依普利酮使用说明

Instructions for use, Generic name: eplerenone, Trade name: Planep, All names: eplerenone, Inspra, eplerenone, Planep.

Eplerenone is used in congestive heart failure after acute myocardial infarction and for the treatment of hypertension.

Usage and dosage of eplerenone: Common dosage for adults with congestive heart failure, initial dose: 25 mg, orally, once a day; and within 4 weeks, gradually increase to the target dose, subject to patient tolerance, target dose: 50 mg, orally, once a day.

Common doses of eplerenone for adults with hypertension: Eplerenone can be used alone or in combination with other antihypertensive drugs. Initial dose: 50 mg, taken orally, once a day. Maintenance dose: 50 mg, taken orally, 1-2 times a day. Maximum dose: 100 mg/day. Obvious antihypertensive effects appear within four weeks of medication. Patients whose blood pressure responds inadequately to the initial dose may be increased to 50 mg twice daily.

Adverse reactions of eplerenone

>10% Endocrinology and metabolism: hyperkalemia, hypertension, hypertriglyceridemia.

1%-10% Central nervous system: dizziness, fatigue.

Endocrinology and metabolism: hyponatremia, proteinuria, gynecomastia, hypercholesterolemia.

Gastrointestinal tract: diarrhea, abdominal pain.

Genitourinary system: abnormal vaginal bleeding, breast pain (males: ≤1%).

Renal: Increased serum creatinine (heart failure, post-myocardial infarction: 6%).

Respiratory system: Cough, flu-like symptoms.

<1% post-marketing or case reports: angioedema, increased blood urea nitrogen, increased liver enzymes, increased uric acid, rash.

Eplerenone contraindications: serum potassium >5.5meq/L at the beginning; CrCl (creatinine clearance rate) ≤30ml/min; concurrent use of strong CYP3A4 inhibitors (such as ketoconazole, itraconazole, nefazodone, ditroleandomycin, clarithromycin, ritonavir, nelfinavir). The following additional contraindications apply to patients with hypertension: type 2 diabetes mellitus (non-insulin-dependent, NIDDM) with microalbuminuria; serum creatinine >2.0 mg/dL in men or >1.8 mg/dL in women; CrCl <50 mL/min; concurrent use of potassium supplements or potassium-sparing diuretics (eg, amiloride, spironolactone, triantiline). In accordance with the Endocrine Society Clinical Practice Guidelines, use is contraindicated in patients with Addison's disease, hypersensitivity to eplerenone or any component of the formulation; initial serum potassium, severe hepatic impairment (Child-Pugh class C); clinically significant hyperkalemia; concurrent use with potassium supplementation or potassium-sparing diuretics. The following additional contraindications apply to patients with hypertension: serum creatinine >1.5 mg/dL [132 micromol/L] in men and >1.3 mg/dL [115 micromol/L] in women.

Precautions for eplerenone

Hyperkalemia: Hyperkalemia may occur; the risk of hyperkalemia is increased with renal impairment, proteinuria, diabetes mellitus, and in patients concurrently taking ACE (angiotensin-converting enzyme) inhibitors, angiotensin II inhibitors, NSAIDs, or moderate CYP3A inhibitors. Monitor closely for hyperkalemia; serum potassium increased dose-related during clinical trials. As hyperkalemia develops, dose reduction or treatment interruption may be necessary. If concomitant treatment with a moderate CYP3A4 inhibitor cannot be avoided, reduce the eplerenone dose. It is contraindicated in patients with potassium greater than 5.5 meq/L at the beginning of treatment.

Diabetes: Use with caution in patients with diabetes and post-myocardial infarction heart failure (especially those with proteinuria); the risk of hyperkalemia is increased.

Heart failure: When evaluating patients with heart failure to receive eplerenone treatment, eGFR (epidermal growth factor receptor) should be greater than 30ml/min/1.73m2 or creatinine should be less than or equal to 2.5mg/dL (men) or less than or equal to 2mg/dL (women) with no recent worsening, potassium less than 5meq/L and no history of severe hyperkalemia. If blood potassium levels are elevated, close monitoring and management are required. The manufacturer recommends that treatment should be discontinued if serum potassium is >6 meq/L. ACCF/AHA (American College of Cardiology Foundation) recommends that when serum potassium concentration is >5.5 meq/L or renal function worsens, discontinuation of the drug should be considered and the entire medical regimen should be carefully evaluated. Avoid conventional triple therapy and use a combination of ACE (angiotensin-converting enzyme) inhibitors, ARB (one of the first-line treatments for hypertension) and eplerenone. Instruct patients with heart failure to discontinue use during episodes of diarrhea or dehydration or when circulating diuretic therapy is interrupted.

Liver damage: Use with caution in patients with moderate to severe liver damage.

Kidney Impairment: As kidney function decreases, the risk of hyperkalemia increases. Use with caution in patients with mild renal impairment; it may be disabled depending on the indications and degree of damage.

Drug-Drug Interactions: Significant interactions may exist requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapies.

Potassium Supplements: Avoid potassium supplements, potassium-containing salt substitutes, potassium-rich diets, or other medications that may cause hyperkalemia (e.g., other potassium-sparing diuretics, nonsteroidal anti-inflammatory drugs). Concomitant use of potassium supplements or potassium-sparing diuretics is contraindicated in the treatment of hypertension.

Pregnancy: Untreated hypertension and heart failure are both associated with adverse pregnancy outcomes. The use of mineralocorticoid receptor antagonists is not recommended for the treatment of chronic isolated hypertension in pregnant women and should generally be avoided in women of reproductive potential.

Eplerenone Mechanism of Action: Eplerenone binds to the mineralocorticoid receptor, thereby blocking the binding of aldosterone, a component of the renin-angiotensin-aldosterone system (RAAS). Aldosterone synthesis occurs primarily in the adrenal gland and is regulated by multiple factors, including angiotensin II and non-RAAS mediators such as adrenocorticotropic hormone (ACTH) and potassium. Aldosterone binds to mineralocorticoid receptors in epithelial tissues (such as the kidneys) and non-epithelial tissues (such as the heart, blood vessels, and brain) and increases blood pressure by inducing sodium reabsorption and possibly other mechanisms.

Safety and efficacy of eplerenone: Eplerenone is a new type of selective aldosterone receptor antagonist. It was approved for clinical use by the State Food and Drug Administration in 2002. The pure product is a white or off-white crystal. It has a stronger antagonistic effect on aldosterone than spironolactone, and has extremely low affinity for androgen and progesterone receptors. It has few adverse reactions. It has definite efficacy in the treatment of hypertension, heart failure and myocardial infarction. It has fewer adverse reactions and good tolerance. It is a good alternative to spironolactone.

For severe hypertension that cannot be controlled by a combination of multiple antihypertensive drugs, the addition of eplerenone can significantly reduce blood pressure, especially the decrease in systolic blood pressure is more significant. Combined treatment with angiotensin-converting enzyme inhibitors (ACEI) and beta-blockers can improve patients' quality of life and reduce mortality in severe heart failure and myocardial infarction.

For the treatment of heart failure after acute myocardial infarction, combined use with standard treatment drugs can reduce the total mortality in the treatment group by 15% (P=0.008). Eplerenone and enalapril are equally effective in reversing left ventricular hypertrophy and hypertension. They have fewer cough side effects, and the combined application has more obvious effects and fewer adverse reactions. Except for the adverse reactions of increased blood potassium, other adverse reactions are no different from the placebo group, and there are almost no sex hormone-related side effects of spironolactone.

The FDA (U.S. Food and Drug Administration) has approved eplerenone for use in stable patients with left ventricular systolic dysfunction (ejection fraction <40%) and congestive heart failure after acute myocardial infarction (MI) to improve survival rates. Eplerenone is the first aldosterone receptor blocker approved for this indication. The FDA's approval was based on the results of the EPHESUS (Eplerenone Efficacy and Survival Study in Heart Failure After Acute Myocardial Infarction) trial. In patients with heart failure after myocardial infarction, adding standard treatment (ACE inhibitors and beta-blockers) reduced mortality by 15% compared with placebo and standard treatment.