spironolactone (Aldactone)

Dosing and uses of Aldactone (spironolactone)

• Adult
• Pediatric
• Geriatric

 

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%)