ALDACTONE (Spironolactone Tablets, USP) Warnings And Precautions

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Avoid potassium supplements, salt substitutes and foods containing high levels of potassium (e.g., bananas, prunes, raisins and orange juice).

Follow your doctor's directions for a low-salt or low-sodium diet and daily exercise program.

General

Use only for "Indications": Use ALDACTONE (spironolactone) only for conditions described under "INDICATIONS".

Potassium (K+) Supplementation: The concurrent administration of potassium supplements, a diet rich in potassium, or other K+-sparing diuretics is not recommended as this may induce hyperkalemia.

Somnolence and dizziness: Somnolence and dizziness have been reported to occur in some patients. Caution is advised when driving or operating machinery until the response to initial treatment has been determined.

Carcinogenesis and Mutagenesis

Tumorigenicity: Spironolactone, in chronic toxicity studies, has been shown to be a tumorigen in rats. Breast cancer and other neoplasms (intestinal, pancreas, etc) have been reported in postmarket surveillance.

Endocrine and Metabolism

Gynecomastia: Gynecomastia may develop with the use of ALDACTONE and physicians should be advised of its possible occurrence. The development of gynecomastia appears to be related to both dosage and duration of therapy and is normally reversible when the drug is discontinued. If gynecomastia develops, discontinue the drug. In rare instances some breast enlargement may persist.

Hyperchloremic metabolic acidosis: Reversible hyperchloremic metabolic acidosis, usually in association with hyperkalemia, has been reported to occur in some patients with decompensated hepatic cirrhosis, even when renal function is normal. Caution should be used in treating patients with acute or severe liver impairments, since vigorous diuretic therapy may precipitate hepatic encephalopathy.

Acidosis and Renal Function: Rare reports of acidosis have been reported with ALDACTONE.

Hematologic

Electrolyte Balance: Because of the diuretic action of ALDACTONE patients should be carefully evaluated for possible disturbance of fluid and electrolyte balance, due to the possibility of hyperkalemia, hypochloremic alkalosis, hyponatremia and possible blood urea nitrogen (BUN)elevation, especially the elderly and/or patients with pre-existing impaired renal or hepatic function.

a) Hyperkalemia

Hyperkalemia may occur in patients treated with ALDACTONE if the potassium intake is excessive. This can cause cardiac irregularities, some of which may be fatal. Hyperkalemia may also occur even in the absence of potassium supplementation, particularly in patients with impaired renal function, elderly patients, or patients with diabetes. Consequently, no potassium supplementation should ordinarily be given with ALDACTONE. ALDACTONE should not be administered concurrently with other potassium-sparing diuretics. ALDACTONE, when used with angiotensin converting enzyme (ACE) inhibitors, nonsteroidal anti-inflammatory drugs, Angiotensin II antagonists, other aldosterone blockers, even in the presence of a diuretic, has been associated with severe hyperkalemia (See Drug Interactions section).
Concomitant use of spironolactone with heparin, low molecular weight heparin, or other drugs or conditions known to cause hyperkalemia, may lead to severe hyperkalemia (See Contraindications, Drug Interactions section).

Hyperkalemia in Patients with Moderate to Severe Heart Failure

As hyperkalemia may be fatal, it is critical to monitor and manage serum potassium in patients with heart failure receiving ALDACTONE. Avoid using other potassium-sparing diuretics. Avoid using oral potassium supplements in patients with serum potassium > 3.5 mEq/L. No information is available regarding patients with serum creatinine > 2.5 mg/dL or a recent increase in serum creatinine >25%. The recommended monitoring for potassium and creatinine is one week after initiation or increase in dose of ALDACTONE, monthly for the first 3 months, then quarterly for a year, and then every 6 months. Discontinue or interrupt treatment for serum potassium > 5 mEq/L or for serum creatinine > 4 mg/dL.

Hyperkalemia in Patients with Diabetes
Diabetic patients who are treated with ALDACTONE should also be treated with caution as they have an increased risk of hyperkalemia. The status of the patient’s renal function and serum potassium levels should be assessed prior to initiating treatment and repeated within a few days and a few weeks thereafter in the patient at risk, especially in elderly patients. The recommended monitoring for potassium and creatinine is one week after initiation or increase in dose of spironolactone, monthly for the first 3 months, then quarterly for a year, and then every 6 months.
Hyperkalemia can be treated promptly by rapid intravenous administration of glucose (20 to 50%) and regular insulin, using 0.25 to 0.5 units of insulin per gram of glucose. This is a temporary measure to be repeated if required. ALDACTONE should be discontinued and potassium intake (including dietary potassium) restricted.

b) Hyponatremia
During the administration of ALDACTONE patients suffering from sodium depletion must be attentively monitored and signs of electrolyte imbalance must be carefully checked.

ALDACTONE may, if administered concomitantly with other diuretics, cause or aggravate hyponatremia, as manifested by dryness of the mouth, thirst, lethargy, and drowsiness.

Hepatic/Biliary/Pancreatic

Impaired Hepatic Function: ALDACTONE should be used with caution in patients with impaired hepatic function because minor alterations of fluid and electrolyte balance may precipitate hepatic coma.

Management of Cirrhosis: Although high doses of ALDACTONE are required to treat edema and ascites in patients with cirrhosis, the drug dosage may be decreased before diuresis is complete to avoid the possibility of dehydration.

Neurologic: Lithium generally should not be given with diuretics (See DRUG INTERACTIONS).

Sexual Function/Reproduction

In a reproduction study in which female rats received dietary doses of 15 and 50 mg/kg/day spironolactone, there were no effects on mating or fertility, but there was a small increase in incidence of stillborn pups at the higher dose. When injected into female rats (100 mg/kg/day, 7 days i.p.) spironolactone was found to increase the length of the estrous cycle by prolonging diestrus during treatment and inducing constant diestrus during a two-week, post-treatment observation period. These effects were associated with retarded ovarian follicle development and a reduction in circulating estrogen levels, which would be expected to impair mating, fertility and fecundity. Spironolactone (100 mg/kg/day i.p.) administered to female mice decreased the number of mated mice that conceived, and decreased the number of implanted embryos in those that became pregnant; at 200 mg/kg/day it also increased the latency period to mating.

Special Populations

Pregnant Women: Spironolactone and its metabolites do cross the placental barrier. There are no studies in pregnant women. Therefore, the use of ALDACTONE requires that the potential benefits be weighed against the possible hazard to the mother and fetus.

Spironolactone was devoid of teratogenic effects in mice. Rabbits receiving spironolactone showed reduced conception rate, increased resorption rate, and lower number of live births. No embryotoxic effects were seen in rats administered high dosages, but limited, dose-related hypoprolactinemia and decreased ventral prostate and seminal vesicle weights in males, and increased leutinizing hormone secretion and ovarian and uterine weights in females were reported. Feminization of the external genitalia of male fetuses was reported in another rat study.

Nursing Women: see CONTRAINDICATIONS

Canrenone, a major (and active) metabolite of spironolactone, appears in human breast milk. Because of the unknown potential for adverse events on the breast-feeding infant, a decision should be made whether to discontinue breast-feeding or discontinue the drug, taking into account the importance of the drug to the mother.

Monitoring and Laboratory Tests

General: ALDACTONE therapy may cause transient elevation of BUN, especially in patients with pre‑existing renal impairment.

Several reports of possible interference with digoxin radioimmunoassays by spironolactone or its metabolites have appeared in the literature. Neither the extent nor the potential clinical significance of this interference (which may be assay‑specific) has been fully established.

Discontinue spironolactone for at least 4, and preferably 7, days prior to plasma cortisol determinations, if they are to be done by the method of Mattingly, that is, by fluorometric assay. No interference has been demonstrated with the competitive protein binding technique or radioimmunoassay technique.

Adrenal Vein Catheterization and Plasma Renin Activity: Discontinue spironolactone several days prior to adrenal vein catheterization for measurement of aldosterone concentrations and measurements of plasma renin activity.