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Hyperkalemia: The most serious adverse effect of spironolactone therapy is hyperkalemia, which occurs most frequently in patients receiving potassium supplements concomitantly and in patients with renal insufficiency. Hyperkalemia can cause cardiac irregularities which may be fatal. Potassium supplementation, either in the form of medication or as a diet rich in potassium, should not ordinary be given in associated with spironolactone therapy. Excessive potassium intake may cause hyperkalemia in patients receiving spironolactone. If hyperkalemia is present, discontinue spironolactone immediately.
Fluid and Electrolyte Imbalance: 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 GI 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 fetal. Consequently, no potassium supplement should ordinarily be given with spironolactone.
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 in the presence of normal renal function.
Hyponatremia: 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 spironolactone 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.
Gynecomastia: Gynecomastia may develop in association with the use of spironolactone. The development of gynecomastia appears to be related to both dosage level and duration of therapy and is normally reversible when spironolactone is discontinued. In rare instances, some breast enlargement may persist when spironolactone is discontinued.
Renal Effects: Spironolactone therapy may cause a transient elevation of serum urea nitrogen (BUN), especially in patients with preexisting renal impairment. Spironolactone may cause mild acidosis.
Hepatic function impairment: Spironolactone should be used with caution in patients with impaired hepatic function because minor alterations of fluid and electrolyte balance may precipitate hepatic coma.
GI Effects: Anorexia, nausea, vomiting, diarrhea, abdominal cramping, gastritis, gastric bleeding, and ulceration have occurred during spironolactone therapy.
Nervous System Effects: Headache, drowsiness, lethargy, ataxia, mental confusion, and fever have occurred during spironolactone therapy. In addition, severe fatigue and lassitude have been associated with the rapid and profound weight loss that occurs at the start of high-dose spironolactone therapy in patients with primary aldosteronism.
Dermatologic and Sensitivity Reactions: Maculopapular and erythematous rashes (sometimes accompanied by eosinophilia), anaphylactic reaction, vasculitis, and urticarial have been reported rarely in patients receiving spironolactone.
Mutagenicity and Carcinogenicity: Canrenone, a major metabolite of spironolactone, and canrenoic acid are the major metabolites of potassium canrenoate. In tests using bacteria or yeast and in an in vivo mammalian system, potassium canrenoate was not mutagenic; however, it did produce a mutagenic effect in several in vitro tests in mammalian cells following metabolic activation.
Spironolactone has been shown to be tumorigenic in chronic toxicity studies in rats. Studies in rats using spironolactone dosage 25-250 times the usual human dosage resulted in a dose-related increase in benign adenomas of the thyroid and testes, a dose-related increase in proliferative changes in the livers of male rats, and an increase in malignant mammary tumors in female rats. At dosages 250 times the usual human dosage, hepatocellular carcinoma, hepatocytomegaly, and hyperplastic nodules were reported in rats. At dosages greater than 20 mg/kg daily, a dose-related incidence of myelocytic leukemia was observed in rats receiving potassium canrenoate in their diet for one year. In rats receiving potassium canrenoate for 2 years, myelocytic leukemia and hepatic, thyroid, testicular, and mammary tumors were observed. In chronic toxicity studies in rats using spironolactone dosages up to 250 times the usual human dosage, an increased incidence of leukemia was not observed.
