Products
Indapamide is commercially available as tablets and capsules alone in sustained-release formulations (Fludex SR, generic) and in combination with the ACE inhibitor perindopril (Coversum N Combi, generic). A fixed combination of perindopril, indapamide, and amlodipine is also available (Coveram plus). Indapamide was developed in the 1970s and has been approved in many countries since 1993.
Structure and properties
Indapamide (C16H16ClN3O3S, Mr = 365.83 g/mol) is a chlorosulfonamide and a methylindoline derivative pharmacologically related to the thiazide diuretics. Structurally, it is not a thiazide, but similarities exist. Indapamide is racemic and exists as a white to near-white powder that is virtually insoluble in water.
Effects
Indapamide (ATC C03BA11) has diuretic, natriuretic, kaliuretic, and antihypertensive properties. The effects are due to inhibition of sodium reabsorption in the distal renal tubule by blockade of the NaCl cotransporter. The potassium-uretic effect occurs mainly at high doses. This also increases the risk of hypokalemia. Indapamide is administered as sustained-release dosage forms and at low doses to keep the risk of adverse effects low. It has further shown pleiotropic effects in studies that are independent of diuretic effects.
Indications
Indapamide approved in combination with perindopril for the treatment of essential hypertension (high blood pressure) and stable coronary artery disease. As a monopreparation, it is approved for the treatment of hypertension.
Dosage
The usual adult dose is 0.625 mg or 1.25 mg (in combination with perindopril) or 1.5 mg (sustained-release) once daily in the morning.
Contraindications
- Hypersensitivity, hypersensitivity to sulfonamides.
- Severe renal insufficiency
- Severe hepatic insufficiency
- Hepatic encephalopathy
- Hypokalemia
- Following a recent cerebrovascular incident.
- Pregnancy, lactation
- Children
For complete precautions and information on possible drug-drug interactions, see the drug label.
Adverse effects
The most common possible adverse effects include headache, dizziness, weakness, sensory disturbances such as formication, digestive symptoms such as nausea, constipation, dry mouth, and vomiting, and hypokalemia due to increased excretion of potassium. In combination with the ACE inhibitor perindopril, the risk for hypokalemia could theoretically decrease because perindopril is potassium-retentive. Occasionally, indapamide may cause hyponatremia due to increased sodium excretion, resulting in hypovolemia, dehydration, and increased hypotension with low blood pressure. Urea and glucose levels may be increased.
