ALDACTONE- spironolactone tablet, film coated

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

SPIRONOLACTONE (UNII: 27O7W4T232) (SPIRONOLACTONE - UNII:27O7W4T232)

Available from:

Pfizer Laboratories Div Pfizer Inc

INN (International Name):

SPIRONOLACTONE

Composition:

SPIRONOLACTONE 25 mg

Administration route:

ORAL

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

ALDACTONE is indicated for treatment of NYHA Class III–IV heart failure and reduced ejection fraction to increase survival, manage edema, and reduce the need for hospitalization for heart failure. ALDACTONE is usually administered in conjunction with other heart failure therapies. ALDACTONE is indicated as add-on therapy for the treatment of hypertension, to lower blood pressure in patients who are not adequately controlled on other agents. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes. Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. Many patients will require more than one drug to achieve blood pressure goals. For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education Program's Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC). Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. The largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly. Elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmHg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. Relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal. Some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). These considerations may guide selection of therapy. ALDACTONE is indicated for the management of edema in the following settings: Because it increases serum potassium, ALDACTONE may be useful for treating edema when administration of other diuretics has caused hypokalemia. ALDACTONE is indicated in the following settings: ALDACTONE is contraindicated in the patients with: Risk Summary Based on mechanism of action and findings in animal studies, spironolactone may affect sex differentiation of the male during embryogenesis (see Data) . Rat embryofetal studies report feminization of male fetuses and endocrine dysfunction in females exposed to spironolactone in utero. Limited available data from published case reports and case series did not demonstrate an association of major malformations or other adverse pregnancy outcomes with spironolactone. There are risks to the mother and fetus associated with heart failure, cirrhosis and poorly controlled hypertension during pregnancy (see Error! Hyperlink reference not valid. ) . Because of the potential risk to the male fetus due to anti-androgenic properties of spironolactone and animal data, avoid spironolactone in pregnant women or advise a pregnant woman of the potential risk to a male fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2%–4% and 15%–20%, respectively. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk Pregnant women with congestive heart failure are at increased risk for preterm birth. Stroke volume and heart rate increase during pregnancy, increasing cardiac output, especially during the first trimester. Clinical classification of heart disease may worsen with pregnancy and lead to maternal death. Closely monitor pregnant patients for destabilization of their heart failure. Pregnant women with symptomatic cirrhosis generally have poor outcomes including hepatic failure, variceal hemorrhage, preterm delivery, fetal growth restriction and maternal death. Outcomes are worse with coexisting esophageal varices. Pregnant women with cirrhosis of the liver should be carefully monitored and managed accordingly. Hypertension in pregnancy increases the maternal risk for pre-eclampsia, gestational diabetes, premature delivery, and delivery complications (e.g., need for cesarean section, and post-partum hemorrhage). Hypertension increases the fetal risk for intrauterine growth restriction and intrauterine death. Data Animal Data Teratology studies with ALDACTONE have been carried out in mice and rabbits at doses of up to 20 mg/kg/day. On a body surface area basis, this dose in the mouse is substantially below the maximum recommended human dose and, in the rabbit, approximates the maximum recommended human dose. No teratogenic or other embryotoxic effects were observed in mice, but the 20 mg/kg dose caused an increased rate of resorption and a lower number of live fetuses in rabbits. Because of its antiandrogenic activity and the requirement of testosterone for male morphogenesis, ALDACTONE may have the potential for adversely affecting sex differentiation of the male during embryogenesis. When administered to rats at 200 mg/kg/day between gestation days 13 and 21 (late embryogenesis and fetal development), feminization of male fetuses was observed. Offspring exposed during late pregnancy to 50 and 100 mg/kg/day doses of ALDACTONE exhibited changes in the reproductive tract including dose-dependent decreases in weights of the ventral prostate and seminal vesicle in males, ovaries and uteri that were enlarged in females, and other indications of endocrine dysfunction, that persisted into adulthood. ALDACTONE has known endocrine effects in animals including progestational and antiandrogenic effects. Risk Summary Spironolactone is not present in breastmilk; however, limited data from a lactating woman at 17 days postpartum reports the presence of the active metabolite, canrenone, in human breast milk in low amounts that are expected to be clinically inconsequential. In this case, there were no adverse effects reported for the breastfed infant after short term exposure to spironolactone; however, long term effects on a breastfed infant are unknown. There are no data on spironolactone effects on milk production. Consider the developmental and health benefits of breastfeeding along with the mother's clinical need for spironolactone and any potential adverse effects on the breastfed child from spironolactone or from the underlying maternal condition. Safety and effectiveness in pediatric patients have not been established. ALDACTONE is substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, monitor renal function. ALDACTONE is substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Patients with renal impairment are at increased risk of hyperkalemia. Monitor potassium closely. ALDACTONE can cause sudden alterations of fluid and electrolyte balance which may precipitate impaired neurological function, worsening hepatic encephalopathy and coma in patients with hepatic disease with cirrhosis and ascites. In these patients, initiate ALDACTONE in the hospital [see Dosage and Administration (2.4) and Clinical Pharmacology (12.3)] . Clearance of spironolactone and its metabolites is reduced in patients with cirrhosis. In patients with cirrhosis, start with lowest initial dose and titrate slowly [see Dosage and Administration (2.4) and Clinical Pharmacology (12.3)] .

Product summary:

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).

Authorization status:

New Drug Application

Summary of Product characteristics

ALDACTONE- SPIRONOLACTONE TABLET, FILM COATED
PFIZER LABORATORIES DIV PFIZER INC
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
ALDACTONE SAFELY AND
EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR ALDACTONE.
ALDACTONE (SPIRONOLACTONE) TABLETS FOR ORAL USE
INITIAL U.S. APPROVAL: 1960
INDICATIONS AND USAGE
ALDACTONE is an aldosterone antagonist indicated for:
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DOSAGE AND ADMINISTRATION
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DOSAGE FORMS AND STRENGTHS
Tablets: 25 mg, 50 mg, and 100 mg (3)
CONTRAINDICATIONS
ALDACTONE is contraindicated in patients with (4):
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WARNINGS AND PRECAUTIONS
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ADVERSE REACTIONS
The most common adverse reaction with ALDACTONE treatment is
gynecomastia (5.4, 6).
TO REPORT SUSPECTED ADVERSE REACTIONS, CONTACT PFIZER, INC. AT
1-800-438-1985 OR FDA AT
1-800-FDA-1088 OR _WWW.FDA.GOV/SAFETY/MEDWATCH_.
®
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 (1.1).
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 (1.2).
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 (1.3).
Treatment of primary hyperaldosternism for: (1.4)
o
o
Short-term preoperative treatment
Long-term maintenance for patients with discrete aldosterone-producing
adrenal adenomas who
are not candidates for surgery and patients with bilateral micro or
macronodular adrenal
hyperplasia
Heart Failure: Initiate treatment at 25 mg once daily (2.2).
Hypertension: Initiate treatment at 25 to 100 mg daily in either
si