Spironolactone (Aldactone)

1. Health Canada Product Monograph — Spironolactone

• Spironolactone is used to help diagnose and treat primary hyperaldosteronism, including preparation for surgery or long-term management in patients unsuitable for surgery.
• Spironolactone is used to manage fluid retention (edema) caused by congestive heart failure, when the patient responds only partially to or cannot tolerate other treatments.
• Spironolactone is used to manage fluid retention and ascites caused by cirrhosis of the liver, alongside bed rest and dietary sodium and fluid restriction.
• Spironolactone is used to help remove excess fluid in nephrotic syndrome when other diuretics and steroid treatments have not worked.
• Spironolactone is used, usually together with other medications, to treat essential hypertension when other treatments are inadequate or unsuitable.
• Spironolactone is used to treat low blood potassium (hypokalemia) when other measures are inappropriate or inadequate, including in patients on digitalis therapy.

Contraindicated in pregnancy. Confirm pregnancy status and discuss alternative therapy with the prescriber before dispensing.

• Spironolactone must not be used during pregnancy; it crosses the placenta and animal studies have shown effects on fetal development, including feminization of male fetuses' genitals in one study.

• Spironolactone must not be used while breastfeeding, since its active metabolite canrenone passes into human breast milk and its effects on a nursing infant are unknown.

• Older adults may respond differently to spironolactone in terms of safety or effectiveness, and caution is advised, particularly in those with reduced liver or kidney function.

• Health Canada has not authorized spironolactone for use in patients under 18 years of age, as its safety and effectiveness have not been established in this population.

• For diagnosing primary hyperaldosteronism, spironolactone is typically given at 400 mg per day for 3 to 4 weeks (long test) or 400 mg per day for 4 days (short test); once confirmed, doses of 75 mg to 400 mg daily may be used before surgery or for long-term management.
• For edema from heart failure, cirrhosis, or nephrotic syndrome, treatment usually starts at 100 mg per day, with a range of 25 mg to 200 mg daily, or up to 400 mg daily for cirrhosis with a low urinary sodium-to-potassium ratio, continued for at least 5 days before assessing response.
• For essential hypertension, treatment typically starts at 50 mg to 100 mg per day, with most patients responding to doses up to 200 mg per day after a stabilization period of about 2 weeks.
• For hypokalemia, the usual dose ranges from 25 mg to 100 mg per day.
• Spironolactone is contraindicated in severe kidney impairment, so kidney function should be checked before and during treatment.
• If a dose is missed, take it as soon as remembered, but skip it entirely if it is almost time for the next dose; never double up to make up for a missed dose.

If overdose is suspected, seek emergency medical attention immediately or contact your regional Poison Control Centre without delay.

• No fatal overdoses of spironolactone alone have been reported, though death could occur indirectly through severe hyperkalemia.
• Overdose symptoms include nausea and vomiting, and less commonly drowsiness, dizziness, mental confusion, diarrhea, or a skin rash.
• There is no specific antidote for spironolactone overdose; inducing vomiting or stomach lavage may be considered, and the drug should be stopped with potassium intake, including from food, restricted.
• Overdose symptoms typically resolve promptly once spironolactone is stopped, but hyperkalemia may be made worse and needs monitoring.

• Nausea may occur.
• Stomach cramping or diarrhea may occur.
• Headache may occur.
• Drowsiness or lethargy may occur.
• Dizziness may occur.
• Unsteadiness (ataxia) may occur.
• Mental confusion may occur.
• Changes in sex drive (libido) may occur.
• Leg cramps or muscle spasms may occur.

Serious side effects require immediate discussion with the prescriber or emergency care.

• Gynecomastia (breast enlargement in men) may develop, related to both dose and how long the drug is taken; it usually reverses after stopping spironolactone, though rarely some enlargement persists.
• High blood potassium (hyperkalemia) can develop and, if severe, may cause dangerous heart rhythm problems.
• Severe skin reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug rash with eosinophilia and systemic symptoms (DRESS), have been reported.
• Serious liver problems, including a mixed cholestatic/hepatocellular type of liver injury, have been reported rarely, with at least one reported death.
• Blood disorders, including low white blood cell counts (leukopenia, including agranulocytosis), low platelet counts, and anemia, have been reported.
• Rhabdomyolysis (serious muscle breakdown) has been reported.
• Kidney dysfunction, including acute kidney failure, has been reported.
• Serious allergic reactions, including anaphylaxis and vasculitis, have been reported.
• Breast cancer and other tumours have been reported in post-marketing surveillance, and spironolactone has shown tumor-forming potential in animal studies.
• Seek urgent medical attention for muscle weakness with an irregular heartbeat, unusual bruising or bleeding, yellowing of the skin or eyes, severe skin blistering or peeling, or signs of a severe allergic reaction.

• Use with caution in patients with impaired kidney function, since minor changes in fluid and electrolyte balance can be significant and severe impairment is contraindicated.
• Use with caution in patients with impaired liver function, since electrolyte shifts can trigger hepatic coma, and dosage may need to be reduced as diuresis progresses in cirrhosis.
• Use with caution in patients also taking other medications that raise potassium levels, such as ACE inhibitors, ARBs, or NSAIDs.
• Use with caution in patients with diabetes or other conditions requiring close electrolyte monitoring.
• Use with caution when driving or operating machinery, since drowsiness and dizziness can occur, particularly when starting treatment.
• Use with caution in older adults and in patients with pre-existing kidney impairment, who are more likely to develop an elevated BUN on treatment.

• Contraindicated in patients with known hypersensitivity to spironolactone or any ingredient in the tablet.
• Contraindicated in patients with anuria (absence of urine production).
• Contraindicated in patients with Addison's disease.
• Contraindicated in patients with acute kidney insufficiency or severe kidney impairment (GFR under 30 mL/min/1.73 m²).
• Contraindicated in patients with hyperkalemia.
• Contraindicated during pregnancy.
• Contraindicated during breastfeeding.
• Contraindicated in combination with eplerenone.
• Contraindicated in combination with heparin or low molecular weight heparin.
• Contraindicated in combination with mitotane.

• ACE inhibitors, angiotensin II receptor blockers, and NSAIDs used together with spironolactone increase the risk of hyperkalemia.
• Spironolactone increases the half-life of digoxin, which can raise digoxin blood levels and the risk of digitalis toxicity, so the digoxin dose may need to be reduced.
• Lithium should generally not be combined with spironolactone or other diuretics, since spironolactone reduces the kidney's clearance of lithium and increases the risk of lithium toxicity.
• Combining spironolactone with other diuretics or antihypertensive drugs has an additive blood-pressure-lowering effect, and doses of ganglionic blocking agents in particular may need to be reduced by at least half.
• Corticosteroids and ACTH can intensify potassium loss (hypokalemia) when combined with spironolactone.
• Cholestyramine or ammonium chloride combined with spironolactone has been linked to hyperchloremic metabolic acidosis, often with hyperkalemia.
• Alcohol, barbiturates, and narcotics may increase the risk of a drop in blood pressure on standing (orthostatic hypotension), especially when starting spironolactone.
• NSAIDs such as ASA, mefenamic acid, and indomethacin may reduce the diuretic effect of spironolactone; indomethacin combined with potassium-sparing diuretics has also been linked to hyperkalemia.
• Spironolactone reduces the blood vessels' responsiveness to norepinephrine, which is relevant if regional or general anesthesia is planned.
• Combining spironolactone with mitotane is contraindicated, since spironolactone can block mitotane's action against adrenal cancer.
• Combining spironolactone with eplerenone or with heparin/low molecular weight heparin is contraindicated due to the risk of severe hyperkalemia.

• Spironolactone should be taken with food: food increases its absorption significantly, roughly doubling blood levels compared with taking it on an empty stomach, so taking it consistently with meals helps ensure a reliable effect.
• Avoid potassium-rich foods and salt substitutes, such as bananas, oranges, prunes, raisins, and orange juice, while taking spironolactone, as these can add to the risk of high blood potassium.

• Spironolactone is usually taken once daily or in divided doses with meals, at consistent times each day, to support steady absorption and reduce stomach upset.

• Store spironolactone tablets at 15°C to 25°C, away from heat and moisture.

• Spironolactone can raise blood potassium levels, so avoid potassium supplements, salt substitutes, and high-potassium foods unless your doctor specifically tells you otherwise.
• Regular blood tests to check kidney function and potassium levels are an important part of spironolactone treatment.
• Tell your doctor about muscle weakness, an irregular heartbeat, unusual breast changes, or new skin rash while taking spironolactone.