Eplerenone

Indications

Eplerenone is used for: Hypertension, Heart failure, Congestive heart failure, Left ventricular dysfunction, Acute myocardial infarction

Adult Dose

Hypertension (HTN) Initial 50 mg PO qDay; may increase to 50 mg PO q12hr; may take up to four weeks for full therapeutic response; hyperkelemia may occur with doses >100 mg/day Heart Failure Post MI Initial 25 mg PO qDay; may titrate to maximum of 50 mg once daily within 4 weeks as tolerated Dose adjustments may be required based on potassium levels Hepatic Impairment Dose adjustment not necessary

Child Dose

Renal Dose

Renal Impairment Contraindicated if CrCl <50 mL/min or serum creatinine >2 mg/dL in males or >1.8 mg/dL in females

Administration

May be taken with or without food.

Contra Indications

For all patients: Serum potassium >5.5 mEq/L at initiation; CrCl ?30 mL/min; concomitant use of strong CYP3A4 inhibitors (e.g. ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir, nelfinavir). For patients treated for hypertension: Patients with type 2 DM with microalbuminuria; serum creatinine >2 mg/dL (male), or >1.8 mg/dL (female); CrCl <50 mL/min; concomitant use of potassium supplements or potassium-sparing diuretics (e.g. amiloride, spironolactone, or triamterene).

Precautions

Measure serum potassium levels before starting therapy, within the first wk, and periodically thereafter. Increased risk of hyperkalaemia in patients with impaired renal functions; diabetic patients with CHF post-MI (especially those with proteinuria); or concurrent use of agents affecting the rennin-angiotensin-aldosterone system. Safety and efficacy not established in patients with severe hepatic impairment; or paediatric patients <18 yr. Elderly. Pregnancy and lactation. Lactation: unknown if excreted into breast milk, discontinue drug or nursing

Pregnancy-Lactation

Pregnancy Available data from published case reports on eplerenone use during pregnancy are insufficient to establish a drug-associated risk of major birth defects, miscarriage, adverse maternal or fetal outcomes; in animal studies, no adverse developmental effects were observed when eplerenone was administered to pregnant rats and rabbits during organogenesis at exposures 32 and 31 times, respectively the human exposure at the 100 mg/day therapeutic dose Hypertension in pregnancy increases maternal risk for pre-eclampsia, gestational diabetes, premature delivery, and delivery complications (e.g., need for cesarean section, and post-partum hemorrhage); hypertension increases fetal risk for intrauterine growth restriction and intrauterine death; pregnant women with hypertension should be carefully monitored and managed accordingly Infertility Based on animal data, therapy may compromise male fertility; in mature rates, male fertility was decreased with eplerenone exposure at 17 times the 100 mg/day human therapeutic dose; reversibility of effect, not evaluated Lactation There are no human data available on whether eplerenone is present in human milk, or has effects on breastfed infants or on milk production; eplerenone was present in milk of lactating rats; when a drug is present in animal milk, it is likely that the drug will be present in human milk

Interactions

Concomitant use with CYP3A4 Inhibitors (e.g. ketoconazole, voriconazole, itraconazole, fluconazole, clarithromycin, diltiazem saquinavir, verpamil, ritonavir) may increase serum concentrations of Eplerenone. CYP3A4 inducers (e.g. rifampicin, carbamazepine, phenytoin, phenobarbital) may decrease Eplerenone efficacy. Eplerenone may enhance hyperkalaemic effect of ACE inhibitors, angiotensin II receptor blockers, potassium-sparing diuretics or potassium salts. Concomitant use with diazoxide, MAOIs, pentoxifylline, prostacyclin analogues may enhance hypotensive effect of antihypertensives. NSAIDs may possibly reduce the antihypertensive and/or diuretic effects of potassium-sparing diuretics and may increase risk of hyperkalaemia. Lithium toxicity has been reported when used with ACE inhibitors or diuretics; monitor lithium levels when used with Eplerenone.

Side Effects

Side effects of Eplerenone : 1-10% Hyperkalemia (2-10%), Increased risk of hyperkalemia with presence of renal dysfunction 1-3% Dizziness, Fatigue/malaise, Abdominal pain, Diarrhea, Albuminuria, Hypercholesterolemia, Hypertriglyceridemia, Cough <1% Abnormal vaginal bleeding, Gynecomastia, Mastodynia

Mode of Action

Aldosterone binds to mineralocorticoid receptors in both epithelial (e.g. kidney, GI tract) and nonepithelial (e.g. heart, blood vessels, brain) tissues; causing increases in blood pressure by inducing sodium reabsorption, vascular remodeling, water retention and possibly other mechanisms. Eplerenone is a relatively selective mineralocorticoid receptor antagonist, blocking binding of aldosterone and reducing blood pressure. Eplerenone also appears to have cardioprotective effect in patients with congestive heart failure (CHF) after myocardial infarction (MI).