Spironolactone

ALDACTONE is an aldosterone antagonist indicated for: • The treatment of NYHA Class III–IV heart failure and reduced ejection fraction to increase survival, manage edema, and to reduce the need for hospitalization for heart failure. • Use as an add-on therapy for the treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. • The management of edema in adult patients who are cirrhotic when edema is not responsive to fluid and sodium restrictions and in the setting of nephrotic syndrome when treatment of the underlying disease, restriction of fluid and sodium intake, and the use of other diuretics produce an inadequate response.

Spironolactone and its active metabolites are specific pharmacologic antagonists of aldosterone, acting primarily through competitive binding of receptors at the aldosterone-dependent sodium-potassium exchange site in the distal convoluted renal tubule. Spironolactone causes increased amounts of sodium and water to be excreted, while potassium is retained. Spironolactone acts both as a diuretic and as an antihypertensive drug by this mechanism. It may be given alone or with other diuretic agents that act more proximally in the renal tubule.

• Heart Failure: Initiate treatment at 25 mg once daily. • Hypertension: Initiate treatment at 25 to 100 mg daily in either single or divided doses. • Edema: Initiate therapy in a hospital setting and titrate slowly. The recommended initial daily dose is 100 mg in single or divided doses. • Primary hyperaldosteronism: Initiate treatment at 100 to 400 mg in preparation for surgery. In patients unsuitable for surgery use the lowest effective dosage determined for the individual patient.

ALDACTONE is contraindicated in the patients with: • Hyperkalemia • Addison's disease • Concomitant use of eplerenone ALDACTONE is contraindicated in patients with: • Hyperkalemia • Addison's disease • Concomitant use of eplerenone

• Hyperkalemia: Monitor serum potassium within one week of initiation and regularly thereafter. • Hypotension and Worsening Renal Function: Monitor volume status and renal function periodically. • Electrolyte and Metabolic Abnormalities: Monitor serum electrolytes, uric acid and blood glucose periodically. • Gynecomastia: ALDACTONE can cause gynecomastia.

The following clinically significant adverse reactions are described elsewhere in the labeling: • Hyperkalemia • Hypotension and Worsening Renal Function • Electrolyte and Metabolic Abnormalities • Gynecomastia • Impaired neurological function/ coma in patients with hepatic impairment, cirrhosis and ascites The following adverse reactions associated with the use of spironolactone were identified in clinical trials or postmarketing reports. Because these reactions were reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency, reliably, or to establish a causal relationship to drug exposure. Digestive: Gastric bleeding, ulceration, gastritis, diarrhea and cramping, nausea, vomiting. Reproductive: Decreased libido, inability to achieve or maintain erection, irregular menses or amenorrhea, postmenopausal bleeding, breast and nipple pain.

• Agents increasing serum potassium: Concomitant administration can lead to hyperkalemia. • Lithium: Increased risk of lithium toxicity. • NSAIDs: May reduce the diuretic, natriuretic and antihypertensive effect of ALDACTONE. • Digoxin: ALDACTONE can interfere with radioimmunologic assays of digoxin exposure. • Cholestyramine: Hyperkalemic metabolic acidosis has been reported with concomitant use. • Acetylsalicylic Acid (ASA): ASA may reduce the efficacy of ALDACTONE. • Abiraterone: May increase prostate-specific antigen (PSA) levels. • Mitotane: Avoid concomitant use of ALDACTONE and mitotane.

Store below 77°F (25°C).