Table 3 Withdrawal criteria

Blood pressure

Hypotension

Withdraw trial medication if systolic blood pressure <100 mmHg or postural drop of systolic blood pressure >20 mmHg.

Metabolic

Hyperkalaemia

Withdraw trial medication if serum potassium ≥ 6 mEq/l on repeat sampling.

Hyponatraemia

Withdraw trial medication if serum sodium <130 mEq/l on two occasions.

Renal

Renal dysfunction

Withdraw trial medication if serum creatinine increment ≥30% or eGFR reduction ≥25% from baseline.

Endocrine

Men: gynaecomastia, impotence, diminished libido

Withdraw trial medication if participant is intolerant of the side effect or effects.

Women: hirsutism, oligomenorrhoea, amenorrhoea, menorrhagia, breast tenderness

Nervous system

Headache

Withdraw trial medication if symptom persists for >1 week.

Confusion, ataxia, drowsiness

Check postural blood pressure and serum sodium level. If postural blood pressure and serum sodium levels are within normal levels, but symptoms persist for >1 week, withdraw trial medication.

Lethargy

Withdraw trial medication if symptom persists for >1 week.

Dermatological

Rash

Withdraw trial medication.

Lichen planus, lupus-like syndrome

Withdraw trial medication.

Hypersensitivity

Anaphylaxis, contact dermatitis, eosinophilia

Withdraw trial medication immediately.

Gastrointestinal

General abdominal discomfort

Withdraw trial medication if persistent discomfort for >1 week.

Diarrhoea or vomiting

Withdraw trial medication if persistent diarrhoea or vomiting for >3 days.

Gastric or duodenal ulcer or bleeding

Withdraw trial medication.

Haematological

Agranulocytosis

Withdraw trial medication.

Hepatic

Hepatotoxicity (alanine transferase > 123 U/l or bilirubin > 44 μmol/l)

Withdraw trial medication.

Oncological

Animal studies suggested association between spironolactone with benign adenoma of the thyroid and testes, malignant breast tumours, hepatocellular carcinoma and leukemia

Withdraw trial medication.