Spironolactone Side Effects: A Comprehensive Guide

Spironolactone is a potassium-sparing diuretic with anti-androgen properties. Its side effect profile reflects both of these mechanisms.

Side effects affecting more than 1 in 10 people:

• Hyperkalaemia (elevated blood potassium): the most clinically significant side effect, requiring regular monitoring

Side effects affecting 1 in 10 to 1 in 100 people:

• Breast tenderness and gynaecomastia (breast tissue enlargement): occurs in both men and women due to the anti-androgen effect. In men, this is often the most bothersome side effect
• Menstrual irregularities: including irregular periods, heavy bleeding or amenorrhoea (absence of periods) in pre-menopausal women
• Dizziness and light-headedness: particularly when standing up quickly (postural hypotension), as spironolactone lowers blood pressure
• Nausea and gastrointestinal upset: usually mild and often settle with continued use
• Fatigue and drowsiness: may improve over the first few weeks
• Headache: generally transient

These side effects are largely dose-dependent. At lower doses (25 to 50 mg), side effects are less frequent and less severe. At higher doses (100 to 200 mg), they become more common.

Your prescriber will usually start at the lowest effective dose and increase gradually.

Hyperkalaemia (potassium level above 5.5 mmol/L) is the most serious potential side effect of spironolactone and can be life-threatening if undetected.

Why spironolactone causes high potassium:

• Spironolactone blocks aldosterone, which normally promotes potassium excretion by the kidneys
• By blocking aldosterone, spironolactone causes the kidneys to retain more potassium

Risk factors for hyperkalaemia:

• Renal impairment (even mild)
• Concomitant use of ACE inhibitors, ARBs, potassium supplements, NSAIDs or trimethoprim
• Diabetes mellitus (due to impaired renal potassium excretion)
• Older age
• Dehydration or acute illness

Symptoms of hyperkalaemia:

• Muscle weakness or heaviness in the legs
• Palpitations or irregular heartbeat
• Nausea
• Tingling or numbness
• In severe cases: cardiac arrhythmias, which can be fatal

Monitoring requirements:

• The BNF recommends checking renal function and electrolytes before starting, at 1 week, at 4 weeks, and then at 3-monthly intervals for the first year
• If the dose is changed or an interacting medicine is added, electrolytes should be rechecked within 1 week
• You should avoid potassium-rich salt substitutes (e.g. Lo-Salt) while taking spironolactone

If a blood test shows hyperkalaemia, your prescriber may reduce the dose, stop the medicine, or adjust other medications.

Spironolactone has significant anti-androgen activity, which is therapeutically useful in some conditions (such as acne, hirsutism and androgenetic alopecia in women) but can cause unwanted effects in others.

In women:

• Menstrual irregularities: the most commonly reported hormonal effect. Periods may become irregular, heavier, lighter or stop altogether
• Breast tenderness: common, particularly at higher doses
• Reduced libido: reported by some women, though others notice no change
• Skin changes: some women notice improved skin and reduced acne (this is often the reason it is prescribed for dermatological conditions)

In men:

• Gynaecomastia (breast enlargement): occurs in approximately 10% of men at doses above 50 mg. It can be uncomfortable and may not fully resolve after stopping the medicine
• Breast tenderness: may precede or accompany gynaecomastia
• Erectile dysfunction: reported uncommonly
• Reduced libido: more common at higher doses

These effects are due to spironolactone blocking androgen receptors and increasing the conversion of testosterone to oestradiol.

They are reversible on stopping the medicine in most cases, though gynaecomastia that has been present for a prolonged period may not fully resolve.

If anti-androgen effects are problematic, your prescriber may consider switching to eplerenone, a newer aldosterone antagonist with fewer hormonal side effects.

The following side effects are less frequently reported but should be noted:

Uncommon:

• Skin rash or pruritus
• Confusion or difficulty concentrating
• Leg cramps (which may be related to electrolyte changes)
• Deepening of the voice (in women, at high doses)

Rare:

• Hepatotoxicity: very rare reports of liver inflammation. The BNF advises discontinuation if hepatic impairment worsens
• Agranulocytosis: extremely rare but serious blood disorder
• Stevens-Johnson syndrome: very rare hypersensitivity reaction
• Hyponatraemia (low sodium): can occur, particularly in combination with other diuretics

Metabolic effects:

• Spironolactone may cause a mild metabolic acidosis
• It can increase uric acid levels, which may be relevant for patients with gout

The overall safety record of spironolactone is good when used with appropriate monitoring. It has been in clinical use since the 1960s and its side effect profile is well characterised.

Report any unusual symptoms to your prescriber and via the Yellow Card Scheme.

Most spironolactone side effects can be minimised with the right approach.

Reducing dizziness:

• Stand up slowly from sitting or lying positions
• Stay well hydrated (but avoid excessive fluid intake, as this can worsen oedema)
• If dizziness persists, your prescriber may review your blood pressure medication regimen

Managing breast tenderness:

• Wearing a supportive, well-fitting bra (or compression garment in men) can help
• Dose reduction often improves this symptom
• If gynaecomastia is distressing, discuss switching to eplerenone with your prescriber

Menstrual irregularities:

• These usually stabilise after 2 to 3 months
• If bleeding is heavy or prolonged, your prescriber may adjust the dose or add a hormonal contraceptive

Preventing hyperkalaemia:

• Attend all scheduled blood tests
• Avoid potassium supplements and potassium-rich salt substitutes
• Stay hydrated, especially during hot weather or illness
• Report diarrhoea, vomiting or reduced fluid intake to your prescriber, as these can precipitate electrolyte disturbance

General advice:

• Take spironolactone with food to reduce gastrointestinal side effects
• Take it in the morning to reduce the impact of increased urination on sleep
• Do not stop the medicine abruptly without medical advice, especially if you are taking it for heart failure