Triplixam

Per 5 mg/1.25 mg/5 mg FC tab Perindopril arginine 5 mg, indapamide 1.25 mg, amlodipine 5 mg. Per 5 mg/1.25 mg/10 mg FC tab Perindopril arginine 5 mg, indapamide 1.25 mg, amlodipine 10 mg. Per 10 mg/2.5 mg/10 mg Perindopril arginine 10 mg, indapamide 2.5 mg, amlodipine 10 mg

Substitution therapy for treatment of essential HTN, in patients already controlled w/ combination of perindopril, indapamide & amlodipine taken at the same dose level.

1 tab daily preferably in the morning. If change of posology is required, titration should be done w/ the individual components.

Should be taken on an empty stomach: Take before a meal.

Hypersensitivity to perindopril arginine, indapamide, amlodipine, other sulfonamides, dihydropyridine derivatives, any other ACE inhibitor. Dialysis patients. Patients w/ untreated decompensated heart failure. History of angioedema (Quincke’s oedema) associated w/ previous ACE inhibitor therapy. Hereditary/idiopathic angioedema. Hypokalaemia. Severe hypotension. Shock, including cardiogenic shock. Obstruction of the outflow tract of the left ventricle (eg, high grade aortic stenosis). Haemodynamically unstable heart failure after acute MI. Concomitant use of Triplixam w/ aliskiren-containing products in patients w/ DM or renal impairment (GFR <60 mL/min/1.73 m²), concomitant use w/ sacubitril/valsartan therapy. Triplixam must not be initiated earlier than 36 hr after the last dose of sacubitril/valsartan, extracorporeal treatments leading to contact of blood w/ negatively charged surfaces, significant bilateral renal artery stenosis or stenosis of the artery to a single functioning kidney. Severe renal impairment (CrCl <30 mL/min). Moderate renal impairment (CrCl <60 mL/min) for Triplixam 10 mg/2.5 mg/10 mg. Hepatic encephalopathy. Severe hepatic impairment. 2nd & 3rd trimesters of pregnancy.

Not suitable for initial therapy. Dual blockade of RAAS: ACE inhibitors & ARBs should not be used concomitantly in patients w/ diabetic nephropathy. Neutropenia/agranulocytosis/thrombocytopenia/anaemia: Caution if collagen vascular disease, immunosuppressant therapy, treatment w/ allopurinol or procainamide, or combination of these complicating factors, especially if pre-existing impaired renal function. Monitoring of WBC counts. Renovascular HTN: Increased risk of hypotension & renal insufficiency in patient w/ bilateral renal artery stenosis or stenosis of the artery to a single functioning kidney. Diuretics may be a contributory factor. Loss of renal function may occur (minor changes in serum creatinine) even in patients w/ unilateral renal artery stenosis. Hypersensitivity/angioedema, intestinal angioedema: Stop treatment & monitor until complete resolution of symptoms. Angioedema associated w/ laryngeal oedema may be fatal. Combination w/ sacubitril/valsartan (contraindicated due to the increased risk of angioedema). Sacubitril/valsartan must not be initiated until 36 hr after taking the last dose of perindopril therapy. Perindopril therapy must not be started until 36 hr after the last dose of sacubitril/valsartan. Concomitant use of ACE inhibitors w/ NEP inhibitors (eg, racecadotril), mTOR inhibitors (eg, sirolimus, everolimus, temsirolimus) & gliptins (eg, linagliptin, saxagliptin, sitagliptin, vildagliptin) may lead to an increased risk of angioedema (eg, swelling of the airways or tongue, w/ or w/o resp impairment). Caution should be used when starting racecadotril, mTOR inhibitors (eg, sirolimus, everolimus, temsirolimus) & gliptins (eg, linagliptin, saxagliptin, sitagliptin, vildagliptin) in a patient already taking an ACE inhibitor. Anaphylactoid reactions during desensitization: Caution in allergic patients treated w/ desensitization & avoid if venom immunotherapy. Temporarily w/drawal of ACE inhibitor at least 24 hr before desensitization. Anaphylactoid reactions during LDL apheresis: Temporarily w/holding ACE inhibitor prior to each apheresis. Haemodialysis patients: Consideration to use dialysis membranes other than high flux or antihypertensive agents other than ACE inhibitors. Primary aldosteronism: Use not recommended in patients w/ primary hyperaldosteronism (not responding to drugs acting through inhibition of the renin-angiotensin system). Pregnancy: No initiation during pregnancy, stop treatment & start alternative therapy if appropriate. Hepatic encephalopathy which can progress to hepatic coma: Stop treatment. Photosensitivity: Stop treatment. Renal function: In certain hypertensive patients w/o pre-existing apparent renal lesions & for whom renal blood tests show renal insufficiency, stop treatment & restart at a low dose or w/ 1 constituent only. Monitoring of K & creatinine, after 2 wk of treatment & then every 2 mth during therapeutic stability period. If bilateral renal artery stenosis or single functioning kidney: Not recommended. Risk of arterial hypotension &/or renal insufficiency (in cases of cardiac insufficiency, water & electrolyte depletion, in patients w/ low BP, renal artery stenosis, CHF or cirrhosis w/ oedema & ascites): Start treatment at low doses & increase progressively. Hypotension & water & Na depletion: Risk of sudden hypotension in presence of pre-existing Na depletion (in particular if renal artery stenosis): Monitoring of plasma electrolytes, re-establish blood vol & pressure, restart treatment at a reduced dose or w/ only 1 of the constituents. Na levels: More frequent monitoring in elderly & cirrhotic patients. K levels: Hyperkalaemia: Monitoring of serum K if renal insufficiency, worsening of renal function, age (>70 yr), DM, intercurrent events, in particular dehydration, acute cardiac decompensation, metabolic acidosis & concomitant use of K-sparing diuretics, K supplements or K salts, or other drugs associated w/ increases in serum K & especially aldosterone antagonists or ARBs. Hypokalaemia: High risk for elderly &/or malnourished subjects, cirrhotic patients w/ oedema & ascites, coronary patients, patients w/ renal failure or heart failure, long QT interval: Monitoring of serum K, may cause muscle disorders & rhabdomyolysis, may favor the onset of Torsades de pointes, which may be fatal: Associated w/ hypomagnesaemia can be refractory to treatment unless serum Mg is corrected. Ca levels: Hypercalcemia: Stop treatment before investigating the parathyroid function. Renovascular HTN: If renal artery stenosis: Start treatment at hospital at low dose; monitor renal function & K. Dry cough. Atherosclerosis: Start treatment at low dose in patients w/ ischaemic heart disease or cerebral circulatory insufficiency. Hypertensive crisis. Cardiac failure/severe cardiac insufficiency: Caution if heart failure. Severe cardiac insufficiency (grade IV): Start treatment under medical supervision w/ reduced initial dose. Aortic or mitral valve stenosis/hypertrophic cardiomyopathy: Caution if obstruction in the outflow tract of the left ventricle. Diabetic patients: If IDDM, start treatment under medical supervision w/ reduced initial dose; monitor blood glucose during the 1st mth &/or in the case of hypokalaemia. Black people: Higher incidence of angioedema & apparently less effective in lowering BP than in non-Blacks. Surgery/anaesth: Stop treatment 1 day before surgery. Hepatic impairment: Mild to moderate: Caution. Rarely, ACE inhibitors have been associated w/ a syndrome that starts w/ cholestatic jaundice & progresses to fulminant hepatic necrosis & (sometimes) death. Stop treatment if jaundice or marked elevations of hepatic enzymes. Uric acid: Hyperuricemia: Increased tendency to gout attacks. Excipients: Na-free. Choroidal effusion, acute myopia & secondary angle-closure glaucoma: Discontinue drug intake as rapidly as possible. Prompt medical or surgical treatments may need to be considered if the IOP remains uncontrolled. Athletes: May cause +ve doping test. Should not be used in paed population. Elderly: Testing of renal function & K levels before treatment start. Dosage increase w/ care.

Hypokalaemia, dizziness, headache, paraesthesia, vertigo, somnolence, dysgeusia, visual impairment, diplopia, tinnitus, palpitations, flushing, hypotension (& effects related to hypotension), cough, dyspnoea, abdominal pain, constipation, diarrhoea, dyspepsia, nausea, vomiting, change of bowel habit, pruritus, rash, rash maculopapular, muscle spasms, ankle swelling, asthenia, fatigue. Rhinitis, eosinophilia, hypersensitivity, hypoglycaemia, hyperkalaemia reversible on discontinuation, hyponatraemia, insomnia, mood altered (including anxiety), depression, sleep disorder, hypoaesthesia, tremor, syncope, tachycardia, arrhythmia (including bradycardia, ventricular tachycardia & atrial fibrillation), vasculitis, bronchospasm, dry mouth, urticaria, angioedema, alopecia, purpura, skin discoloration, hyperhidrosis, exanthema, photosensitivity reaction, pemphigoid, arthralgia, myalgia, back pain, micturition disorder, nocturia, pollakiuria, renal failure, erectile dysfunction, gynaecomastia, pain, chest pain, malaise, oedema peripheral, pyrexia, wt increased, wt decreased, blood urea increased, blood creatinine increased, fall. SIADH, anuria/oliguria, acute renal failure, hypochloraemia, hypomagnesaemia, confusional state, blood bilirubin increased, hepatic enzyme increased, psoriasis aggravation. Agranulocytosis, aplastic anaemia, pancytopenia, leukopenia, neutropenia, haemolytic anaemia, thrombocytopenia, allergic reactions, hyperglycaemia, hypercalcaemia, hypertonia, neuropathy peripheral, stroke possibly secondary to excessive hypotension in high-risk patients, angina pectoris, MI, possibly secondary to excessive hypotension in high risk patients, eosinophilic pneumonia, gingival hyperplasia, pancreatitis, gastritis, hepatitis, jaundice, hepatic function abnormal, erythema multiforme, SJS, exfoliative dermatitis, TEN, Quincke’s oedema, haemoglobin decreased & haematocrit decreased. Extrapyramidal disorder (extrapyramidal syndrome), myopia, vision blurred, acute angle-closure glaucoma, choroidal effusion, Torsades de pointes (potentially fatal), rhabdomyolysis, muscular weakness, possibility of onset of hepatic encephalopathy in case of hepatic insufficiency, possible worsening of pre-existing SLE, ECG QT prolonged, blood glucose increased, blood uric acid increased. Raynaud’s phenomenon.

Drugs increasing risk of angioedema: Sacubitril/valsartan, racecadotril, mTOR inhibitors (eg, sirolimus, everolimus, temsirolimus), & gliptins (eg, linagliptin, saxagliptin, sitagliptin, vildagliptin). Drugs inducing hyperkalaemia: Aliskiren, K salts, K-sparing diuretics, ACE inhibitors, AIIA, NSAIDs, heparins, immunosuppressant agents eg, ciclosporin or tacrolimus, trimethoprim & co-trimoxazole (trimethoprim/sulfamethoxazole). Contraindicated: Aliskiren in diabetic or impaired renal patients, extracorporeal treatments. Not recommended: Lithium, aliskiren in patients other than diabetic or impaired renal patients, concomitant therapy w/ ACE inhibitor & ARB, estramustine, K-sparing drugs (eg, triamterene, amiloride), K salts, dantrolene (infusion), grapefruit or grapefruit juice. Special care: Baclofen, NSAIDs (included ASA at high doses), antidiabetic agents (insulin, hypoglycaemic agents), non-K-sparing diuretics & K-sparing diuretics (eplerenone, spironolactone), Torsades de pointes inducing drugs, amphotericin B (IV route), glucocorticoids & mineralocorticoids (systemic route), tetracosactide, stimulant laxatives, cardiac glycosides, allopurinol, CYP3A4 inducers, CYP3A4 inhibitors. To be taken into consideration: Imipramine-like antidepressants (tricyclics), neuroleptics, other antihypertensive agents & vasodilatators, tetracosactide, allopurinol, cytostatic or immunosuppressive agents, systemic corticosteroids or procainamide, anaesth drugs, diuretics (thiazide or loop diuretics), sympathomimetics, gold, metformin, iodinated contrast media, Ca (salts), ciclosporin, atorvastatin, digoxin, warfarin, tacrolimus, simvastatin, mTOR inhibitors.

ACE Inhibitors/Direct Renin Inhibitors / Calcium Antagonists / Diuretics

C09BX01 - perindopril, amlodipine and indapamide ; Belongs to the class of ACE inhibitors and other combinations. Used in the treatment of cardiovascular disease.

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