ALDACTONE

AbsorptionThe mean time to reach peak plasma concentration of spironolactone and the active metabolite, canrenone, in healthy volunteers is 2.6 and 4.3 hours, respectively.

Effect of foodFood increased the bioavailability of spironolactone (as measured by AUC) by approximately 95.4%. Patients should establish a routine pattern for taking ALDACTONE with regard to meals [see Dosage and Administration (2.1) ] .

DistributionSpironolactone and its metabolites are more than 90% bound to plasma pro...

14.1 Heart Failure The Randomized Aldactone Evaluation Study (RALES) was a placebo controlled, double-blind study of the effect of spironolactone on mortality in patients with highly symptomatic heart failure and reduced ejection fraction. To be eligible to participate patients had to have an ejection fraction of ≤ 35%, NYHA class III–IV symptoms, and a history of NYHA class IV symptoms within the last 6 months before enrollment. Patients with a baseline serum creatinine of >2.5 mg/dL or a recent increase of 25% or with a baseline serum potassium of >5.0 mEq/L were excluded. Follow-up visits a...

The following clinically significant adverse reactions are described elsewhere in the labeling:

• Hyperkalemia [see Warnings and Precautions (5.1) ]
• Hypotension and Worsening Renal Function [see Warnings and Precautions (5.2) ]
• Electrolyte and Metabolic Abnormalities [see Warnings and Precautions (5.3) ]
• Gynecomastia [see Warnings and Precautions (5.4 ]
• Impaired neurological function/ coma in patients with hepatic impairment, cirrhosis and ascites [see Use in Specific Populations (8.7) ]...

ALDACTONE is contraindicated in the patients with:

• Hyperkalemia
• Addison's disease
• Concomitant use of eplerenone ALDACTONE is contraindicated in patients with ( 4 ): ▪ Hyperkalemia ▪ Addison's disease ▪ Concomitant use of eplerenone

• Hyperkalemia: Monitor serum potassium within one week of initiation and regularly thereafter ( 5.1 ).
• Hypotension and Worsening Renal Function: Monitor volume status and renal function periodically ( 5.2 ).
• Electrolyte and Metabolic Abnormalities: Monitor serum electrolytes, uric acid and blood glucose periodically ( 5.3 ).
• Gynecomastia: ALDACTONE can cause gynecomastia ( 5.4 ). 5.1 Hyperkalemia ALDACTONE can cause hyperkalemia. This risk is increased by impaired renal function or concom...

7 DRUG INTERACTIONS

• Agents increasing serum potassium: Concomitant administration can lead to hyperkalemia ( 5.1 , 7.1 ).
• Lithium: Increased risk of lithium toxicity ( 7.2 ).
• NSAIDs: May reduce the diuretic, natriuretic and antihypertensive effect of ALDACTONE ( 7.3 ).
• Digoxin: ALDACTONE can interfere with radioimmunologic assays of digoxin exposure ( 7.4 ).
• Cholestyramine: Hyperkalemic ...