Indapamide + Amlodipine

Oral
Essential hypertension

CrCl (mL/min)	Dosage
<30	Contraindicated.

Mild to moderate: Initiate at the lower end of the dosing range. Severe: Contraindicated.

Hypersensitivity to indapamide, amlodipine, or to other sulfonamide or dihydropyridine derivatives. Severe hypotension, shock (including cardiogenic shock), cardiac outflow obstruction, haemodynamically unstable heart failure after acute MI, hepatic encephalopathy, hypokalaemia. Severe renal (CrCl <30 mL/min) and hepatic impairment. Pregnancy and lactation.

Patient with heart failure, diabetes mellitus, hyperuricaemia, hypercalcaemia, risk factors for hypokalaemia (e.g. long QT interval, CAD, multiple medication use, malnourished patients, cirrhotic patients with oedema and ascites). Not recommended as initial therapy. Renal and mild to moderate hepatic impairment. Elderly.

Significant: Electrolyte disturbances (e.g. hypokalaemia, hyponatraemia, hypercalcaemia), hypotension, peripheral oedema; acute angle-closure glaucoma, choroidal effusions with visual field defect, transient myopia; photosensitivity reactions; hepatic encephalopathy, which may progress to hepatic coma (particularly in patients with liver impairment).
Cardiac disorders: Palpitations.
Eye disorders: Visual impairment including diplopia.
Gastrointestinal disorders: Abdominal pain, nausea, dyspepsia, diarrhoea, constipation.
General disorders and administration site conditions: Oedema, fatigue, asthenia.
Musculoskeletal and connective tissue disorders: Muscle spasms, ankle swelling.
Nervous system disorders: Dizziness, somnolence, headache.
Respiratory, thoracic and mediastinal disorders: Dyspnoea.
Skin and subcutaneous tissue disorders: Maculo-papular rash.
Vascular disorders: Flushing.
Potentially Fatal: Torsades de pointes (due to hypokalaemia).

This drug may cause dizziness, headache, or fatigue, if affected, do not drive or operate machinery. Avoid prolonged exposure to sunlight and UV lamps.

Monitor blood pressure, heart rate, serum electrolytes, uric acid, kidney or liver function, and glucose control (for diabetic patients). Assess for signs and symptoms of visual changes and peripheral oedema.

Symptoms: Indapamide: Water or electrolyte imbalances (e.g. hyponatraemia, hypokalaemia), nausea, vomiting, hypotension, vertigo, drowsiness, cramps, confusion, polyuria, oliguria, and anuria. Amlodipine: Excessive peripheral vasodilation, reflex tachycardia, marked and prolonged hypotension, and shock. Management: Perform gastric wash-out and/or give activated charcoal, then correct water or electrolyte balance. Initiate active CV support with frequent cardiac and respiratory function monitoring, elevation of extremities, and attention to circulating volume and urine output. Administration of a vasoconstrictor may help restore blood pressure and vascular tone. May give IV Ca gluconate to help reverse the effects of calcium channel blockade.

Indapamide: May increase serum lithium concentration. Increased risk of torsades de pointes with class Ia antiarrhythmic drugs (e.g. quinidine, disopyramide), class III antiarrhythmic drugs (e.g. amiodarone, bretylium, dofetilide, ibutilide, sotalol), phenothiazines (e.g. chlorpromazine, thioridazine), benzamides (e.g. amisulpride, sulpiride), butyrophenones (e.g. droperidol, haloperidol), pimozide, bepridil, cisapride, moxifloxacin, IV erythromycin, methadone, astemizole, and terfenadine. May decrease the antihypertensive effect with NSAIDs (including COX-2 inhibitors) and high-dose salicylic acid (≥3 g daily). Increased risk of acute renal failure or sudden hypotension with ACE inhibitors. Increased risk of hypokalaemia with IV amphotericin B, glucocorticoids, mineralocorticoids, tetracosactide, and stimulant laxatives. Cardiac glycoside toxicity may be enhanced due to the hypokalaemic and hypomagnesaemic effect of indapamide. Increased hypertensive effect with baclofen. May increase the risk of hypersensitivity reactions to allopurinol. Hypokalaemia or hyperkalaemia may occur (particularly in patients with renal failure or diabetes) with potassium-sparing diuretics (e.g. amiloride, spironolactone, triamterene). Increased risk of lactic acidosis with metformin. Increased risk of orthostatic hypotension and antihypertensive effect with imipramine-like antidepressants and neuroleptics.
Amlodipine: Increased risk of hyperkalaemia with dantrolene. Increased exposure with strong or moderate CYP3A4 inhibitors (e.g. protease inhibitors, azole antifungals, macrolides, verapamil, diltiazem). Decreased plasma concentration with CYP3A4 inducers (e.g. rifampicin). Additive blood pressure-lowering effects with other antihypertensives. May increase the exposure of simvastatin and mTOR inhibitors (e.g. sirolimus, everolimus, temsirolimus).

Amlodipine: Increased bioavailability with grapefruit or grapefruit juice. Decreased plasma concentration with St. John's wort.

May cause a false-negative aldosterone/renin ratio (ARR).
Indapamide: May interfere with parathyroid function tests and may reduce serum iodine (protein-bound) without signs of thyroid disturbance. May cause a positive reaction in doping tests.

Description:
Mechanism of Action: Indapamide, a sulfonamide with an indole ring, is a diuretic. It acts at the proximal segment of the distal tubule of the nephron and interferes with the transport of sodium ions across the renal tubular epithelium, resulting in enhanced sodium, chloride, and water excretion.
Amlodipine is a dihydropyridine calcium channel blocker. It acts directly on vascular smooth muscle to produce peripheral arterial vasodilation, thereby reducing peripheral vascular resistance and blood pressure.
Onset: Amlodipine: Antihypertensive effect: 24-48 hours.
Duration: Amlodipine: Antihypertensive effect: Approx 24 hours.
Pharmacokinetics:
Absorption: Indapamide: Rapidly and completely absorbed from the gastrointestinal tract. Bioavailability: 93%. Time to peak plasma concentration: 2 hours.
Amlodipine: Well absorbed. Bioavailability: Approx 64-90%. Time to peak plasma concentration: 6-12 hours.
Distribution: Crosses the placenta.
Indapamide: Volume of distribution: 25 L. Plasma protein binding: 71-79%.
Amlodipine: Enters breast milk. Volume of distribution: Approx 21 L/kg. Plasma protein binding: Approx 98%.
Metabolism: Extensively metabolised in the liver.
Excretion: Indapamide: Via urine (approx 70%; 7% as unchanged drug); faeces (23%). Elimination half-life: Biphasic: 14 and 25 hours.
Amlodipine: Via urine (60% as metabolites, 10% as unchanged drug). Terminal elimination half-life: Approx 35-50 hours.

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 3702, Indapamide. https://pubchem.ncbi.nlm.nih.gov/compound/Indapamide. Accessed Mar. 26, 2025.

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 2162, Amlodipine. https://pubchem.ncbi.nlm.nih.gov/compound/Amlodipine. Accessed Feb. 25, 2025.

Store below 30°C.

Calcium Antagonists / Diuretics

C08GA02 - amlodipine and diuretics ; Belongs to the class of calcium-channel blockers in combination with diuretics. Used in the treatment of cardiovascular diseases.

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