spironolactone (Aldactone)
Classes: Aldosterone Antagonists, Selective; Diuretics, Potassium-Sparing
Dosing and uses of Aldactone (spironolactone)
Adult dosage forms and strengths
tablet
- 25mg
- 50mg
- 100mg
Primary Hyperaldosteronism
As a diagnostic agent
- Long test: 400 mg PO qDay for 3-4 weeks
- Short test: 400 mg PO qDay for 4 days
Short-term perioperative treatment for adrenalectomy
- Initial: 100-400 mg PO qDay in preparation for surgery
- Maintenance: Lowest effective dose individualized for patient
Edematous Conditions
Cirrhosis of the liver with edema and/or ascites; nephrotic syndrome
Initial: 100 mg qDay or divided q12hr for 5 days; if no clinical response, add second diuretic with more specific mechanism of action
Range: 25-200 mg PO qDay or divided q12hr
Essential Hypertension
Initial: 25-100 mg PO qDay or divided q12hr for >2 weeks; adjust to patient response
Congestive Heart Failure
Indicated for NYHA class II/IV heart failure (provided CrCl >30 mL/min and serum K <5 mEq/dL)
Initial: 25 mg PO qDay
Range: 12.5-25 mg/day PO; may increase to 50 mg/day if needed; if 25 mg/day not tolerated, reduce to 25 mg every other day
ACC/AHA guidelines recommend aldosterone antagonist to be added to an ACEI or ARB, plus a beta blocker; patient conditions may also require additional medications (eg, loop diuretics, hydralazine, nitrates, digoxin)
Hypokalemia
Range: 25-100 mg PO qDay
Hirsutism (Off-label)
Women with hirsutism
50-200 mg PO qDay or divided q12hr
Acne (Off-label)
Females with hormonal acne
50-200 mg PO qDay or divided q12hr
Dosing Modifications
Renal impairment
- CrCl ≥50 mL/min/1.73 m²: 12.5-25 mg qDay; use maintenance dose of 25 mg qDay or q12hr after 4 weeks of treatment with potassium ≤5 mEq/L
- CrCl 30-49 mL/min/1.73 m²: 12.5 mg qDay or every other day; use maintenance dose of 12.5-25 mg qDay after 4 weeks of treatment with potassium ≤5 mEq/L
- CrCl <30 mL/min/1.73 m²: Avoid use
Overdose Management
May use normal saline for volume replacement
May use dopamine or norepinephrine to treat hypotension
Treat hyperkalemia with IV glucose (dextrose 25% in water), concurrently with rapid-acting insulin and IV sodium bicarbonate; oral/rectal solutions of Kayexalate in sorbitol can be used if needed
If dysrhythmia due to decreased K+ or Mg+ suspected, replace aggressively
Discontinue treatment if no symptoms after 6 hr
Pediatric dosage forms and strengths
tablet
- 25mg
- 50mg
- 100mg
Edema (Off-label)
CHF, cirrhosis, ascites, and nephrotic syndrome
1-3.3 mg/kg/day PO or divided q12hr; not to exceed 3.3 mg/kg/day or up to 100 mg/day
Hypertension (Off-label)
Among therapeutic options recommended by the National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents
1-3.3 mg/kg/day PO or divided q12hr; not to exceed 3.3 mg/kg/day or up to 100 mg/day
Hyperaldosteronism (Orphan)
Orphan designation for primary hyperaldosteronism
Sponsor
- CMP Pharma, Inc; PO Box 147, 8026 US Highway 264A; Farmville, NC 27828
Geriatric dosage forms and strengths
Diuresis
12.5 mg PO qDay in 1-2 divided doses; increase by 25-50 mg q5Days PRN; adjust for renal impairment
Hyperaldosteronism
Initial: 400 mg/day PO, THEn
100-300 mg/day
Congestive heart failure
Indicated for NYHA class II/IV heart failure (provided CrCl >30 mL/min and serum K <5 mEq/dL)
Initial: 25 mg PO qDay
Range: 12.5-25 mg/day PO; may increase to 50 mg/day if needed; if 25 mg/day not tolerated, reduce to 25 mg every other day
ACC/AHA guidelines recommend aldosterone antagonist to be added to an ACEI or ARB, plus a beta blocker; patient conditions may also require additional medications (eg, loop diuretics, hydralazine, nitrates, digoxin)
Dosing considerations
Caution with heart failure and avoid with CrCl <30 mL/min (Beers criteria)
In heart failure, the risk of hyperkalemia is higher in older adults, especially if taking >25 mg/day or with concomitant NSAID, ACE inhibitor, ARB, or potassium supplement
Aldactone (spironolactone) adverse (side) effects
Frequency not defined
Drowsiness
Lethargy
Headache
Mental confusion
Rash
Urticaria
Stevens-Johnson syndrome, toxic epidermal necrolysis
Drug rash with eosinophilia and systemic symptoms (DRESS)
Gynecomastia
Impotence
Menstrual disorders
Abdominal cramping
Diarrhea
Gastritis
Nausea
Vomiting
Breast pain
Leukopenia
Electrolyte disturbances
Leg cramps
Dizziness
Alopecia
Pruritus
Warnings
Black box warnings
Spironolactone has been shown to be a tumorigen in chronic toxicity studies in rats; use only for specified indications
Contraindications
Hypersensitivity
Anuria
Severe renal impairment, acute renal insufficiency
Addison’s disease or other conditions associated with hyperkalemia
Coadministration with eplerenone
Cautions
Use caution in diabetes mellitus, diabetic nephropathy, fluid and electrolyte imbalance, hepatic disease, metabolic acidosis
Concomitant use with K+-sparing diuretics or ACE inhibitors
If used for edema alone, maintain initial dose for at least 5 days before adjustments
Avoid potassium-rich diet or supplements
Monitor serum potassium; severe hyperkalemia may occur with concomitant use with other potassium-sparing diuretics, or ACE inhibitors, angiotensin II antagonists, NSAIDs, heparin, LMWH, potassium supplements, salt substitutes, or other drugs known to cause hyperkalemia
Risk of potentially fatal hyperkalemia in severe heart failure patients
Discontinue if hyperkalemia develops
Hyperkalemic metabolic acidosis has been reported in patients given spironolactone concurrently with cholestyramine
Risk of gynecomastia and male sexual dysfunction
Not recommended for pregnancy-induced hypertension
In cirrhosis, avoid electrolyte and acid/base imbalances that might lead to hepatic encephalopathy
Somnolence may occur; caution when operating heavy machinery
Excess amounts of electrolyte loss can result in profound diuresis; adjust to avoid dehydration; correct electrolyte disturbances resulting from therapy
Discontinue use prior to adrenal vein catherization
Risk of hyperkalemia increases with declining renal function
Risk of orthostasis may occur with oncurrent ethanol use
Pregnancy and lactation
Pregnancy category: C
Lactation: Metabolite excreted into breast milk; discontinue breastfeeding or do not use drug
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.
Pharmacology of Aldactone (spironolactone)
Mechanism of action
Aldosterone antagonist with diuretic and antihypertensive effects; competitive binding of receptors at aldosterone-dependent Na-K exchange site in distal tubules results in increased excretion of Na+, Cl-, and H2O and retention of K+ and H+
Increases testosterone clearance and estradiol production; blocks conversion of potent androgens to weaker ones in peripheral tissues
Absorption
Increased with food
Bioavailability: 73%
Onset: 2-4 hr
Duration: 2-3 days
Peak serum time: 3-4 hr
Distribution
Protein bound: 90%
Metabolism
Metabolized by the liver and kidneys
Metabolites: Canrenone, 7-alpha-thiomethylspirolactone, 6-beta-hydroxy-7-alpha-thiomethylspirolactone (active)
Elimination
Half-life: Parent drug (1.3-1.4 hr); metabolite [canrenone] (9-23 hr)
Excretion: Urine (47-57%); feces (35-41%)
