Schedule H

Oral

Form Available Strengths

Tablets 25 mg, 50 mg, 100 mg

Oral Suspension/Syrup 5 mg/mL (select brands)

FDC with Furosemide Spironolactone 50 mg + Furosemide 20 mg

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Congestive Heart Failure (NYHA Class III–IV) — Adjunct to Standard Therapy

Parameter Recommendation

Starting dose 25 mg orally once daily

Titration Increase to 50 mg once daily after 4–8 weeks if K⁺ <5.0 mEq/L and serum creatinine <2.5 mg/dL

Usual maintenance dose 25–50 mg once daily

Maximum dose 50 mg/day (some guidelines allow up to 100 mg/day under specialist supervision)

Duration Long-term; mortality benefit demonstrated

Clinical Notes:

• Evidence-based mortality reduction in NYHA III–IV HF (RALES trial)

• Add to ACE inhibitor/ARB + beta-blocker + loop diuretic backbone

• Avoid if baseline K⁺ >5.0 mEq/L or creatinine >2.5 mg/dL

1. Resistant Hypertension (Fourth-line Agent)

Parameter Recommendation

Starting dose 25 mg orally once daily

Titration Increase by 25 mg every 2–4 weeks based on BP response

Usual maintenance dose 25–50 mg once daily

Maximum dose 100 mg/day (specialist supervision if >50 mg/day)

Clinical Notes:

• Particularly effective in low-renin hypertension and primary aldosteronism

• Check aldosterone:renin ratio before initiating if hyperaldosteronism suspected

• Synergistic effect when added to ACEi/ARB + CCB + thiazide

1. Primary Hyperaldosteronism

A) Diagnostic Testing (Short-term Aldosterone Suppression Test)

Parameter Recommendation

Dose 100–400 mg/day in divided doses

Duration 3–5 days

Note Specialist/endocrinology use only

B) Long-term Medical Management (Non-surgical candidates)

Parameter Recommendation

Starting dose 50–100 mg/day in 1–2 divided doses

Titration Adjust every 2–4 weeks based on BP and serum potassium

Usual maintenance dose 100–200 mg/day

Maximum dose 400 mg/day

Note Endocrinology specialist supervision mandatory

1. Liver Cirrhosis with Ascites

Parameter Recommendation

Starting dose 100 mg orally once daily (with furosemide 40 mg/day)

Titration Increase both drugs proportionally every 3–5 days; maintain 100:40 ratio (spironolactone:furosemide)

Usual maintenance dose 100–200 mg/day

Maximum dose 400 mg/day (with furosemide up to 160 mg/day)

Clinical Notes:

• First-line diuretic for cirrhotic ascites (secondary hyperaldosteronism)

• Aim for weight loss of 0.5 kg/day (without peripheral oedema) or 1 kg/day (with oedema)

• Monitor for encephalopathy, hyponatraemia, hyperkalaemia

• Avoid in hepatorenal syndrome (HRS) — specialist input required

1. Nephrotic Syndrome — Adjunctive Therapy

Parameter Recommendation

Starting dose 25–50 mg orally once daily

Titration Increase based on diuretic response and potassium tolerance

Usual maintenance dose 50–100 mg/day

Maximum dose 100 mg/day

Note Specialist (nephrologist) supervision advised

Clinical Notes:

• Used when response to loop diuretics is inadequate

• Aldosterone escape contributes to oedema in nephrotic syndrome

• Caution in patients with reduced GFR

1. Oedema (Generalised) — Adjunct to Loop Diuretics

Parameter Recommendation

PAEDIATRIC DOSING (Specialist Only)

Primary Indications

1. Oedema (Heart Failure, Nephrotic Syndrome, Hepatic Ascites)

Weight/Age Dose Maximum Frequency

Infants (>1 month) 1–3 mg/kg/day 3.3 mg/kg/day or 100 mg/day (whichever lower) Once daily or divided BID

Children 1–12 years 1–3 mg/kg/day 100 mg/day Once daily or divided BID

Adolescents >12 years Adult dosing 100 mg/day Once daily

Alternative calculation: 30–90 mg/m²/day

Parameter Recommendation

Starting dose 1 mg/kg/day

Titration Increase by 0.5–1 mg/kg/day every 3–5 days based on response

Usual maintenance dose 1–3 mg/kg/day

Maximum dose 3.3 mg/kg/day or 100 mg/day

1. Paediatric Heart Failure (Cardiomyopathy, Congenital Heart Disease)

Parameter Recommendation

Starting dose 1 mg/kg/day orally

Titration Increase every 5–7 days based on clinical response

Usual maintenance dose 1–3 mg/kg/day

Maximum dose 100 mg/day

Note Paediatric cardiology supervision essential

1. Bronchopulmonary Dysplasia (Neonates — NICU use)

Parameter Recommendation

Dose 1–2 mg/kg/day orally

Note NICU specialist supervision only

Secondary Indications — Paediatrics (Off-label)

Indication Age Dose Duration Notes

Congenital adrenal hyperplasia (as adjunct) >1 month 1–3 mg/kg/day Long-term OFF-LABEL; Paediatric endocrinology specialist only

Bartter syndrome >1 month 1–3 mg/kg/day Long-term OFF-LABEL; Specialist only

Paediatric Safety Notes

Parameter Recommendation

Minimum age >1 month (neonatal use only under NICU/specialist supervision)

Monitoring Serum electrolytes (K⁺, Na⁺), creatinine, weight, BP, hydration status

Frequency Baseline → 1 week after initiation → every 2–4 weeks during titration → monthly when stable

Formulation Use oral suspension for accurate dosing in infants/young children

50 No adjustment; standard dosing with routine K⁺ monitoring

30–50 Start 12.5–25 mg/day; cautious titration; monitor K⁺ every 3–5 days

15–30 Start 12.5 mg alternate days; close monitoring; avoid if K⁺ >5.0 mEq/L

<15 or Dialysis Avoid use or use only under specialist (nephrologist) supervision with intensive monitoring

Haemodialysis: Not significantly dialysed; avoid in ESRD unless specialist-directed.

Peritoneal Dialysis: Avoid; risk of severe hyperkalaemia.

Note: In cirrhotic patients, spironolactone half-life is significantly prolonged (up to 5× normal). Start low and titrate slowly.

• Hyperkalaemia (serum K⁺ >5.5 mEq/L)

• Addison's disease or primary adrenal insufficiency

• Severe renal impairment (eGFR <15 mL/min/1.73 m²) not on dialysis

• Anuria

• Known hypersensitivity to spironolactone or any excipient

• Concurrent use with eplerenone (overlapping mechanism; additive hyperkalaemia)

• Concurrent potassium supplementation (relative — avoid unless documented hypokalaemia)

• Elderly patients — increased risk of hyperkalaemia, hyponatraemia, renal impairment

• Concurrent RAAS inhibitors (ACE inhibitors, ARBs, direct renin inhibitors) — additive hyperkalaemia risk

• Diabetes mellitus, especially with nephropathy — higher hyperkalaemia risk

• Mild-to-moderate renal impairment (eGFR 30–60 mL/min) — closer monitoring needed

• Pre-existing electrolyte abnormalities

• Metabolic or respiratory acidosis — potentiates hyperkalaemia

• Long-term use — gynaecomastia, menstrual irregularities, sexual dysfunction

• Patients on digoxin — altered digoxin clearance

Parameter Recommendation

Overall safety Not recommended — antiandrogenic effects; feminisation of male fetus in animal studies

First trimester Contraindicated

Second/Third trimester Avoid; use only if no alternative and benefit clearly outweighs risk — specialist decision

Preferred alternatives For hypertension: Labetalol, Nifedipine, Methyldopa; For oedema: Furosemide (if essential)

Monitoring If inadvertently exposed: detailed fetal anomaly scan; monitor maternal electrolytes

Parameter Recommendation

Compatibility Generally compatible with breastfeeding

Drug levels in milk Low (active metabolite canrenone detected in low concentrations)

Preferred alternatives For hypertension: Amlodipine, Labetalol, Enalapril

Infant monitoring Hydration status, weight gain, urine output; watch for signs of electrolyte disturbance

Parameter Recommendation

Starting dose 12.5–25 mg once daily

Titration Slow; increase by 12.5–25 mg every 1–2 weeks

Maximum dose Generally limit to 50 mg/day unless specialist supervision

Extra risks Hyperkalaemia (reduced renal K⁺ excretion), hyponatraemia, postural hypotension, falls, acute kidney injury, gynaecomastia

Monitoring frequency Electrolytes and creatinine: baseline → 1 week → 1 month → every 1–3 months

Interacting Drug Effect Recommendation

ACE inhibitors (Enalapril, Ramipril, etc.) Additive hyperkalaemia; synergistic RAS blockade Can be used together with close K⁺ monitoring (standard in HF); avoid in CKD 4–5

ARBs (Losartan, Telmisartan, etc.) Additive hyperkalaemia Same as ACEi — monitor closely

Potassium supplements Severe hyperkalaemia risk Avoid combination unless documented hypokalaemia

Potassium-containing salt substitutes Hidden potassium load Counsel patients to avoid

Eplerenone Overlapping mechanism; additive toxicity Contraindicated — do not combine

Trimethoprim / Co-trimoxazole Trimethoprim blocks renal K⁺ excretion Avoid or monitor K⁺ very closely (especially in elderly, CKD)

NSAIDs (Ibuprofen, Diclofenac, etc.) Reduced diuretic efficacy; increased renal toxicity; hyperkalaemia Avoid long-term combination; if essential, monitor renal function and K⁺

Heparin / LMWH Aldosterone suppression; additive hyperkalaemia Monitor K⁺ especially in CKD/elderly

Mechanism: Spironolactone blocks aldosterone → reduced K⁺ excretion → synergistic hyperkalaemia with other K⁺-sparing mechanisms.

Interacting Drug Effect Recommendation

Digoxin Spironolactone increases digoxin half-life by ~20%; may interfere with digoxin assays Monitor digoxin levels; watch for toxicity (especially elderly)

Lithium Reduced lithium clearance → toxicity risk Monitor lithium levels closely; avoid if possible

Antidiabetic agents (Insulin, Sulfonylureas) Altered glycaemic control with volume status changes Monitor blood glucose during diuretic initiation/adjustment

Corticosteroids May antagonise diuretic and potassium-sparing effects Higher spironolactone doses may be needed; monitor BP and oedema

Carbenoxolone Antagonises spironolactone effect Avoid combination

Cholestyramine May reduce spironolactone absorption Separate administration by 2–4 hours

Aspirin (high-dose) May reduce diuretic efficacy Monitor clinical response

• Hyperkalaemia (dose-dependent; up to 10–15% in high-risk patients)

• Gynaecomastia and breast tenderness (dose and duration dependent; 10% at 50 mg/day)

• Menstrual irregularities (amenorrhoea, breakthrough bleeding)

• Decreased libido, erectile dysfunction

• Gastrointestinal upset (nausea, vomiting, diarrhoea, cramping)

• Fatigue, lethargy

• Dizziness, headache

• Skin rash

Adverse Effect Clinical Notes

Life-threatening hyperkalaemia Especially in CKD, elderly, diabetes, concurrent RAS blockers; may cause fatal arrhythmias; requires immediate discontinuation and treatment

Severe hyponatraemia Particularly in cirrhosis; may precipitate encephalopathy

Acute kidney injury Risk with volume depletion, NSAIDs, RAS blockers

Agranulocytosis Rare; discontinue if unexplained fever/infection

Stevens-Johnson syndrome / TEN Very rare; immediate discontinuation required

Hepatotoxicity Rare; monitor LFTs if symptoms suggest

Deep vein thrombosis Reported rarely; unclear mechanism

First 3 months Monthly electrolytes and renal function

Long-term (stable patients) Every 3–6 months; more frequent if CKD, diabetes, elderly, or on RAS blockers

Clinical monitoring Signs of hyperkalaemia (weakness, palpitations), gynaecomastia, volume status, BP

When to hold/discontinue:

• K⁺ ≥5.5 mEq/L — hold and recheck

• K⁺ ≥6.0 mEq/L — discontinue; treat hyperkalaemia

• Creatinine increase >30% from baseline — reassess

Brand Name Manufacturer Formulation

Aldactone Pfizer/RPG Tablets 25 mg, 50 mg, 100 mg

Spiromide Micro Labs Tablets

Spironol Intas Tablets

Lactone Sun Pharma Tablets

Silectone Alkem Tablets

Spiractin Cadila Tablets

Fixed-Dose Combinations (FDCs):

Brand Name Composition Manufacturer

NLEM 2022 Status: Spironolactone 25 mg tablet included — NPPA price ceiling applicable

Jan Aushadhi Availability: Yes — available at subsidised rates

1. Potassium is paramount: Hyperkalaemia is the most dangerous adverse effect — always check K⁺ before starting, after each dose change, and regularly during therapy. Risk is highest in CKD, diabetes, and elderly patients on ACEi/ARBs.

1. Heart failure mortality benefit: Spironolactone is one of the few drugs with proven mortality reduction in HFrEF — do not omit unless genuinely contraindicated. Start low (25 mg) and monitor.

1. Cirrhosis ratio rule: In ascites management, maintain spironolactone:furosemide ratio of approximately 100:40 to balance potassium and optimise diuresis.

1. Gynaecomastia management: If gynaecomastia is intolerable at ≥100 mg/day, consider dose reduction or switching to eplerenone (more selective, less antiandrogenic — but more expensive in India).

1. Contraception for antiandrogenic use: In women using spironolactone for acne, hirsutism, or PCOS — strict contraception is mandatory due to risk of feminising male fetus.

1. Delayed onset: Full antihypertensive effect may take 2–4 weeks; anti-androgenic effects (hirsutism, acne) may take 3–6 months — counsel patients appropriately.

potassium-sparing-diuretic; aldosterone-antagonist; heart-failure; resistant-hypertension; cirrhotic-ascites; hyperaldosteronism; hyperkalaemia-risk; renal-caution; NLEM-India; specialist-monitoring

RxIndia v1.1 — 30 May 2025

• CDSCO Product Database and approved prescribing information

• Indian Pharmacopoeia (IP)

• National List of Essential Medicines (NLEM) 2022

• API Textbook of Medicine

• ICMR Guidelines for Hypertension and CKD Management

• AIIMS Drug Formulary

• IAP Guidelines for Paediatric Diuretics

• Cardiological Society of India — Heart Failure Guidelines

• RALES Trial (off-label HF mortality evidence — NEJM 1999)

• Goodman & Gilman's The Pharmacological Basis of Therapeutics