Usage
Spironolactone is prescribed for various medical conditions, including:
- Heart failure: Reduces morbidity and mortality in moderate to severe heart failure.
- Hypertension (high blood pressure): Used as an add-on therapy to lower blood pressure when other treatments are not sufficient.
- Edema (fluid retention): Manages edema caused by conditions such as cirrhosis, nephrotic syndrome, and heart failure.
- Primary hyperaldosteronism: Used in diagnosis and treatment.
- Hypokalemia (low potassium levels): Used when oral potassium supplements are not suitable.
- Hirsutism (excess hair growth in women): Off-label use to manage excessive hair growth.
- Premenstrual Syndrome (PMS): Off-label use for PMS symptom management.
- Acne: Off-label use in certain cases of acne, particularly hormonal acne.
Pharmacological Classification: Potassium-sparing diuretic, aldosterone receptor antagonist.
Mechanism of Action: Spironolactone competitively inhibits the binding of aldosterone to its receptors in the distal convoluted tubule of the kidneys. This reduces sodium reabsorption, leading to increased excretion of sodium and water, while conserving potassium.
Alternate Names
- International Nonproprietary Name (INN): Spironolactone
- Brand Names: Aldactone, CaroSpir
How It Works
Pharmacodynamics: Spironolactone acts as a competitive antagonist of aldosterone at the mineralocorticoid receptor in the distal convoluted tubule. By blocking aldosterone’s effects, spironolactone promotes natriuresis (sodium excretion) and diuresis (water excretion) while preventing potassium loss. It also has weak antiandrogenic effects, which may be beneficial in managing hirsutism.
Pharmacokinetics:
- Absorption: Well-absorbed orally. Food may enhance absorption.
- Metabolism: Extensively metabolized in the liver, primarily to canrenone and 7α-thiomethylspironolactone, which are active metabolites.
- Elimination: Primarily excreted renally (via the kidneys) and to a lesser extent through feces.
Mode of Action: Spironolactone binds competitively to the mineralocorticoid receptor, preventing aldosterone from binding and exerting its effects on sodium and potassium channels in the distal renal tubule. This leads to decreased sodium reabsorption and potassium secretion.
Receptor Binding: Mineralocorticoid receptor antagonist.
Enzyme Inhibition/Neurotransmitter Modulation: No significant enzyme inhibition or neurotransmitter modulation known.
Elimination Pathways: Primarily renal excretion of metabolites. Some hepatic metabolism via CYP450 enzymes.
Dosage
Standard Dosage
Adults:
The dosage varies depending on the indication:
- Heart failure: Initial dose: 25 mg once daily, titrated up to 50 mg/day as needed.
- Hypertension: 25–100 mg/day, given in a single dose or divided doses.
- Edema: 100 mg/day, may range from 25–200 mg/day.
- Primary hyperaldosteronism: 100-400 mg/day.
Children:
- Edema: 1–3.3 mg/kg/day in divided doses, maximum 3.3 mg/kg/day or 100 mg/day, whichever is lower. Use under pediatric specialist guidance.
- Other pediatric uses are considered off-label, and dosage should be determined by a pediatrician based on weight, age, and the specific condition being treated.
Special Cases:
- Elderly Patients: Start with a lower dose (e.g., 12.5 mg/day) and titrate slowly based on response and tolerance.
- Patients with Renal Impairment: Dose adjustment needed based on the severity of impairment. Close monitoring of potassium levels is essential. Contraindicated in severe renal impairment.
- Patients with Hepatic Dysfunction: Dose reduction may be necessary.
- Patients with Comorbid Conditions: Caution is advised in patients with diabetes, as spironolactone can exacerbate hyperkalemia.
Clinical Use Cases
Spironolactone is not typically used in clinical settings such as intubation, surgical procedures, mechanical ventilation, or emergency situations like cardiac arrest. Its primary use is in chronic conditions such as heart failure, hypertension, and edema.
Dosage Adjustments
Dose adjustments are necessary based on renal function, hepatic function, electrolyte imbalances, and other medications the patient is taking. Serum potassium levels should be closely monitored, especially in the initial phase of treatment and with dosage changes.
Side Effects
Common Side Effects:
- Hyperkalemia (high potassium)
- Gynecomastia (breast enlargement in men)
- Breast tenderness
- Menstrual irregularities
- Dizziness
- Fatigue
- Headache
- Gastrointestinal disturbances (nausea, vomiting, diarrhea)
Rare but Serious Side Effects:
- Severe hyperkalemia (life-threatening)
- Hyponatremia (low sodium)
- Dehydration
- Acute renal failure (rare)
- Liver dysfunction (rare)
Long-Term Effects:
- Gynecomastia (may be persistent)
Adverse Drug Reactions (ADR):
- Hyperkalemia requiring urgent medical attention
- Electrolyte imbalances (e.g., hyponatremia, hypomagnesemia)
Contraindications
- Hyperkalemia
- Addison’s disease
- Anuria (lack of urine output)
- Severe renal impairment
- Concomitant use of eplerenone
Drug Interactions
- Potassium supplements or salt substitutes containing potassium (increased risk of hyperkalemia).
- ACE inhibitors, ARBs, and other potassium-sparing diuretics (risk of hyperkalemia).
- NSAIDs (can reduce the effectiveness of spironolactone and increase the risk of hyperkalemia).
- Digoxin (spironolactone can increase digoxin levels).
- Lithium (spironolactone can increase lithium levels).
- Certain medications metabolized by the liver (e.g., some antibiotics and antifungals).
- Alcohol (can enhance some side effects).
Pregnancy and Breastfeeding
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Pregnancy Safety Category: Category C (animal studies have shown adverse effects on the fetus, and there are no adequate and well-controlled studies in pregnant women, but potential benefits may warrant use of the drug in pregnant women despite potential risks.) As of 2018, the FDA removed the letter categories for pregnancy safety. Spironolactone is generally avoided during pregnancy, especially in the first trimester, due to the risk of feminization of male fetuses.
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Breastfeeding: Small amounts of spironolactone may be excreted in breast milk. Although generally considered acceptable during breastfeeding, monitor the infant for potential side effects.
Drug Profile Summary
- Mechanism of Action: Aldosterone receptor antagonist, potassium-sparing diuretic.
- Side Effects: Hyperkalemia, gynecomastia, breast tenderness, menstrual irregularities, dizziness, fatigue.
- Contraindications: Hyperkalemia, Addison’s disease, anuria, severe renal impairment, concomitant use of eplerenone.
- Drug Interactions: Potassium supplements, ACE inhibitors, NSAIDs, digoxin, lithium.
- Pregnancy & Breastfeeding: Generally avoided during pregnancy. Acceptable during breastfeeding with monitoring.
- Dosage: Varies based on indication; 25-400 mg/day for adults.
- Monitoring Parameters: Serum potassium, creatinine, and electrolytes.
Popular Combinations
- Heart failure: Often combined with ACE inhibitors, beta-blockers, and loop diuretics.
- Hypertension: Combined with other antihypertensive medications, such as thiazide diuretics, ACE inhibitors, or calcium channel blockers.
Precautions
- Monitor potassium levels regularly.
- Caution in patients with renal or hepatic impairment.
- Avoid potassium supplements or salt substitutes containing potassium.
- Caution in patients with diabetes.
- Monitor for signs of gynecomastia.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Spironolactone?
A: The dosage varies depending on the condition being treated: Heart Failure: 25 mg/day initially, may be increased to 50mg/day. Hypertension: 25-100 mg/day. Edema: 100 mg/day (range 25-200mg/day).
Q2: What are the most common side effects of Spironolactone?
A: Hyperkalemia, gynecomastia, breast tenderness, menstrual irregularities.
Q3: Is Spironolactone safe during pregnancy?
A: Generally avoided during pregnancy, especially in the first trimester, due to the risk of fetal harm.
Q4: Can Spironolactone be used in children?
A: Yes, for the treatment of edema. Dosing should be determined and monitored by a pediatrician. Other uses are considered off-label.
Q5: How does Spironolactone interact with other medications?
A: It can interact with potassium supplements, ACE inhibitors, NSAIDs, digoxin, and lithium, among others.
Q6: What should patients be monitored for while taking Spironolactone?
A: Serum potassium, creatinine, and other electrolytes.
Q7: What are the contraindications for using Spironolactone?
A: Hyperkalemia, Addison’s disease, anuria, severe renal impairment, concomitant eplerenone use.
Q8: Can I crush Spironolactone tablets?
A: While tablets can be crushed and mixed with food or liquid for easier administration (especially for children), it’s advisable to check with a pharmacist first, as it can alter the drug’s properties.
Q9: How long does it take for Spironolactone to work?
A: The onset of action varies depending on the indication. It may take several days to weeks to see the full effect of spironolactone for edema or hypertension.
Q10: What should I do if I miss a dose of Spironolactone?
A: Take the missed dose as soon as you remember. However, if it’s almost time for your next dose, skip the missed dose and take the next dose at your regular time. Do not double the dose to catch up.
