Yes

Diuretic, Potassium Sparing

Management of edema associated with excessive aldosterone excretion; hypertension; primary hyperaldosteronism; hypokalemia; treatment of hirsutism; cirrhosis of liver accompanied by edema or ascites

D

Clinical effects on the fetus: No data available on crossing the placenta. 1 report of oral cleft. Generally, use of diuretics during pregnancy is avoided due to risk of decreased placental perfusion.

Breast-feeding/lactation: Crosses into breast milk. American Academy of Pediatrics considers compatible with breast-feeding.

Hypersensitivity to spironolactone or any component; anuria; acute renal insufficiency; significant impairment of renal excretory function; hyperkalemia; pregnancy

Avoid potassium supplements, potassium-containing salt substitutes, a diet rich in potassium, or other drugs that can cause hyperkalemia. Monitor for fluid and electrolyte imbalances. Gynecomastia is related to dose and duration of therapy. Diuretic therapy should be carefully used in severe hepatic dysfunction; electrolyte and fluid shifts can cause or exacerbate encephalopathy.

• Incidence of adverse events is not always reported. (Mean daily dose 26 mg)

Central nervous system: Disorders (23%, placebo 21%) which may include drowsiness, lethargy, headache, mental confusion, drug fever, ataxia, fatigue

Dermatologic: Maculopapular, erythematous cutaneous eruptions, urticaria, hirsutism, eosinophilia

Endocrine & metabolic: Gynecomastia (men 9%; placebo 1%), breast pain (men 2%; placebo 0.1%), serious hyperkalemia (2%, placebo 1%), hyponatremia, dehydration, hyperchloremic metabolic acidosis in decompensated hepatic cirrhosis, inability to achieve or maintain an erection, irregular menses, amenorrhea, postmenopausal bleeding

Gastrointestinal: Disorders (29%, placebo 29%) which may include anorexia, nausea, cramping, diarrhea, gastric bleeding, ulceration, gastritis, vomiting

Genitourinary: Disorders (12%, placebo 11%)

Hematologic: Agranulocytosis

Hepatic: Cholestatic/hepatocellular toxicity

Renal: Increased BUN concentration

Respiratory: Disorders (32%, placebo 34%)

Miscellaneous: Deepening of the voice, anaphylactic reaction, breast cancer

Symptoms of overdose include drowsiness, confusion, clinical signs of dehydration and electrolyte imbalance, hyperkalemia; ingestion of large amounts of potassium-sparing diuretics, may result in life-threatening hyperkalemia.

This can be treated with I.V. glucose, with concurrent regular insulin; sodium bicarbonate may also be used as a temporary measure. If needed, Kayexalate® oral or rectal solutions in sorbitol may also be used.

Angiotensin-converting enzyme inhibitors can cause hyperkalemia, especially in patients with renal impairment, potassium-rich diets, or on other drugs causing hyperkalemia; avoid concurrent use or monitor closely.

Cholestyramine can cause hyperchloremic acidosis in cirrhotic patients; avoid concurrent use.

Digoxin's positive inotropic effect may be reduced; serum levels of digoxin may increase.

Mitotane loses its effect; avoid concurrent use.

Potassium supplements may increase potassium retention and cause hyperkalemia; avoid concurrent use.

Salicylates may interfere with the natriuretic action of spironolactone.

Protect from light

Competes with aldosterone for receptor sites in the distal renal tubules, increasing sodium chloride and water excretion while conserving potassium and hydrogen ions; may block the effect of aldosterone on arteriolar smooth muscle as well

Protein binding: 91% to 98%

Metabolism: In the liver to multiple metabolites, including canrenone (active)

Half-life: 78-84 minutes

Time to peak serum concentration: Within 1-3 hours (primarily as the active metabolite)

Elimination: Urinary and biliary excretion

Administration with food increases absorption. To reduce delay in onset of effect, a loading dose of 2 or 3 times the daily dose may be administered on the first day of therapy. Oral:

Children:

Diuretic, hypertension: 1.5-3.5 mg/kg/day or 60 mg/m²/day in divided doses every 6-24 hours

Diagnosis of primary aldosteronism: 125-375 mg/m²/day in divided doses

Vaso-occlusive disease: 7.5 mg/kg/day in divided doses twice daily (not FDA approved)

Adults:

Edema, hypertension, hypokalemia: 25-200 mg/day in 1-2 divided doses

Diagnosis of primary aldosteronism: 100-400 mg/day in 1-2 divided doses

Hirsutism in women: 50-200 mg/day in 1-2 divided doses

Elderly: Initial: 25-50 mg/day in 1-2 divided doses, increasing by 25-50 mg every 5 days as needed.

Dosing interval in renal impairment:

Cl_cr 10-50 mL/minute: Administer every 12-24 hours.

Cl_cr <10 mL/minute: Avoid use.

This diuretic does not cause you to lose potassium; because salt substitutes and low-salt milk may contain potassium, do not use these products without checking with your physician, too much potassium can be as harmful as too little; should be administered with food, avoid natural licorice

Blood pressure, serum electrolytes (potassium, sodium), renal function, I & O ratios and daily weight throughout therapy

May cause false elevation in serum digoxin concentrations measured by RIA

There has been increased interest in spironolactone in heart failure and in hypertension. In severe heart failure, spironolactone (25 mg/day), when combined with maximal standard therapy, resulted in a striking improvement in cardiovascular outcome ( N Engl J Med, 1999, 341:709-17). The beneficial effect of spironolactone suggests that elevated aldosterone levels in heart failure may have considerable pathophysiologic significance. Spironolactone should be considered in patients with severe heart failure on standard therapy.

May cause drowsiness, dizziness, nervousness, or confusion

Has been used to treat lithium-related edema

No information available to require special precautions

No effects or complications reported

Take as directed, with meals or milk. This diuretic does not cause potassium loss; avoid excessive potassium intake (eg, salt substitutes, low-salt foods, bananas, nuts). Weigh yourself weekly at the same time, in the same clothes, and report weight loss more than 5 lb/week. You may experience dizziness, drowsiness, headache; use caution when driving or engaging in tasks requiring alertness until response to drug is known. Small frequent meals, frequent mouth care, sucking lozenges, or chewing gum may reduce dry mouth, nausea, or vomiting. You may experience decreased sexual ability (reversible with discontinuing of medication). Report mental confusion; clumsiness; persistent fatigue, chills, numbness, or muscle weakness in hands, feet, or face; acute persistent diarrhea; breast tenderness or increased body hair in females; breast enlargement or inability to achieve erection in males; chest pain, rapid heartbeat or palpitations; or difficulty breathing. Pregnancy precautions: Do not get pregnant while taking this medication; use appropriate barrier contraceptive measures.

Diuretic effect may be delayed 2-3 days and maximum hypertensive may be delayed 2-3 weeks; monitor I & O ratios and daily weight throughout therapy

Tablet: 25 mg, 50 mg, 100 mg

A 5 mg/mL suspension may be made by crushing tablets, levigating with a small amount of distilled water or glycerin; dilute with 1 part Cologel® and 2 parts simple syrup and/or cherry syrup to make the final concentration; spironolactone 5 mg/mL plus hydrochlorothiazide 5 mg/mL were found stable for 60 days in refrigerator in a 1:1 preparation in Ora-Sweet®/Ora-Plus®, in Ora-Sweet® SF/Ora-Plus®, and in cherry syrup

Allen LV and Erickson III MA, "Stability of Labetalol Hydrochloride, Metoprolol Tartrate, Verapamil Hydrochloride, and Spironolactone With Hydrochlorothiazide in Extemporaneously Compounded Oral Liquids," Am J Health Syst Pharm, 1996, 53:2304-9.

Handbook on Extemporaneous Formulations, Bethesda, MD: American Society of Hospital Pharmacists, 1987.

Nahata MC, Morosco RS, and Hipple TF, "Stability of Spironolactone in an Extemporaneously Prepared Suspension at Two Temperatures," Ann Pharmacother, 1993, 27:1198-9.

Foukaridis GN, "Influence of Spironolactone and Its Metabolite Canrenone on Serum Digoxin Assays," Ther Drug Monit, 1990, 12(1):82-4.

Karim A, "Spironolactone: Disposition, Metabolism, Pharmacodynamics, and Bioavailability," Drug Metab Rev, 1978, 8(1):151-88.

Renkes P, Gaucher P, and Trechot P, "Spironolactone and Hepatic Toxicity," JAMA, 1995, 273(5):376-7.

Skluth HA and Gums JG, "Spironolactone: A Re-examination," DICP, 1990, 24(1):52-9.

Tweeddale MG and Ogilvie RI, "Antagonism of Spironolactone-Induced Natriuresis by Aspirin in Man," N Engl J Med, 1973, 289(4):198-200.

Zapater P and Alba D, "Acidosis and Extreme Hypokalemia Associated With Cholestyramine and Spironolactone," Ann Pharmacother, 1995, 29(2):199-200.