Spironolactone oral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations of spironolactone.
Drugs List
Therapeutic Indications
Uses
Ascites - malignant
Ascites and oedema associated with hepatic cirrhosis
Congestive heart failure
Hyperaldosteronism - primary: diagnosis
Hyperaldosteronism - primary: treatment
Nephrotic syndrome
New York Heart Association Class III failure
New York Heart Association Class IV failure
Unlicensed Uses
Hypokalaemia induced by diuretics or amphotericin in children
Resistant hypertension
Dosage
Adults
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.
Elderly
It is recommended that treatment be started at the lowest dose and titrated upwards as required to achieve maximum benefit (See Dosage; Adult).
Care should be taken with severe hepatic and renal impairment which may alter drug metabolism and excretion.
Children
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.
Neonates
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.
Patients with Renal Impairment
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.
Contraindications
Acute porphyria
Acute renal failure
Addison's disease
Anuria
Galactosaemia
Hyperkalaemia
Moderate renal impairment in children under 18 years
Severe renal impairment
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.
Antiandrogenic effects have been seen in humans and feminization in male rat foetuses has been observed with spironolactone. In one study, rat offspring of both sexes exposed in utero in late gestation exhibited permanent dose related changes in their reproductive tracts. In animal experiments carcinogenic effects have been seen, although as yet, there are no indications of any clinical relevance of this finding to humans. No reports associating spironolactone to congenital defects (cardiovascular defects, spina bifida, polydactyly, limb reduction defects and hypospadias) in human pregnancies have been found (Briggs, 2011).
Diuretics are not recommended for use during pregnancy because of theoretical concerns that they may further reduce the circulatory blood volume in women with pre-eclampsia. If therapy is essential, the development of oligohydramnios should be ruled out in long term treatment. Hypoglycaemia in the newborn should also be determined. Schaefer (2007) concludes that therapy with a diuretic is not an indication for interrupting the pregnancy.
The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Lactation
Use spironolactone with caution in breastfeeding.
It is not known whether unmetabolised spironolactone is excreted into breast milk. Canrenone, which is the principle metabolite, is excreted into human milk and has been found with a milk: plasma ratio of 0.72 at 2 hours, and 0.51 at 14.5 hours. These amounts would provide an estimated maximum of 0.2% of the mother's daily dose to the infant, Briggs (2011) consider these amounts to be clinically insignificant. The effects of spironolactone on the nursing infant are unknown. Theoretically, intense diuresis could suppress lactation, however, spironolactone alone is unlikely to produce this effect. Schaefer (2007) concludes spironolactone should be used only for special indications, such as primary hyperaldosteronism, ascites and nephrotic syndrome.
Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1
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
Effects on Laboratory Tests
Spironolactone has been reported to interfere with certain digoxin assays. Patients who are receiving spironolactone should have their serum digoxin concentrations measured by means other than serum digoxin concentrations, unless the digoxin assay has been proven not to be affected by spironolactone therapy.
In fluorometric assays, spironolactone may interfere with the estimation of compounds with similar fluorescence characteristics.
Overdosage
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Further Information
Last Full Review Date: March 2016
Reference Sources
Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.
Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.
The Renal Drug Handbook. Fourth Edition (2014) ed. Ashley, C and Dunleavy, A, Radcliffe Publishing Ltd, London.
Summary of Product Characteristics: Aldactone 25mg tablets. Pfizer Ltd. Revised February 2016.
Summary of Product Characteristics: Aldactone 50mg tablets. Pfizer Ltd. Revised February 2016.
Summary of Product Characteristics: Aldactone 100mg tablets. Pfizer Ltd. Revised February 2016.
Summary of Product Characteristics: Spironolactone Film-coated Tablets 12.5mg. ADVANZ Pharma. Revised October 2020.
Summary of Product Characteristics: Spironolactone Tablets 25mg. Actavis UK Ltd. Revised June 2014.
Summary of Product Characteristics: Spironolactone Tablets 50mg. Actavis UK Ltd. Revised June 2014.
Summary of Product Characteristics: Spironolactone Tablets 100mg. Actavis UK Ltd. Revised June 2014.
Summary of Product Characteristics: Spironolactone Tablets 25mg. Kent Pharmaceuticals Ltd. Revised February 2012.
Summary of Product Characteristics: Spironolactone Tablets 100mg. Kent Pharmaceuticals Ltd. Revised February 2012.
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 10 March 2021
The Drug Database for Acute Porphyria (NAPOS).
Available at: https://www.drugs-porphyria.org/
Spironolactone Last revised: 16 April, 2010
Last accessed: 9 March, 2016
US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Spironolactone Last revised: August 1, 2013
Last accessed: 10 March, 2015
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
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