Amlodipine + Perindopril + Indapamide

Amlodipine + Perindopril + Indapamide is used for: Substitution therapy for treatment of essential HTN, in patients already controlled w/ perindopril/indapamide fixed-dose combination & amlodipine, taken at the same dose level

Oral Tablet 1 tablet daily as single dose. NOTE: The fixed dose combination is not suitable for initial therapy. If a change of the posology is required, titration should be done with the individual components

The safety and efficacy in children and adolescents have not been established. No data are available

Renal impairment: In severe renal impairment (creatinine clearance below 30 mL/min), treatment is contraindicated. In patients with moderate renal impairment (creatinine clearance 30-60 mL/min), the doses 10mg/2.5mg /5mg and 10mg/2.5mg/10mg are contraindicated. It is recommended to start treatment with the adequate dosage of the free combination

Administer preferably in the morning and before a meal. Food intake may reduce hepatic biotransformation of Perindopril to Perindoprilat.

Hypersensitivity to perindopril, indapamide, amlodipine, other sulfonamides, dihydropyridine derivatives, any other ACE inhibitor. Patients w/ untreated decompensated heart failure; dialysis patients; history of angioedema (Quincke's oedema) associated w/ previous ACE inhibitor therapy, hereditary/idiopathic angioedema; hepatic encephalopathy; hypokalaemia; severe hypotension; cardiogenic shock; high grade aortic stenosis, haemodynamically unstable heart failure after acute MI. Significant bilateral renal artery stenosis or artery stenosis to a single functioning kidney. Concomitant use w/ sacubitril/valsartan; extracorporeal treatments. Concomitant use w/ aliskiren-containing products in patients w/ DM or renal impairment (GFR <60 mL/min/1.73 m2). Severe renal impairment (CrCl <30 mL/min). Hepatic impairment. Use of 10 mg/2.5 mg/5 mg & 10 mg/2.5 mg/10 mg in moderate renal impairment (CrCl <60 mL/min) 2nd & 3rd trimester pregnancy. Lactation

Hypersensitivity/angioedema; anaphylactoid reactions during desensitization & LDL apheresis. Discontinue use if photosensitivity, hepatic encephalopathy, hypertensive patients w/o preexisting apparent renal lesions occur. Not suitable for initial therapy. Not recommended in dual blockade of the renin-angiotensin-aldosterone system; primary aldosteronism, bilateral renal artery stenosis or stenosis of the artery to a solitary kidney. Not to be used concomitantly in patients w/ diabetic nephropathy. Severe heart failure (NYHA class III & IV), severe cardiac insufficiency (Grade IV); left ventricle outflow tract obstruction. Collagen vascular disease, immunosuppressant therapy; CHF or cirrhosis w/ oedema & ascites; ischaemic heart disease or cerebral circulatory insufficiency; aortic or mitral valve stenosis/hypertrophic cardiomyopathy; DM. Renovascular HTN; undiagnosed hyperparathyroidism, hyperuricaemic. Dry cough. Black patients. Haemodialysis patients. Regular monitoring of plasma electrolytes & K levels. Discontinue 1 day prior to surgery. Not to be initiated until 36 hr after sacubitril/valsartan last dose. Not recommended in combination w/ lithium, K-sparing diuretics, K supplements or K-containing salt substitutes. Concomitant use w/ allopurinol or procainamide; mTOR inhibitors e.g., sirolimus, everolimus, temsirolimus; other NEP inhibitors e.g., racecadotril. May affect ability to drive & use machines. Mild to moderate hepatic impairment. Not recommended during 1st trimester of pregnancy. Lactation. Childn & adolescents. Elderly Pregnancy & Lactation Given the effects of the individual components in this combination product on pregnancy and lactation, this drug is not recommended during the first trimester of pregnancy. This is contraindicated during the second and third trimesters of pregnancy. This drug is contraindicated during lactation. A decision should therefore be made whether to discontinue nursing or to discontinue this taking into account the importance of this therapy for the mother

Increased risk of hyperkalaemia w/ aliskerin, K-salts, K-sparing diuretics, ACE inhibitors, AIIA receptors antagonists, NSAIDs, heparins, immunosuppressants (e.g., ciclosporine or tacrolimus), trimethoprim, co-trimoxazole. Increased risk of severe anaphylactoid reactions w/ extracorporeal treatments. Increased risk of angioedema w/ sacubitril/valsartan, racecadotril, mTOR inhibitors eg, sirolimus, everolimus, temsirolimus; gliptines eg, linagliptine, saxagliptine, sitagliptin, vildagliptin. Increased antihypertensive effect & risk of orthostatic hypotension w/ imipramine-like antidepressants e.g., TCAs, neuroleptics. Additive effect w/ IV amphotericin B, gluco- & mineralocorticoids (systemic route), tetracosactide, stimulant laxatives. Additive BP lowering effect w/ other antihypertensives. Reduced antihypertensive effect w/ corticosteroids, tetracosactide; sympathomimetics. Reversible increase in serum conc & toxicity of lithium. Increased antihypertensive effects w/ baclofen. Attenuated antihypertensive effects w/ NSAIDs e.g., acetylsalicylic acid, COX-2 inhibitors & non-selective NSAIDs. Increased risk of hyperkalaemia, worsened renal function & CV morbidity & mortality w/ aliskerin. Higher frequency of hypotension, syncope, hyperkalaemia & worsened renal function w/ angiotensin-receptor blocker. Increased risk of angioneurotic oedema w/ estramustine. Additive hyperkalaemic effect w/ K-sparing drugs e.g., triamterene, amiloride; K-salts. Increased blood-glucose lowering effects w/ antidiabetics e.g., insulin, oral hypoglycemics. Reduced hypotensive effects w/ non-K-sparing diuretics. Reduced BP w/ nitroglycerin & other nitrates or other vasodilators. Increased risk of leucopenia w/ allopurinol, cytostatic or immunosuppressive agents, systemic corticosteroids or procainamide. Lethal ventricular fibrillation & CV collapse w/ dantrolene (infusion). Increased bioavailability w/ grapefruit or grapefruit juice. Lowered plasma conc by CYP3A4 inducers e.g., rifampicin, Hypericum perforatum. Increased amlodipine exposure w/ strong or moderate CYP3A4 inhibitors e.g., PIs, azole antifungals, macrolides (e.g., erythromycin or clarithromycin), verapamil, diltiazem. Risk of hyperkalaemia w/ K-sparing diuretics e.g., eplerenone, spironolactone. Risk of hypokalaemia w/ Torsade de pointes-inducing drugs. Increased incidence of hypersensitivity reactions to allopurinol. Enhanced hypotensive effects w/ anaesthetics. Volume depletion & risk of hypotension w/ diuretics e.g., thiazide or loop diuretics. Nitritoid reactions w/ injectable gold (Na aurothiomalate). Increased risk of acute renal insufficiency w/ iodinated contrast media (high doses)

Side effects of Amlodipine + Perindopril + Indapamide : The most commonly reported adverse reactions with perindopril, indapamide and amlodipine given separately are: dizziness, headache, paraesthesia, somnolence, dysgeusia, visual impairment, diplopia, tinnitus, vertigo, palpitations, flushing, hypotension (and effects related to hypotension), cough, dyspnoea, gastro-intestinal disorders (abdominal pain, constipation, diarrhoea, dyspepsia, nausea, vomiting, change of bowel habit), pruritus, rash, rash maculo-papular, muscle spasms, ankle swelling, asthenia, oedema and fatigue