Adult: Perindopril arginine 5 mg, indapamide 1.25 mg and amlodipine 5 mg tab Perindopril arginine 5 mg, indapamide 1.25 mg and amlodipine 10 mg tab Perindopril arginine 10 mg, indapamide 2.5 mg and amlodipine 5 mg tab Perindopril arginine 10 mg, indapamide 2.5 mg and amlodipine 10 mg tab
As substitution therapy in patients who are controlled with perindopril/indapamide fixed-dose combination and amlodipine (given at the same dose level): 1 tab once daily, preferably in the morning before a meal. If dose adjustment is necessary, titration may be done with individual components. Dosage must be individualised. Available fixed-dose combinations may vary between countries (refer to local guidelines). Elderly: Dose adjustments may be required.
What are the brands available for Perindopril + Indapamide + Amlodipine in Malaysia?
Doses containing 10 mg perindopril arginine or 2.5 mg indapamide are contraindicated.
Hepatic Impairment
Mild to moderate: Amlodipine dose must be initiated at the lower end of the dosing range. Severe: Contraindicated.
Administration
Amlodipine + Indapamide + Perindopril arginine Should be taken on an empty stomach.
Contraindications
Hypersensitivity to perindopril, amlodipine, indapamide or other sulfonamide-derived drugs. Hereditary or idiopathic angioedema, history of angioedema associated with previous ACE inhibitor treatment; left ventricular outflow tract obstruction (e.g. high grade aortic stenosis), untreated decompensated heart failure, haemodynamically unstable heart failure following acute MI; hypokalaemia, severe hypotension, shock (including cardiogenic shock); extracorporeal treatments resulting in contact of blood with negatively charged surfaces; hepatic encephalopathy; significant bilateral renal artery stenosis or stenosis of the artery to a single functioning kidney. Moderate renal impairment (for doses containing 10 mg perindopril arginine or 2.5 mg indapamide); severe renal impairment, including patients undergoing dialysis. Severe hepatic impairment. Pregnancy (2nd or 3rd trimester) and lactation. Concomitant use with aliskiren-containing drugs in patients with diabetes mellitus or moderate to severe renal impairment (GFR <60 mL/min/1.73 m2). Concomitant use with or within 36 hours of switching to or from sacubitril/valsartan.
Special Precautions
Patient with history of angioedema unrelated to ACE inhibitor treatment; aortic or mitral stenosis, ischaemic heart disease, heart failure, hypertrophic cardiomyopathy with outflow tract obstruction; pre-existing sodium or volume depletion, risk factors for hyperkalaemia (e.g. worsening renal function, metabolic acidosis), cerebrovascular disease, collagen vascular disease, diabetes mellitus, primary aldosteronism, hyperuricaemia, ascites due to cirrhosis or refractory ascites; risk factors for acute angle-closure glaucoma (e.g. history of penicillin allergy). Patients undergoing major surgery, LDL apheresis with dextran sulfate, and desensitisation treatment with hymenoptera venom. Black race. Not suitable for use as initial therapy. Moderate renal impairment (for lower doses); mild to moderate hepatic impairment. Elderly. Not recommended during the 1st trimester of pregnancy.
Adverse Reactions
Significant: CNS effects (e.g. dizziness, lightheadedness, syncope), dry or non-productive cough, electrolyte disturbances (e.g. hyperkalaemia, hypercalcaemia, hypokalaemia, hypomagnesaemia, hyponatraemia, hypochloraemic alkalosis), symptomatic hypotension with or without syncope (usually during initial doses), renal function deterioration (e.g. increased serum creatinine, oliguria), hepatic encephalopathy (particularly in liver impairment with electrolyte imbalance); photosensitivity, ocular effects (e.g. choroidal effusion with visual field defect, transient myopia, acute angle-closure glaucoma). Rarely, neutropenia, agranulocytosis, thrombocytopenia, anaemia; angioedema of the face, lips, extremities, or intestines. Cardiac disorders: Palpitations. Ear and labyrinth disorders: Tinnitus, vertigo. Eye disorders: Visual impairment, diplopia, blurred vision. Gastrointestinal disorders: Nausea, vomiting, abdominal pain, constipation, diarrhoea, dyspepsia, change of bowel habit, dry mouth, dysgeusia. General disorders and administration site conditions: Asthenia, fatigue, oedema. Musculoskeletal and connective tissue disorders: Muscle spasms, ankle swelling. Nervous system disorders: Headache, somnolence, paraesthesia, hypoaesthesia. Respiratory, thoracic and mediastinal disorders: Dyspnoea. Skin and subcutaneous tissue disorders: Pruritus, rash, maculopapular rash. Vascular disorders: Flushing. Potentially Fatal: Anaphylactic/anaphylactoid reactions. Rarely, angioedema of the tongue, glottis or larynx; cholestatic jaundice that may progress to fulminant hepatic necrosis.
Patient Counseling Information
This drug may cause dizziness or lightheadedness, if affected, do not drive or operate machinery. Avoid prolonged exposure to sunlight and UV lamps.
Monitoring Parameters
Monitor blood pressure, heart rate, and serum electrolytes (particularly serum potassium monitoring within the 1st week); serum creatinine (after 2 weeks, then every 2 months in patients at risk for renal impairment), BUN; hepatic function at baseline then as clinically indicated; uric acid and blood glucose as necessary. Periodically monitor CBC with differential in patients with collagen vascular disease and/or renal impairment.
Overdosage
Symptoms: Perindopril/indapamide: Hypotension, dizziness, sleepiness, mental confusion, nausea, vomiting, cramps, oliguria which may lead to anuria, and water or salt disturbances (e.g. low sodium or potassium levels). Amlodipine: Excessive peripheral vasodilation, reflex tachycardia, and marked or prolonged systemic hypotension, including shock. Management: Symptomatic and supportive treatment. Consider administration of activated charcoal within 2 hours of ingestion or perform gastric lavage, then restore fluid and electrolyte balance until they return to normal levels. Provide active CV support, including frequent monitoring of cardiac and respiratory function, elevation of extremities, and attention to circulating fluid volume and urine output for clinically significant hypotension. If not contraindicated to its use, a vasoconstrictor may be considered for restoring vascular tone and blood pressure. May also give IV calcium gluconate to reverse calcium channel blockade effects.
Drug Interactions
Concomitant use with NSAIDs (including COX-2 inhibitors and high-dose aspirin) may result in worsening of renal function and reduced antihypertensive effect. Increased antihypertensive effect and risk of orthostatic hypotension with imipramine-like antidepressants (tricyclics) and neuroleptics. May cause additional blood pressure-lowering effect with other antihypertensive agents and baclofen. May increase serum lithium concentration and the risk of lithium toxicity.
Perindopril: May increase the risk of angioedema with racecadotril, mTOR inhibitors (e.g. everolimus, sirolimus), gliptins (e.g. linagliptin, sitagliptin), and estramustine. Increased risk of hyperkalaemia with potassium-sparing diuretics (e.g. spironolactone, amiloride), potassium supplements, potassium-containing salt substitutes, heparin, ciclosporin, and trimethoprim/sulfamethoxazole. Increased risk of hypotension, hyperkalaemia, and decreased renal function with ARBs. May increase blood glucose-lowering effect with antidiabetic agents (e.g. insulin, oral hypoglycaemic agents). May increase the risk of leucopenia with allopurinol, cytostatic or immunosuppressive agents, systemic corticosteroids, or procainamide. May further decrease blood pressure with glyceryl trinitrate, other nitrates, or other vasodilators. May enhance the hypotensive effects of certain anaesthetic drugs. May lead to volume depletion and increase the risk of hypotension with thiazide or loop diuretics. May diminish the antihypertensive effects with sympathomimetics. May cause nitritoid reactions with sodium aurothiomalate.
Indapamide: Increased risk of hypokalaemia with IV amphotericin B, glucocorticoids, systemic mineralocorticoids, tetracosactide, and stimulant laxatives. Increased risk of hypokalaemia and subsequently torsades de pointes with class Ia antiarrhythmic drugs (e.g. quinidine, disopyramide), class III antiarrhythmic drugs (e.g. amiodarone, sotalol), phenothiazines (e.g. chlorpromazine, levomepromazine, thioridazine), benzamides (e.g. amisulpride, sulpiride), butyrophenones (e.g. droperidol, haloperidol), pimozide, bepridil, cisapride, halofantrine, mizolastine, moxifloxacin, pentamidine, methadone, astemizole and terfenadine. Toxic effects of cardiac glycosides may be increased due to the hypokalaemic and hypomagnesaemic effects of indapamide. May increase the incidence of hypersensitivity reactions to allopurinol. May result in lactic acidosis with metformin. May increase the risk of acute renal insufficiency with high doses of iodinated contrast media.
Amlodipine: May increase the risk of hyperkalaemia with dantrolene. May decrease plasma concentration with CYP3A4 inducers (e.g. rifampicin). May increase exposure with moderate or strong CYP3A4 inhibitors (e.g. protease inhibitors, azole antifungals, erythromycin, clarithromycin, diltiazem, verapamil). May increase the serum concentrations of simvastatin, tacrolimus or ciclosporin. May increase exposure of mTOR inhibitors. Potentially Fatal: Perindopril: Increased risk of angioedema with sacubitril/valsartan. Concomitant use with aliskiren increases the risk of hyperkalaemia, worsening of renal function and CV morbidity, particularly in patients with diabetes or renal impairment. May increase the risk of severe anaphylactoid reactions during LDL apheresis with dextran sulfate.
Food Interaction
Perindopril: Food reduces the conversion into perindoprilat which may lower its concentrations.
Indapamide: Increased orthostatic hypotensive effect with alcohol.
Amlodipine: May increase bioavailability with grapefruit or grapefruit juice. May decrease plasma concentration with St. John's wort.
Lab Interference
May result in 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.
Action
Description: Mechanism of Action: Perindopril, indapamide and amlodipine combination work with complementary mechanisms to produce additive antihypertensive effects.
Perindopril, a prodrug of perindoprilat, is an ACE inhibitor. It prevents the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor. This action leads to lower angiotensin II levels, thereby increasing plasma renin activity and reducing aldosterone secretion.
Indapamide, a sulfonamide derivative thiazide-related diuretic, acts at the proximal segment of the distal tubule of the nephron. It interferes with the transport of sodium ions across the renal tubular epithelium, thereby enhancing the excretion of sodium, chloride, and water.
Amlodipine, a dihydropyridine calcium channel blocker, inhibits the transmembrane influx of calcium ions into the cardiac and vascular smooth muscle during depolarisation, thus resulting in coronary vascular smooth muscle relaxation and vasodilation. It also directly acts on vascular smooth muscles, causing peripheral arterial vasodilation, which decreases peripheral vascular resistance and blood pressure. Onset: Perindopril: 1-2 hours.
Amlodipine: Antihypertensive effect: 24-48 hours. Duration: Amlodipine: Antihypertensive effect: Approx 24 hours. Pharmacokinetics: Absorption: Perindopril: Rapidly absorbed. Food reduces the conversion into perindoprilat which may lower its concentrations. Bioavailability: Approx 75% (perindopril); approx 25% (perindoprilat); approx 16% (perindoprilat given with food). Time to peak plasma concentration: Approx 1 hour (perindopril); 3-7 hours (perindoprilat).
Indapamide: Rapidly and completely absorbed from the gastrointestinal tract. Bioavailability: 93%. Time to peak plasma concentration: 2 hours.
Amlodipine: Well absorbed. Bioavailability: 64-90%. Time to peak plasma concentration: 6-12 hours. Distribution: Perindopril: Enters breast milk (perindopril and perindoprilat). Volume of distribution: Approx 0.2 L/kg (unbound perindoprilat). Plasma protein binding: Approx 60% (perindopril); 10-20% (perindoprilat).
Indapamide: Volume of distribution: 25 L. Plasma protein binding: 71-79%.
Amlodipine: Crosses the placenta and enters breast milk. Volume of distribution: 21 L/kg. Plasma protein binding: Approx 93%. Metabolism: Perindopril: Extensively metabolised in the liver via hydrolysis into perindoprilat (active metabolite) and other inactive metabolites, including glucuronides.
Indapamide: Extensively metabolised in the liver.
Amlodipine: Extensively metabolised in the liver into inactive metabolites. Excretion: Perindopril: Via urine (75%; 4-12% as unchanged drug). Elimination half-life: 1.5-3 hours (perindopril); 25-30 hours or longer (perindoprilat).
Indapamide: Via urine (approx 70%; 7% as unchanged drug); faeces (23%). Elimination half-life: Biphasic: 14 and 25 hours.
Amlodipine: Via urine (10% as unchanged drug, 60% as metabolites). Terminal elimination half-life: 30-52 hours.
Chemical Structure
Perindopril Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 107807, Perindopril. https://pubchem.ncbi.nlm.nih.gov/compound/Perindopril. Accessed Apr. 29, 2025.
Indapamide 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.
Amlodipine 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.
C09BX01 - perindopril, amlodipine and indapamide ; Belongs to the class of ACE inhibitors and other combinations. Used in the treatment of cardiovascular disease.
References
Amlodipine. UpToDate Lexidrug, Lexi-Drugs Multinational Online. Waltham, MA. UpToDate, Inc. https://online.lexi.com. Accessed 07/07/2025.Brayfield A, Cadart C (eds). Amlodipine. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 07/07/2025.Brayfield A, Cadart C (eds). Indapamide. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 07/07/2025.Brayfield A, Cadart C (eds). Perindopril. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 07/07/2025.Indapamide. UpToDate Lexidrug, Lexi-Drugs Multinational Online. Waltham, MA. UpToDate, Inc. https://online.lexi.com. Accessed 07/07/2025.Perindopril, Indapamide, and Amlodipine. UpToDate Lexidrug, Lexi-Drugs Multinational Online. Waltham, MA. UpToDate, Inc. https://online.lexi.com. Accessed 07/07/2025.Perindopril. UpToDate Lexidrug, Lexi-Drugs Multinational Online. Waltham, MA. UpToDate, Inc. https://online.lexi.com. Accessed 07/07/2025.Triplixam 5 mg/1.25 mg/5 mg, 5 mg/1.25 mg/10 mg, 10 mg/2.5 mg/5 mg, 10 mg/2.5 mg/10 mg Film-coated Tablets (Servier Hong Kong Ltd). MIMS Hong Kong. http://www.mims.com/hongkong. Accessed 07/07/2025.Triplixam 5 mg/1.25 mg/5 mg, 5 mg/1.25 mg/10 mg, 10 mg/2.5 mg/5 mg, and 10 mg/2.5 mg/10 mg Film-coated Tablets (Servier Malaysia Sdn Bhd). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 16/07/2025.Triplixam 5 mg/1.25 mg/5 mg, 5 mg/1.25 mg/10 mg, and 10 mg/2.5 mg/10 mg Film-coated Tablets (Servier Philippines, Inc). MIMS Philippines. http://www.mims.com/philippines. Accessed 07/07/2025.
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