Spironolactone


Generic Medicine Info
Indications and Dosage
Oral
Malignant ascites
Adult: Initially, 100-200 mg daily, may be gradually increased up to 400 mg daily for severe cases. Maintenance dose must be adjusted according to individual response.
Child: Initially, 1-3 mg/kg daily in divided doses, may be adjusted according to response and tolerance.
Elderly: Initiate with the lowest dose and titrate upwards if needed.

Oral
Oedema
Adult: Initially, 100 mg daily, may be adjusted up to 400 mg daily according to response.

Oral
Congestive heart failure with oedema
Adult: For the management of oedema: Initially, 100 mg daily or 25-200 mg daily as a single dose or in divided doses. Maintenance dose must be adjusted according to individual response.
Child: Initially, 1-3 mg/kg daily in divided doses, may be adjusted according to response and tolerance.
Elderly: Initiate with the lowest dose and titrate upwards if needed.

Oral
Nephrotic syndrome
Adult: If glucocorticoids are insufficiently effective: Usual dose: 100-200 mg daily.
Child: Initially, 1-3 mg/kg daily in divided doses, may be adjusted according to response and tolerance.
Elderly: Initiate with the lowest dose and titrate upwards if needed.

Oral
Diagnosis of primary hyperaldosteronism
Adult: Long test: 400 mg daily for 3-4 weeks. Short test: 400 mg daily for 4 days.
Child: Initially, 1-3 mg/kg daily in divided doses, may be adjusted according to response and tolerance.
Elderly: Initiate with the lowest dose and titrate upwards if needed.

Oral
Hypertension
Adult: Adjunct in patients who are not adequately controlled on other agents: As tab: Initially, 25-100 mg daily as a single dose or in divided doses. As susp: Initially, 20-75 mg daily a single dose or in divided doses. Dosage may be titrated at 2-week intervals, if needed, according to response and tolerability.

Oral
Preoperative management of hyperaldosteronism
Adult: 100-400 mg daily. As long-term maintenance therapy in patients who are considered unsuitable for surgery: Use the lowest effective dose.
Child: Initially, 1-3 mg/kg daily in divided doses, may be adjusted according to response and tolerance.
Elderly: Initiate with the lowest dose and titrate upwards if needed.

Oral
Hepatic cirrhosis with ascites and oedema
Adult: Initiate treatment in the hospital and slowly titrate the dose. If urinary Na/K ratio is >1: Initially, 100 mg daily. If urinary Na/K ratio is <1: Initially, 200-400 mg daily. Maintenance dose must be adjusted according to individual response.
Child: Initially, 1-3 mg/kg daily in divided doses, may be adjusted according to response and tolerance.
Elderly: Initiate with the lowest dose and titrate upwards if needed.

Oral
Heart failure
Adult: In conjunction with standard therapy for the treatment of New York Heart Association (NYHA) Class III-IV cases: Patients with serum K ≤5 mEq/L and eGFR >50 mL/min/1.73 m2: As tab: Initially, 25 mg once daily, if tolerated, may be increased to 50 mg once daily as clinically indicated. As susp: Initially, 20 mg once daily, if tolerated, may be increased to 37.5 mg once daily as clinically indicated. Patients who develop hyperkalaemia on initial dose: As tab: May reduce dose to 25 mg every other day. As susp: May reduce dose to 20 mg every other day.
Child: As tab: Initially, 1-3 mg/kg daily in divided doses, may be adjusted according to response and tolerance.
Elderly: Initiate with the lowest dose and titrate upwards if needed.
Renal Impairment
Heart failure:
eGFR 30-50 mL/min/1.73 m2: As tab: Initially, 25 mg every other day. As susp: Initially, 10 mg once daily.
Administration
Should be taken with food.
Contraindications
Hyperkalaemia, Addison’s disease, anuria, acute renal insufficiency, diabetic nephropathy. Severe renal impairment. Children with moderate to severe renal impairment. Lactation. Concomitant use with eplerenone or other K-sparing diuretics, and K supplements (except in cases of initial K depletion).
Special Precautions
Patient with diabetes mellitus, porphyria, menstrual abnormalities or breast enlargement; cirrhosis, predisposition to respiratory or metabolic acidosis, salt-depletion. Patient with heart failure: eGFR must be >30 mL/min/1.73 m2 or creatinine must be ≤2.5 mg/dL (men) or ≤2 mg/dL (women) with no recent worsening, and K <5 mEq/L with no history of severe hyperkalaemia. Discontinue use prior to adrenal vein catheterisation. Susp is not therapeutically equivalent to tab; patient requiring >100 mg/dose should use tab. Avoid unnecessary use. Renal and hepatic impairment. Children and elderly. Pregnancy.
Adverse Reactions
Significant: Fluid-electrolyte imbalance (e.g. hypomagnesaemia, hyponatraemia, hypocalcaemia, hyperglycaemia), hyperchloraemic metabolic acidosis (reversible), asymptomatic hyperuricaemia, gout, gynaecomastia (reversible), symptomatic dehydration, hypotension, and worsened renal function; increased BUN (reversible).
Blood and lymphatic system disorders: Rarely, agranulocytosis, leucopenia, thrombocytopenia.
Gastrointestinal disorders: Nausea, vomiting, diarrhoea, gastritis, gastrointestinal ulcer or haemorrhage.
General disorders and administration site conditions: Malaise, ataxia, fever.
Hepatobiliary disorders: Hepatotoxicity.
Immune system disorders: Rarely, hypersensitivity.
Metabolism and nutrition disorders: Hypovolaemia.
Musculoskeletal and connective tissue disorders: Muscle spasms.
Nervous system disorders: Dizziness, headache, drowsiness.
Psychiatric disorders: Confusional state.
Renal and urinary disorders: Acute kidney injury.
Reproductive system and breast disorders: Breast pain, benign breast neoplasm (male), decreased libido, irregular menses, erectile dysfunction, postmenopausal bleeding.
Skin and subcutaneous tissue disorders: Pruritus, rash, urticaria, toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), drug rash with eosinophilia and systemic symptoms (DRESS), alopecia, hypertrichosis.
Potentially Fatal: Hyperkalaemia.
Patient Counseling Information
This drug may cause dizziness, drowsiness or somnolence, if affected, do not drive or operate machinery. Do not switch between dosage forms unless instructed by your doctor.
MonitoringParameters
Monitor blood pressure, uric acid, blood glucose, renal function, volume status, and BUN periodically; serum electrolytes, including K (within 1 week of treatment initiation or dose titration, and regularly thereafter) and Na. Closely monitor serum K and renal function 3 days after initiating therapy, at 1 week after initiation, at least monthly for the 1st 3 months of treatment, and every 3 months thereafter for patient with heart failure.
Overdosage
Symptoms: Drowsiness, dizziness, mental confusion, nausea, vomiting, diarrhoea, maculopapular or erythematous rash. Rarely, hyponatraemia, hyperkalaemia manifested as paraesthesia, flaccid paralysis, muscle weakness or spasm; hepatic coma. Management: Supportive treatment. Perform gastric lavage or induce vomiting. Maintain hydration, electrolyte balance and vital functions. For hyperkalaemia, may decrease K intake, administer K-excreting diuretics, IV glucose with regular insulin or oral ion-exchange resins.
Drug Interactions
Reduced renal clearance of lithium thereby increased risk of lithium toxicity. Diuretic, natriuretic, and antihypertensive effects may be reduced by NSAIDs (e.g. aspirin, indometacin, mefenamic acid). May increase the serum levels of digoxin. May cause hyperkalaemic metabolic acidosis with colestyramine. May potentiate the hypotensive effects of antihypertensives. Effectiveness may be decreased by carbenoxolone. May reduce the vascular response to norepinephrine. May increase the risk of hyponatraemia with chlorpropamide.
Potentially Fatal: Increased risk of severe hyperkalemia with eplerenone and other K-sparing diuretics (e.g. amiloride, triamterene), K supplements, ACE inhibitors, angiotensin receptor blockers, NSAIDs, heparin, LMWH, ciclosporin, and co-trimoxazole.
Food Interaction
Increased bioavailability with food. Orthostatic hypotension may be potentiated by alcohol.
Lab Interference
May interfere with the radioimmunoassay of digoxin; may result to false negative aldosterone/renin ratio (ARR). May interfere with the estimation of compounds with similar fluorescence characteristics in fluorimetric assays. May enhance the metabolism of antipyrine used in LFTs.
Action
Description: Spironolactone is a steroid with a structure that resembles aldosterone. It competitively inhibits aldosterone receptors in the distal convoluted renal tubules, thereby increasing the excretion of NaCl and water while conserving K and hydrogen ions.
Duration: 2-3 days (tab).
Pharmacokinetics:
Absorption: Well absorbed from the gastrointestinal tract. Bioavailability: Approx 90%, increased with high fat or calorie meal. Time to peak plasma concentration: Tab: 2.6-4.3 hours (mainly as active metabolites); Susp: 0.5-1.5 hours (spironolactone); 2.5-5 hours (canrenone).
Distribution: Crosses the placenta and enters breastmilk (as canrenone). Plasma protein binding: >90%.
Metabolism: Rapidly and extensively metabolised in the liver to several active metabolites: canrenone, 7-α-spironolactone, and 6-β-hydroxy-7-α).
Excretion: Via urine (mainly as metabolites); faeces (secondary). Elimination half-life: 1.4 hours (tab); 1-2 hours (susp).
Chemical Structure

Chemical Structure Image
Spironolactone

Source: National Center for Biotechnology Information. PubChem Database. Spironolactone, CID=5833, https://pubchem.ncbi.nlm.nih.gov/compound/Spironolactone (accessed on Jan. 23, 2020)

Storage
Tab/susp: Store between 20-25°C. Protect from light and moisture.
MIMS Class
ATC Classification
C03DA01 - spironolactone ; Belongs to the class of aldosterone antagonists. Used as potassium-sparing diuretics.
References
Anon. Spironolactone. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 08/05/2020.

Buckingham R (ed). Spironolactone. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 08/05/2020.

Carospir Suspension (Atlantic Biologicals Corp.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 08/05/2020.

Joint Formulary Committee. Spironolactone. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 08/05/2020.

Spironolactone 25 mg Tablets (Bristol Laboratories). MHRA. https://products.mhra.gov.uk/. Accessed 08/05/2020.

Spironolactone Tablet (Amneal Pharmaceuticals LLC). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 08/05/2020.

Spironolactone Tablet, Film Coated (McKesson Corporation dba SKY Packaging). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 08/05/2020.

Disclaimer: This information is independently developed by MIMS based on Spironolactone from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2021 MIMS. All rights reserved. Powered by MIMS.com
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