Indapamide

Cardiovascular

Indapamide has been associated with prolongation of the QT interval and Brugada syndrome in the setting of severe hypokalemia and hyponatremia [ ].

• A 64-year-old man developed generalized weakness and dizziness. He was taking indapamide 2.5 mg/day for hypertension. Electrocardiography showed coved ST segment elevation in V2 with deep T-wave inversion (type 1 Brugada pattern) and a prolonged QT interval of 508 ms. His serum potassium concentration was 1.7 mmol/l and serum sodium 111 mmol/l. He had a sudden cardiac arrest with a polymorphous ventricular tachycardia, which was successfully defibrillated. His QT _c interval gradually normalized as his serum potassium returned to normal; however, his Brugada pattern did not correct until his serum sodium had normalized some 48 hours later.

The exact mechanism by which the indapamide-related electrolyte disturbances resulted in Brugada syndrome in this case was unclear. Indapamide, and for that matter any diuretic that produces significant hypokalemia and hyponatremia, should be used with caution in patients who are genetically predisposed to or at risk of developing acquired long QT or Brugada syndromes.

Indapamide has been associated with QT interval prolongation and torsade de pointes independent of electrolyte changes [ ].

• A 42-year-old woman with systemic lupus erythematosus and hypertension developed palpitation and near syncope. Her medications included prednisolone 5 mg/day and indapamide 2.5 mg/day. A baseline electrocardiogram showed sinus rhythm, several episodes of non-sustained ventricular tachycardia, and a QT _c interval of 510 ms. Serum potassium, magnesium, and free calcium concentrations were all normal. Despite withdrawal of indapamide and prednisolone, torsade de pointes occurred and degenerated into ventricular fibrillation. Over the next two days the QT _c interval gradually shortened to 430 ms. Coronary angiography did not show any significant stenotic lesions.

Several non-antidysrhythmic drugs, including diuretics, prolong cardiac repolarization, predisposing to torsade de pointes. Diuretic-induced hypokalemia can exacerbate this effect. However, indapamide blocks the slow component of the delayed inward rectifier potassium current, leading to excessive lengthening of cardiac repolarization and thereby a predisposition to torsade de pointes. Indapamide should therefore be used with caution in patients who are at risk of torsade de pointes, especially when the patient is also taking drugs that block the rapid component of the delayed inward rectifier potassium current. Such drugs include class III antidysrhythmic drugs, macrolide antibiotics, antipsychotic drugs, and antihistamines.

Sensory systems

Transient myopia associated with diffuse choroidal thickening has been described in a 38-year-old white man who had taken indapamide for hypertension; it resolved after withdrawal [ ].