Aldactone (Page 4 of 4)

14 CLINICAL STUDIES

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 and laboratory measurements (including serum potassium and creatinine) were performed every four weeks for the first 12 weeks, then every 3 months for the first year, and then every 6 months thereafter.

The initial dose of spironolactone was 25 mg once daily. Patients who were intolerant of the initial dosage regimen had their dose decreased to one 25 mg tablet every other day at one to four weeks. Patients who were tolerant of one tablet daily at 8 weeks may have had their dose increased to 50 mg daily at the discretion of the investigator. The mean daily dose at study end for patients randomized to spironolactone was 26 mg.

1663 patients were randomized 1:1 to spironolactone or placebo. 87% of patients were white, 7% black, 2% Asian. 73% were male and median age was 67. The median ejection fraction was 26%. 70% were NYHA class III and 29% class IV. The etiology of heart failure was ischemic in 55%, and non-ischemic in 45%. There was a history of myocardial infarction in 28%, of hypertension in 24%, and of diabetes in 22%. The median baseline serum creatinine was 1.2 mg/dL and the median baseline creatinine clearance was 57 mL/min.

At baseline 100% of patients were taking loop diuretic and 95% were taking an ACE inhibitor. Other medications used at any time during the study included digoxin (78%), anticoagulants (58%), aspirin (43%), and beta-blockers (15%).

The primary endpoint for RALES was time to all-cause mortality. RALES was terminated early because of significant mortality benefit demonstrated during a planned interim analysis. Compared to placebo, spironolactone reduced the risk of death by 30% (p<0.001; 95% confidence interval 18% to 40%). Spironolactone also reduced the risk of hospitalization for cardiac causes (defined as worsening heart failure, angina, ventricular arrhythmias, or myocardial infarction) by 30% (p <0.001; 95% confidence interval 18% to 41%).

The survival curves by treatment group are shown in Figure 1.

Figure 1. Survival by Treatment Group in RALES

Figure 1
(click image for full-size original)

Mortality hazard ratios for some subgroups are shown in Figure 2. The favorable effect of spironolactone on mortality appeared similar for both genders and all age groups except patients younger than 55. There were too few non-whites in RALES to evaluate if the effects differ by race. Spironolactone’s benefit appeared greater in patients with low baseline serum potassium levels and less in patients with ejection fractions <0.2. These subgroup analyses must be interpreted cautiously.

Figure 2. Hazard Ratios of All-Cause Mortality by Subgroup in RALES

Figure 2
(click image for full-size original)

Figure 2: The size of each box is proportional to the sample size as well as the event rate. LVEF denotes left ventricular ejection fraction, Ser Creatinine denotes serum creatinine, Cr Clearance denotes creatinine clearance, and ACEI denotes angiotensin-converting enzyme inhibitor.

14.2 Hypertension

The dose response of spironolactone for hypertension has not been well characterized. In patients with hypertension, decreases in systolic blood pressure have been observed at doses ranging from 25 to 100 mg/day. Doses greater than 100 mg/day generally do not provide additional reductions in blood pressure [see Dosage and Administration (2.3)].

16 HOW SUPPLIED/STORAGE AND HANDLING

ALDACTONE 25 mg tablets are round, light yellow, film-coated, with SEARLE and 1001 debossed on one side and ALDACTONE and 25 on the other side, supplied as:

NDC Number Size
0025-1001-31 bottle of 100

ALDACTONE 50 mg tablets are oval, light orange, scored, film-coated, with SEARLE and 1041 debossed on the scored side and ALDACTONE and 50 on the other side, supplied as:

NDC Number Size
0025-1041-31 bottle of 100

ALDACTONE 100 mg tablets are round, peach-colored, scored, film-coated, with SEARLE and 1031 debossed on the scored side and ALDACTONE and 100 on the other side, supplied as:

NDC Number Size
0025-1031-31 bottle of 100

Store below 77°F (25°C).

17 PATIENT COUNSELING INFORMATION

Patients who receive ALDACTONE should be advised to avoid potassium supplements and foods containing high levels of potassium, including salt substitutes.

This product’s label may have been updated. For current full prescribing information, please visit www.pfizer.com.

Logo
(click image for full-size original)

LAB-0231-15.0

PRINCIPAL DISPLAY PANEL — 25 mg Tablet Bottle Label

Pfizer

NDC 0025-1001-31

Aldactone®
spironolactone
tablets, USP

25 mg

100 Tablets
Rx only

PRINCIPAL DISPLAY PANEL -- 25 mg Tablet Bottle Label
(click image for full-size original)

PRINCIPAL DISPLAY PANEL — 50 mg Tablet Bottle Label

Pfizer

NDC 0025-1041-31

Aldactone®
spironolactone
tablets, USP

50 mg

100 Tablets
Rx only

PRINCIPAL DISPLAY PANEL -- 50 mg Tablet Bottle Label
(click image for full-size original)

PRINCIPAL DISPLAY PANEL — 100 mg Tablet Bottle Label

Pfizer

NDC 0025-1031-31

Aldactone®
spironolactone
tablets, USP

100 mg

100 Tablets
Rx only

PRINCIPAL DISPLAY PANEL -- 100 mg Tablet Bottle Label
(click image for full-size original)
ALDACTONE
spironolactone tablet, film coated
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:0025-1001
Route of Administration ORAL DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
SPIRONOLACTONE (SPIRONOLACTONE) SPIRONOLACTONE 25 mg
Inactive Ingredients
Ingredient Name Strength
STARCH, CORN
FERRIC OXIDE RED
MAGNESIUM STEARATE
POVIDONE, UNSPECIFIED
TITANIUM DIOXIDE
HYPROMELLOSE 2910 (15000 MPA.S)
CALCIUM SULFATE DIHYDRATE
PEPPERMINT
POLYETHYLENE GLYCOL 400
CARNAUBA WAX
STEARIC ACID
Product Characteristics
Color YELLOW (light yellow) Score no score
Shape ROUND Size 9mm
Flavor Imprint Code SEARLE;1001;ALDACTONE;25
Contains
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:0025-1001-31 100 TABLET, FILM COATED in 1 BOTTLE None
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NDA NDA012151 01/21/1960
ALDACTONE
spironolactone tablet, film coated
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:0025-1041
Route of Administration ORAL DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
SPIRONOLACTONE (SPIRONOLACTONE) SPIRONOLACTONE 50 mg
Inactive Ingredients
Ingredient Name Strength
STARCH, CORN
FERRIC OXIDE RED
MAGNESIUM STEARATE
POVIDONE, UNSPECIFIED
TITANIUM DIOXIDE
HYPROMELLOSE 2910 (15000 MPA.S)
CALCIUM SULFATE DIHYDRATE
PEPPERMINT
POLYETHYLENE GLYCOL 400
CARNAUBA WAX
STEARIC ACID
Product Characteristics
Color ORANGE (light orange) Score 2 pieces
Shape OVAL Size 14mm
Flavor Imprint Code SEARLE;1041;ALDACTONE;50
Contains
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:0025-1041-31 100 TABLET, FILM COATED in 1 BOTTLE None
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NDA NDA012151 01/21/1960
ALDACTONE
spironolactone tablet, film coated
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:0025-1031
Route of Administration ORAL DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
SPIRONOLACTONE (SPIRONOLACTONE) SPIRONOLACTONE 100 mg
Inactive Ingredients
Ingredient Name Strength
STARCH, CORN
FERRIC OXIDE RED
MAGNESIUM STEARATE
POVIDONE, UNSPECIFIED
TITANIUM DIOXIDE
HYPROMELLOSE 2910 (15000 MPA.S)
CALCIUM SULFATE DIHYDRATE
PEPPERMINT
POLYETHYLENE GLYCOL 400
CARNAUBA WAX
STEARIC ACID
Product Characteristics
Color ORANGE (peach) Score 2 pieces
Shape ROUND Size 11mm
Flavor Imprint Code SEARLE;1031;ALDACTONE;100
Contains
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:0025-1031-31 100 TABLET, FILM COATED in 1 BOTTLE None
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NDA NDA012151 01/21/1960
Labeler — Pfizer Laboratories Div Pfizer Inc (134489525)
Registrant — Pfizer Inc (113480771)
Establishment
Name Address ID/FEI Operations
Packaging Coordinators, LLC 078525133 PACK (0025-1001), PACK (0025-1031), PACK (0025-1041), LABEL (0025-1001), LABEL (0025-1031), LABEL (0025-1041)
Establishment
Name Address ID/FEI Operations
Pfizer Inc 943955690 ANALYSIS (0025-1001), ANALYSIS (0025-1031), ANALYSIS (0025-1041)

Revised: 02/2021 Pfizer Laboratories Div Pfizer Inc

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