Aldactone

Aldactone

Tablets: 25, 50, and 100 mg

Aldactone should be stored at room temperature, below 25 C (77 F).

Pregnancy

Limited available data did not demonstrate an association of major malformations or other adverse pregnancy outcomes with spironolactone; risks may occur to the mother and fetus associated with heart failure, cirrhosis, and poorly controlled hypertension during pregnancy

Potential risk to the male fetus due to antiandrogenic properties of spironolactone; avoid spironolactone in pregnant women or advise a pregnant woman of the potential risk to a male fetus

Disease-associated maternal and embryo/fetal risks

• Pregnant women with CHF are at increased risk for preterm birth; stroke volume and heart rate increase during pregnancy, increasing cardiac output, especially during the first trimester; closely monitor pregnant patients with CHF
• Pregnant women with symptomatic cirrhosis generally have poor outcomes (eg, hepatic failure, variceal hemorrhage, preterm delivery, fetal growth restriction, and maternal death); pregnant women with cirrhosis of the liver should be monitored and managed accordingly
• Hypertension in pregnancy increases the maternal risk for preeclampsia, gestational diabetes, premature delivery, and delivery complications (eg, need for cesarean delivery, postpartum hemorrhage); hypertension increases the fetal risk for intrauterine growth restriction and death

Lactation

Unknown if distributed in human breast milk

Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.

ALDACTONE oral tablets contain 25 mg, 50 mg, or 100 mg of the aldosterone antagonist spironolactone, 17-hydroxy-7α-mercapto-3-oxo-17α-pregn-4-ene-21-carboxylic acid γ-lactone acetate, which has the following structural formula:

Spironolactone is practically insoluble in water, soluble in alcohol, and freely soluble in benzene and in chloroform.

Inactive ingredients include calcium sulfate, corn starch, flavor, hypromellose, iron oxide, magnesium stearate, polyethylene glycol, povidone, and titanium dioxide.

The following adverse reactions have been reported and, within each category (body system), are listed in order of decreasing severity.

Digestive: Gastric bleeding, ulceration, gastritis, diarrhea and cramping, nausea, vomiting.

Reproductive: Gynecomastia (see PRECAUTIONS), inability to achieve or maintain erection, irregular menses or amenorrhea, postmenopausal bleeding, breast pain. Carcinoma of the breast has been reported in patients taking ALDACTONE but a cause and effect relationship has not been established.

Hematologic: Leukopenia (including agranulocytosis), thrombocytopenia.

Hypersensitivity: Fever, urticaria, maculopapular or erythematous cutaneous eruptions, anaphylactic reactions, vasculitis.

Metabolism: Hyperkalemia, electrolyte disturbances (see WARNINGS and PRECAUTIONS).

Musculoskeletal: Leg cramps.

Nervous system /psychiatric: Lethargy, mental confusion, ataxia, dizziness, headache, drowsiness.

Liver / biliary: A very few cases of mixed cholestatic/hepatocellular toxicity, with one reported fatality, have been reported with ALDACTONE administration.

Renal: Renal dysfunction (including renal failure).

Skin: Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), drug rash with eosinophilia and systemic symptoms (DRESS), alopecia, pruritis.

Aldactone is part of the drug class:

• Aldosterone antagonists

Before taking Aldactone, tell your doctor about all of your medical conditions. Especially tell your doctor if you:

• have liver disease
• have kidney disease
• have electrolyte imbalances
• are allergic to any medications
• are pregnant or breastfeeding

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements.

WARNING

Aldactone has been shown to be a tumorigen in chronic toxicity studies in rats. Unnecessary use of this drug should be avoided.

Follow all directions on your prescription label. Do not take this medicine in larger or smaller amounts or for longer than recommended.

While using spironolactone, you may need frequent blood tests.

This medication can cause unusual results with certain medical tests. Tell any doctor who treats you that you are using spironolactone.

If you need surgery, tell the surgeon ahead of time that you are using spironolactone. You may need to stop using the medicine for a short time.

If you are being treated for high blood pressure, keep using this medication even if you feel well. High blood pressure often has no symptoms. You may need to use blood pressure medication for the rest of your life.

Store at room temperature away from heat, light, and moisture.

Get emergency medical help if you have signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Stop using spironolactone and call your doctor at once if you have:

• signs of stomach bleeding--bloody or tarry stools, coughing up blood or vomit that looks like coffee grounds;

• high potassium--slow heart rate, weak pulse, muscle weakness or limp feeling, tingly feeling;

• low sodium--confusion, slurred speech, hallucinations, severe weakness, loss of coordination, feeling unsteady, seizure (convulsions), fainting, shallow breathing (breathing may stop); or

• symptoms of any electrolyte imbalance--dry mouth, increased thirst, drowsiness, lack of energy, restless feeling, confusion, nausea, vomiting, increased urination, muscle cramps or weakness, fast heart rate, little or no urinating, or feeling like you might pass out.

Common side effects may include:

• mild nausea or vomiting, diarrhea;

• breast swelling or tenderness;

• dizziness, headache, mild drowsiness;

• leg cramps; or

• impotence, difficulty having an erection.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Aldactone is contraindicated for patients with anuria, acute renal insufficiency, significant impairment of renal excretory function, hyperkalemia, Addison's disease, and with concomitant use of eplerenone.

General

All patients receiving diuretic therapy should be observed for evidence of fluid or electrolyte imbalance, e.g., hypomagnesemia, hyponatremia, hypochloremic alkalosis, and hyperkalemia.

Serum and urine electrolyte determinations are particularly important when the patient is vomiting excessively or receiving parenteral fluids. Warning signs or symptoms of fluid and electrolyte imbalance, irrespective of cause, include dryness of the mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pains or cramps, muscular fatigue, hypotension, oliguria, tachycardia, and gastrointestinal disturbances such as nausea and vomiting. Hyperkalemia may occur in patients with impaired renal function or excessive potassium intake and can cause cardiac irregularities, which may be fatal. Consequently, no potassium supplement should ordinarily be given with Aldactone.

If hyperkalemia is suspected (warning signs include paresthesia, muscle weakness, fatigue, flaccid paralysis of the extremities, bradycardia, and shock), an electrocardiogram (ECG) should be obtained. However, it is important to monitor serum potassium levels because mild hyperkalemia may not be associated with ECG changes.

If hyperkalemia is present, Aldactone should be discontinued immediately. With severe hyperkalemia, the clinical situation dictates the procedures to be employed. These may include the intravenous administration of calcium chloride solution, sodium bicarbonate solution and/or the oral or parenteral administration of glucose with a rapid-acting insulin preparation. These are temporary measures to be repeated as required. Cationic exchange resins such as sodium polystyrene sulfonate may be orally or rectally administered. Persistent hyperkalemia may require dialysis.

Reversible hyperchloremic metabolic acidosis, usually in association with hyperkalemia, has been reported to occur in some patients with decompensated hepatic cirrhosis, even in the presence of normal renal function.

Dilutional hyponatremia, manifested by dryness of the mouth, thirst, lethargy, and drowsiness, and confirmed by a low serum sodium level, may be caused or aggravated, especially when Aldactone is administered in combination with other diuretics, and dilutional hyponatremia may occur in edematous patients in hot weather; appropriate therapy is water restriction rather than administration of sodium, except in rare instances when the hyponatremia is life-threatening.

Aldactone therapy may cause a transient elevation of BUN, especially in patients with pre-existing renal impairment. Aldactone may cause mild acidosis.

Gynecomastia may develop in association with the use of Aldactone; physicians should be alert to its possible onset. The development of gynecomastia appears to be related to both dosage level and duration of therapy and is normally reversible when Aldactone is discontinued. In rare instances, some breast enlargement may persist when Aldactone is discontinued.

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.

Information for patients

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

Laboratory tests

Periodic determination of serum electrolytes to detect possible electrolyte imbalance should be done at appropriate intervals, particularly in the elderly and those with significant renal or hepatic impairments.

Drug interactions

Concomitant administration of ACE inhibitors with potassium-sparing diuretics has been associated with severe hyperkalemia.

Concomitant administration may lead to severe hyperkalemia.

Potentiation of orthostatic hypotension may occur.

Intensified electrolyte depletion, particularly hypokalemia, may occur.

Aldactone reduces the vascular responsiveness to norepinephrine. Therefore, caution should be exercised in the management of patients subjected to regional or general anesthesia while they are being treated with Aldactone.

Possible increased responsiveness to the muscle relaxant may result.

Lithium generally should not be given with diuretics. Diuretic agents reduce the renal clearance of lithium and add a high risk of lithium toxicity.

In some patients, the administration of an NSAID can reduce the diuretic, natriuretic, and antihypertensive effect of loop, potassium-sparing, and thiazide diuretics. Combination of NSAIDs, e.g., indomethacin, with potassium-sparing diuretics has been associated with severe hyperkalemia. Therefore, when Aldactone and NSAIDs are used concomitantly, the patient should be observed closely to determine if the desired effect of the diuretic is obtained.

Aldactone has been shown to increase the half-life of digoxin. This may result in increased serum digoxin levels and subsequent digitalis toxicity. It may be necessary to reduce the maintenance and digitalization doses when Aldactone is administered, and the patient should be carefully monitored to avoid over- or under-digitalization.

Hyperkalemic metabolic acidosis has been reported in patients given Aldactone concurrently with cholestyramine.

Drug/Laboratory test interactions

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

Carcinogenesis, mutagenesis, impairment of fertility

Orally administered Aldactone has been shown to be a tumorigen in dietary administration studies performed in rats, with its proliferative effects manifested on endocrine organs and the liver. In an 18-month study using doses of about 50, 150, and 500 mg/kg/day, there were statistically significant increases in benign adenomas of the thyroid and testes and, in male rats, a dose-related increase in proliferative changes in the liver (including hepatocytomegaly and hyperplastic nodules). In a 24-month study in which the same strain of rat was administered doses of about 10, 30, 100, and 150 mg Aldactone/kg/day, the range of proliferative effects included significant increases in hepatocellular adenomas and testicular interstitial cell tumors in males, and significant increases in thyroid follicular cell adenomas and carcinomas in both sexes. There was also a statistically significant, but not dose-related, increase in benign uterine endometrial stromal polyps in females.

A dose-related (above 20 mg/kg/day) incidence of myelocytic leukemia was observed in rats fed daily doses of potassium canrenoate (a compound chemically similar to Aldactone and whose primary metabolite, canrenone, is also a major product of Aldactone in man) for a period of one year. In two-year studies in the rat, oral administration of potassium canrenoate was associated with myelocytic leukemia and hepatic, thyroid, testicular, and mammary tumors.

Neither Aldactone nor potassium canrenoate produced mutagenic effects in tests using bacteria or yeast. In the absence of metabolic activation, neither Aldactone nor potassium canrenoate has been shown to be mutagenic in mammalian tests in vitro. In the presence of metabolic activation, Aldactone has been reported to be negative in some mammalian mutagenicity tests in vitro and inconclusive (but slightly positive) for mutagenicity in other mammalian tests in vitro. In the presence of metabolic activation, potassium canrenoate has been reported to test positive for mutagenicity in some mammalian tests in vitro, inconclusive in others, and negative in still others.

In a three-litter reproduction study in which female rats received dietary doses of 15 and 50 mg Aldactone/kg/day, there were no effects on mating and fertility, but there was a small increase in incidence of stillborn pups at 50 mg/kg/day. When injected into female rats (100 mg/kg/day for 7 days, i.p.), Aldactone 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. Aldactone (100 mg/kg/day), administered i.p. to female mice during a two-week cohabitation period with untreated males, decreased the number of mated mice that conceived (effect shown to be caused by an inhibition of ovulation) and decreased the number of implanted embryos in those that became pregnant (effect shown to be caused by an inhibition of implantation), and at 200 mg/kg, also increased the latency period to mating.

Pregnancy

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. There are no adequate and well-controlled studies with Aldactone in pregnant women. Aldactone has known endocrine effects in animals including progestational and antiandrogenic effects. The antiandrogenic effects can result in apparent estrogenic side effects in humans, such as gynecomastia. Therefore, the use of Aldactone in pregnant women requires that the anticipated benefit be weighed against the possible hazards to the fetus.

Nursing mothers

Canrenone, a major (and active) metabolite of Aldactone, appears in human breast milk. Because Aldactone has been found to be tumorigenic in rats, a decision should be made whether to discontinue the drug, taking into account the importance of the drug to the mother. If use of the drug is deemed essential, an alternative method of infant feeding should be instituted.

Pediatric use

Safety and effectiveness in pediatric patients have not been established.

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:

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:

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:

Store below 77°F (25°C).

LAB-0231-11.0
October 2016

Spironolactone is a potassium-sparing diuretic (water pill) that prevents your body from absorbing too much salt and keeps your potassium levels from getting too low.

Spironolactone is used to diagnose or treat a condition in which you have too much aldosterone in your body. Aldosterone is a hormone produced by your adrenal glands to help regulate the salt and water balance in your body.

Spironolactone also treats fluid retention (edema) in people with congestive heart failure, cirrhosis of the liver, or a kidney disorder called nephrotic syndrome. This medication is also used to treat or prevent hypokalemia (low potassium levels in the blood).

Spironolactone may also be used for purposes not listed in this medication guide.

Your pharmacist can provide more information about spironolactone.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

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You should not use Aldactone if you have kidney disease, high levels of potassium in your blood, Addison's disease (an adrenal gland disorder), if you are unable to urinate, or if you are also taking eplerenone.

In animal studies, Aldactone caused certain types of cancers or tumors. It is not known whether these effects would occur in people using this medicine. Ask your doctor about your risk.

You should not use Aldactone if you are allergic to spironolactone, or if you have:

• kidney disease, or if you are unable to urinate;

• Addison's disease (an adrenal gland disorder);

• high levels of potassium in your blood (hyperkalemia); or

• if you are also taking eplerenone.

To make sure Aldactone is safe for you, tell your doctor if you have:

• liver disease;

• heart disease;

• an electrolyte imbalance (such as low levels of magnesium in your blood); or

• if you take an NSAID (nonsteroidal anti-inflammatory drug), cholestyramine, heparin, lithium, heart or blood pressure medication, potassium supplements, steroid medicine, or another diuretic.

In animal studies, Aldactone caused certain types of tumors, some of which were cancerous. However, very high doses are used in animal studies. It is not known whether these effects would occur in people using regular doses. Ask your doctor about your risk.

It is not known whether Aldactone will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medication.

Spironolactone can pass into breast milk and may harm a nursing baby. You should not breast-feed while using this medicine.

Take Aldactone exactly as prescribed by your doctor. Follow all directions on your prescription label. Do not take this medicine in larger or smaller amounts or for longer than recommended.

While using Aldactone, you may need frequent blood tests.

Aldactone cause unusual results with certain medical tests. Tell any doctor who treats you that you are using this medicine.

If you need surgery, tell the surgeon ahead of time that you are using Aldactone. You may need to stop using the medicine for a short time.

If you are being treated for high blood pressure, keep using this medication even if you feel well. High blood pressure often has no symptoms. You may need to use blood pressure medication for the rest of your life.

Store at room temperature away from heat, light, and moisture.

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Get emergency medical help if you have any signs of an allergic reaction to Aldactone: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Stop using Aldactone and call your doctor at once if you have:

• signs of stomach bleeding - bloody or tarry stools, coughing up blood or vomit that looks like coffee grounds;

• high potassium - slow heart rate, weak pulse, muscle weakness or limp feeling, tingly feeling;

• low sodium - confusion, slurred speech, hallucinations, severe weakness, loss of coordination, feeling unsteady, seizure (convulsions), fainting, shallow breathing (breathing may stop); or

• symptoms of any electrolyte imbalance - dry mouth, increased thirst, drowsiness, lack of energy, restless feeling, confusion, nausea, vomiting, increased urination, muscle cramps or weakness, fast heart rate, little or no urinating, or feeling like you might pass out.

Common Aldactone side effects may include:

• mild nausea or vomiting, diarrhea;

• breast swelling or tenderness;

• dizziness, headache, mild drowsiness;

• leg cramps; or

• impotence, difficulty having an erection.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Storage

Tablet: Store below 77°F (25°C)

PO suspension: Store at 68-77°F (20-25°C); excursions permitted to 59-86°F (15-30°C); shake well before use, dispense in a tight container as defined in the USP