported as known complications. Why? It is postulated that it can increase mineralocorticoids due to CYP17 inhibition may result in hypertension, hypokalemia, and fluid retention (including grade 3 and 4 events) and perhaps some component of hypernatremia as well- almost like a Cushing's state. Per package insert, concomitant administration with corticosteroids reduces the incidence and severity of these adverse events.

In the LATITUDE trial, which used prednisone 5 mg daily in combination with 1000 mg abiraterone acetate daily, grades 3-4 hypokalemia were detected in 10% of patients on the zytiga arm and 1% of patients on the placebo arm, grades 3-4 hypertension were observed in 20% of patients on the zytiga arm and 10% of patients on the placebo arm. Grades 3-4 fluid retention occurred in 1% of patients each arm.

It is recommended that patients get monitored for hypertension, hypokalemia, and fluid retention at least once a month. Treatment of hypertension is recommended, choice of drug is not defined.

This is an interesting toxicity that as nephrologist seeing prostate cancer with CKD and perhaps new onset hypertension, hypokalemia or hypernatremia should consider in the differential diagnosis.