SAT-417 - Reduced Efficacy of Eplerenone in Primary Hyperaldosteronism with Concomitant Use of Primidone

Background:

Medical treatment for primary hyperaldosteronism with bilateral disease is mineralocorticoid receptor antagonists (MRA). Eplerenone, an off-label drug, is used to treat primary hyperaldosteronism in patients who cannot tolerate standard therapy spironolactone due to its side effects like gynecomastia. Primidone, a medication used for essential tremors, is a potent cytochrome 450 inducer. This enzyme induction accelerates the metabolism of other medications, including eplerenone, often reducing their effectiveness.

Clinical

Case:

A 67-year-old male with confirmed bilateral primary hyperaldosteronism was being treated with Eplerenone. He was previously diagnosed with essential tremors many years ago and has been on Primidone since. Despite being on adequate doses (150 mg twice daily) of eplerenone, the patient continued to have persistent hypertension and hypokalemia. He was being considered for switching to Finerenone due to suboptimal response with eplerenone.

Patient was subsequently admitted to the hospital for hypertensive emergency while still on eplerenone and primidone. Identification of the drug interaction between eplerenone and primidone led to discontinuation of primidone. This resulted in improvement in blood pressure and normalization of potassium levels. The patient, previously on five antihypertensives, was thereafter required only one antihypertensive medication. Potassium supplements were also successfully discontinued.

Discussion:

Primidone is a potent inducer of multiple CYP450 enzymes, notably CYP3A4. Eplerenone is cleared predominantly by CYP3A4 metabolism, resulting in increased clearance and reduced bioavailability of eplerenone when used with primidone.

Conclusion:

This case highlights the importance of being aware of CYP3A4-inducing medications in patients on mineralocorticoid receptor antagonists, especially when patients have exhibited unsatisfactory clinical outcomes.

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