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Hypertension in CKD Pregnancy: Contraindicated — antiandrogenic effects may cause feminisation of male fetus. Avoid throughout pregnancy.

Spironolactone (Resistant Hypertension in CKD)

Brand names: Aldactone

Adult dose

Dose: 25 mg once daily; titrate to 50 mg OD (resistant hypertension). Maximum 100-200 mg/day for primary hyperaldosteronism.
Route: Oral
Frequency: Once daily
Max: 50 mg/day for resistant hypertension in CKD (higher doses not recommended)
Steroidal mineralocorticoid receptor antagonist. PATHWAY-2 trial: most effective 4th-line antihypertensive for resistant hypertension. Use with EXTREME CAUTION in CKD — hyperkalaemia risk increases significantly with eGFR <45. Avoid if eGFR <30.

Paediatric dose

Dose: 1-3 mg/day/kg
Route: Oral
Frequency: Once to twice daily
Max: 100 mg/day
Used in paediatric heart failure and primary hyperaldosteronism. BNFc for specific dosing.

Dose adjustments

Renal

eGFR 30-44: start 25 mg and monitor K+ closely (weekly for 4 weeks). eGFR <30: AVOID — very high hyperK risk. Caution with any potassium-raising co-medication (ACEi, ARB, NSAIDs, trimethoprim).

Hepatic

No dose adjustment needed; can be used in hepatic cirrhosis with ascites (different dose regimen — GI/hepatology section)

Paediatric weight-based calculator

Used in paediatric heart failure and primary hyperaldosteronism. BNFc for specific dosing.

Clinical pearls

  • PATHWAY-2 trial (Williams et al. Lancet 2015): spironolactone (25-50 mg) vs bisoprolol vs doxazosin vs placebo as 4th-line add-on in resistant hypertension — spironolactone SUPERIOR for BP lowering at 12 weeks. Established as the preferred 4th-line agent.
  • Resistant hypertension = uncontrolled BP on 3 agents (including a diuretic) at optimal doses. Before adding spironolactone, confirm true resistance (rule out white-coat hypertension, medication non-adherence, secondary hypertension).
  • Gynaecomastia: dose-related and more common with higher doses. If bothersome, switch to eplerenone (more selective MR antagonist, fewer androgen effects) or finerenone.
  • The hyperK danger zone: spironolactone + ACEi/ARB + CKD = triple threat for hyperkalaemia. K+ must be checked at baseline, 1 week, 1 month, and 3-monthly thereafter. If K+ >5.5 mmol/L — halve dose. If >6.0 mmol/L — stop immediately.
  • RALES trial: spironolactone in heart failure with reduced EF (HFrEF) — 30% reduction in mortality. However, this is a different indication from resistant hypertension — see cardiology section.

Contraindications

  • eGFR <30 mL/min
  • Potassium >5.0 mmol/L
  • Addison's disease
  • Concomitant eplerenone or finerenone
  • Hypersensitivity to spironolactone

Side effects

  • Hyperkalaemia (most dangerous — potentially fatal)
  • Gynaecomastia (steroidal structure — cross-reacts with androgen receptor; dose-related)
  • Menstrual irregularities
  • Impotence/decreased libido
  • Breast tenderness
  • Hyponatraemia
  • Postural hypotension

Interactions

  • ACEi/ARBs — additive hyperK; frequent monitoring essential in CKD
  • NSAIDs — blunt diuretic effect + additive nephrotoxicity + additive hyperK
  • Trimethoprim — additive hyperK (trimethoprim blocks distal K+ secretion)
  • Digoxin — spironolactone increases digoxin levels; monitor digoxin
  • Lithium — spironolactone increases lithium toxicity risk

Monitoring

  • Potassium (baseline, 1 week, 1 month, then 3-monthly)
  • eGFR (baseline and 1 month)
  • Blood pressure
  • Gynaecomastia/sexual side effects

Reference: BNFc; BNF 90; PATHWAY-2 Trial (Williams et al. Lancet 2015); RALES Trial (Pitt et al. NEJM 1999); NICE NG136 (Hypertension); SPC Aldactone. Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.

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