Pharmacological profile, clinical efficacy, and safety of esaxerenone (Minnebro® tablets 1.25 mg, 2.5 mg, 5 mg)

Abstract

Esaxerenone is a novel non-steroidal mineralocorticoid receptor antagonisit (MR blocker), whose unique binding to the MR-ligand domain yields a stronger MR antagonistic effect and higher selectivity than existing MR antagonisits. Esaxerenone was approved for the treatment of hypertension in Japan in January 2019. Esaxerenone suppresses the reduction of urinary Na+/K+ ratio in adrenalectomized rats and blood pressure increase, proteinuria, and renal tissue lesions in salt-sensitive hypertensive rats—all in a dose-dependent manner. Esaxerenone is rapidly absorbed and reaches intracellular targets because of its high membrane permeability, exhibits high bioavailability with small interindividual exposure variation, and is metabolized via several pathways (e.g., oxidation, glucuronidation, and hydrolysis), which is associated with low drug–drug interaction risk. As esaxerenone is slightly excreted into urine, its exposure is similar between elderly and non-elderly patients, and between patients with normal and moderately deteriorated renal function. Given its 19-hour half-life, once-daily administration would have a sustainable antihyper tensive effect. The ESAX-HTN phase 3 study demonstrated the non-i nferi ori ty of esaxerenone’s antihypertensive effect versus that of eplerenone in essential hypertension. Another study showed a stable antihypertensive effect for 52 weeks as monotherapy or combination therapy. In hypertensive patients with moderate impairment or both type 2 diabetes and albuminuria treated with a renin–angiotensin system inhibitor, esaxerenone elicited a stable antihypertensive effect and manageable hyperkalemia incidence with titration from a low dose and monitoring including serum potassium. Thus, with careful monitoring of serum potassium, esaxerenone can be administered to patients with moderate renal impairment or both diabetes and albuminuria.