Congestive heart failure

Initial dose: 100mg in single or divided doses.
Usual maintenance dosage: 25mg to 200mg once daily.

 

Alternatively, in moderate to severe heart failure (adjunct), give 25mg once daily initially. Titrate to response, up to maximum 50mg once daily.

 

Severe heart failure (New York Heart Association Class III to IV)

Initial dose: 25mg once daily if serum potassium is less than or equal to 5mEq/l and serum creatinine is less than or equal to 2.5mg/dl.
Patients who tolerate 25mg once daily may have their dose increased to 50mg once daily as clinically indicated. Patients who do not tolerate 25mg once daily may have their dose reduced to 25mg every other day.

 

 

Ascites and oedema associated with hepatic cirrhosis

If urinary Na+/K+ ratio is greater than 1, give 100mg daily. If the ratio is less than 1, give 200mg to 400mg daily.

 

 

Ascites - malignant

Initial dose: 100mg to 200mg per day. Gradually increase up to 400mg once daily in severe cases. When oedema is controlled, maintenance dosage should be individually determined.

 

 

Nephrotic syndrome

100mg to 200mg daily.
Spironolactone has not been shown to be anti-inflammatory, nor to affect the basic pathological process. Its use is only advised if glucocorticoids by themselves are insufficiently effective.

 

 

Diagnosis and treatment of

primary aldosteronism

Long test: 400mg spironolactone is administered daily for three to four weeks. Correction of hypokalaemia and of hypertension provides presumptive evidence for the diagnosis of primary hyperaldosteronism.
Short test: 400mg spironolactone is administered daily for four days. If serum potassium increases during administration but drops when discontinued, a presumptive diagnosis of primary hyperaldosteronism should be considered.

 

After diagnosis of hyperaldosteronism has been established by more definitive testing, spironolactone may be administered at doses of 100mg to 400mg daily in preparation for surgery. For patients who are unsuitable for surgery spironolactone may be employed for long term maintenance therapy at the lowest effective dosage for the individual patient.

 

Resistant hypertension (adjunct) (unlicensed)

25mg once daily.

 

Initial dose: 1mg/kg to 3mg/kg given in divided doses. Titrate to response and tolerance. If necessary, the tablets may be crushed to make a suspension. Treatment to be given under specialist guidance.

 

Nephrotic syndrome; Oedema in heart failure and in ascites

Children aged 12 to 18 years: 50mg to 100mg daily in one single or two divided doses. Consider up to 9mg/kg daily (maximum 400mg daily) in resistant ascites.
Children aged 1 month to 12 years: 1mg/kg to 3mg/kg daily in one single or two divided doses. Consider up to 9mg/kg daily in resistant ascites.

 

 

Reduction of hypokalaemia induced by diuretics or amphotericin (unlicensed)

Children aged 12 to 18 years: 50mg to 100mg daily in one single or two divided doses. Consider up to 9mg/kg daily (maximum 400mg daily) in resistant ascites.
Children aged 1 month to 12 years: 1mg/kg to 3mg/kg daily in one single or two divided doses. Consider up to 9mg/kg daily in resistant ascites.

Initial dose: 1mg/kg to 2mg/kg given in divided doses. Titrate to response and tolerance. If necessary, the tablets may be crushed to make a suspension.
Consider giving up to 7mg/kg daily in resistance ascites.

 

Nephrotic syndrome; Oedema in heart failure and in ascites

1mg/kg to 2mg/kg daily in one single or two divided doses. Consider up to 7mg/kg daily in resistant ascites.

 

 

Reduction of hypokalaemia induced by diuretics or amphotericin (unlicensed)

1mg/kg to 2mg/kg daily in one single or two divided doses. Consider up to 7mg/kg daily in

resistant ascites.

The Renal Drug Handbook suggests the following doses based on Glomerular Filtration Rate (GFR):

GFR 10 to 50ml/minute: 50% of normal dose.
GFR less than 10ml/minute: Use with caution.
Small studies have shown that doses of 25mg spironolactone three times per week can be used safely in haemodialysis patients although it is unknown whether or not this dose would have any therapeutic benefit. Potassium levels should be monitored closely.

Precautions and Warnings

Elderly
Predisposition to acidosis
Breastfeeding
Diabetes mellitus
Diabetic nephropathy
Glucose-galactose malabsorption syndrome
Hepatic impairment
Hyponatraemia
Lactose intolerance
Pregnancy
Renal impairment

Advise ability to drive/operate machinery may be affected by side effects
Not all available brands are licensed for all indications
Some formulations contain lactose
Monitor periodically for signs of fluid or electrolyte imbalance
Monitor serum creatinine
Monitor serum potassium periodically
Discontinue treatment before glucose tolerance test
May affect results of some laboratory tests
Discontinue if hyperkalaemia occurs
Carcinogenic in rats on long term use and at high doses
Advise patient not to take NSAIDs unless advised by clinician
Advise on problems of salt substitutes/high intake of potassium-rich food

Spironolactone has been found to be carcinogenic in rodents when administered at high doses over a long period of time. Long term use in young patients requires careful consideration.

Use with caution in patients with diabetic nephropathy as there is an increased risk of hyperkalaemia. Spironolactone should be discontinued at least 3 days before a glucose tolerance test because of the risk of severe hyperkalaemia in these patients.

Reversible hyperchloraemic metabolic acidosis, usually with hyperkalaemia, has been reported in patients with decompensated hepatic cirrhosis, even in the presence of normal renal function. Use with caution in patients with a predisposition to metabolic acidosis.

Hyperkalaemia in patients with severe heart failure
Avoid using oral potassium supplements in patients with serum potassium greater than 3.5 mEq/l. The recommended monitoring for potassium and creatinine is 1 week after initiation or increase in dose of spironolactone, monthly for the first 3 months, then quarterly for a year, and then every 6 months.

Pregnancy and Lactation

Pregnancy

Use spironolactone with caution in pregnancy.

Diuretics are no longer used as standard therapy during pregnancy and should only be used for particular indications. Spironolactone should only be chosen if therapy with an aldosterone antagonist is absolutely necessary.

Lactation

Use spironolactone with caution in breastfeeding.

 

Side Effects

Abdominal cramps
Acute renal failure
Agranulocytosis
Alopecia
Arrhythmias
Ataxia
Benign breast neoplasm
Blood disorders
Blood urea increased
Breast pain
Changes in hepatic function
Changes in libido
Clumsiness
Confusion
Diarrhoea
Dizziness
Drowsiness
Drug rash with eosinophilia and systemic symptoms (DRESS)
Electrolyte disturbances
Eosinophilia
Female type hair growth
Gastritis
Gastro-intestinal symptoms
Gastro-intestinal ulceration and bleeding
Gynaecomastia
Headache
Hepatotoxicity
Hyperkalaemia
Hypersensitivity reactions
Hypertrichosis
Hyponatraemia
Impotence
Increase in blood urea nitrogen
Leg cramps
Lethargy
Leukopenia
Malaise
Menstrual disturbances
Metabolic acidosis
Muscle spasm
Nausea
Osteomalacia
Paralysis
Paraplegia
Pemphigoid reaction
Pruritus
Rash
Sexual dysfunction
Shock
Shortness of breath
Stevens-Johnson syndrome
Sweating
Swelling
Syncope
Thrombocytopenia
Toxic epidermal necrolysis
Urticaria
Voice changes
Vomiting