Side Effects of Indapamide
Indapamide's most common side effects include electrolyte disturbances (particularly hypokalemia), metabolic changes, and mild gastrointestinal symptoms. 1
Common Side Effects
- Electrolyte disturbances: Hypokalemia is the most significant concern, with studies showing 47% of patients on indapamide 2.5 mg having at least one potassium value below 3.5 mEq/L 1
- Metabolic effects: Hyperuricemia (average increase of 0.69-1.0 mg/dL), glucose intolerance, and acid-base disturbances 1, 2
- Gastrointestinal symptoms: Nausea, constipation, gastric irritation, and abdominal pain 1
- Central nervous system: Headache, dizziness, and nervousness 1
- Other common effects: Fatigue, asthenia, and peripheral edema 1
Electrolyte Abnormalities
- Potassium: Hypokalemia risk increases with higher doses, brisk diuresis, and concomitant use of corticosteroids 1
- Sodium: Hyponatremia may occur, particularly in edematous patients 1
- Magnesium: Increased urinary excretion may lead to hypomagnesemia 1
- Calcium: Unlike other diuretics, indapamide causes only slight increases in serum calcium after prolonged treatment 1
Cardiovascular Effects
- Blood pressure: Orthostatic hypotension may occur, particularly in elderly patients or with volume depletion 2
- Cardiac effects: Indapamide has fewer negative effects on cardiac function compared to some other diuretics 3
Metabolic and Endocrine Effects
- Uric acid: Serum concentrations typically increase by 0.69-1.0 mg/dL, potentially precipitating gout in susceptible individuals 1
- Glucose metabolism: May cause glucose intolerance and alter insulin requirements in diabetic patients 1
- Lipid profile: Unlike some diuretics, indapamide has minimal adverse effects on lipid metabolism 3
Renal Effects
- Renal function: Should be used with caution in severe renal disease as reduced plasma volume may exacerbate azotemia 1
- Urinary calcium: Indapamide reduces urinary calcium excretion by 20-50% depending on the patient population 4
Hepatic Effects
- Liver function: Should be used cautiously in patients with impaired hepatic function as minor fluid/electrolyte imbalances may precipitate hepatic coma 1
- Rare reactions: Jaundice (intrahepatic cholestatic), hepatitis, and abnormal liver function tests have been reported 1
Dermatologic and Hypersensitivity Reactions
- Skin reactions: Rash, hives, pruritus, and photosensitivity 1
- Severe reactions: Erythema multiforme, Stevens-Johnson Syndrome, and vasculitis have been reported but are rare 1
Hematologic Effects
- Blood disorders: Rare reports of agranulocytosis, leukopenia, thrombocytopenia, and aplastic anemia 1
Dosage Considerations
- Initial dosing: The recommended initial dose is 2.5 mg once daily, taken in the morning 2
- Maximum dose: The maximum recommended daily dose is 2.5 mg 2
- Monitoring: Blood pressure, renal function, and electrolytes should be checked 1-2 weeks after each dose increment, at 3 months, and subsequently at 6-month intervals 2
Special Populations
- Renal impairment: Monitoring of renal function is essential; withhold or discontinue if progressive renal impairment is observed 1
- Hepatic impairment: Use with caution due to risk of precipitating hepatic coma 1
- Elderly: May be more sensitive to the hypotensive and electrolyte effects 2
Contraindications and Precautions
- Severe renal disease: Use with caution due to risk of azotemia 1
- Impaired hepatic function: Use with caution due to risk of precipitating hepatic coma 1
- Systemic lupus erythematosus: May exacerbate or activate the condition 1
- Acute angle-closure glaucoma: Sulfonamide-derivative drugs like indapamide can cause idiosyncratic reactions resulting in acute angle-closure glaucoma 1
Drug Interactions
- Other antihypertensives: May potentiate the action of other antihypertensive drugs 1
- Lithium: May increase risk of lithium toxicity 1
- NSAIDs: Should be avoided as they may reduce the antihypertensive effect and increase risk of renal impairment 2
- Potassium-sparing diuretics: Should be avoided during initiation of therapy 2