Cosyrel

Substitution therapy in adult patients adequately controlled w/ bisoprolol & perindopril given concurrently at same dose level for: HTN; stable CAD (in patients w/ history of MI &/or revascularization); stable chronic heart failure w/ reduced systolic left ventricular function (5 mg/5 mg only).

1 tab once daily. Stabilize at the same dose level for at least 4 wk. Fixed dose combination not suitable for initial therapy. If change of posology is required, titration w/ individual components. Elderly Administer according to renal function. Renal impairment Individual dose titration w/ monocomponent is recommended.

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

Hypersensitivity to bisoprolol, perindopril or other ACE inhibitors. Acute heart failure or during episodes of heart failure decompensation requiring IV inotropic therapy; cardiogenic shock; 2nd or 3rd degree AV block (w/o pacemaker); sick sinus syndrome; SA block; symptomatic bradycardia & hypotension; severe bronchial asthma or COPD; severe forms of peripheral arterial occlusive disease or Raynaud's syndrome; untreated phaeochromocytoma; metabolic acidosis; history of angioedema associated w/ previous ACE inhibitor therapy; hereditary or idiopathic angioedema. Concomitant use w/ aliskiren-containing products in patients w/ DM or renal impairment (GFR <60 mL/min/1.73 m²); sacubitril/valsartan. Extracorporeal treatments leading to blood contact w/ -vely charged surfaces. Significant bilateral renal artery stenosis or artery stenosis to a single functioning kidney. Pregnancy (2nd & 3rd trimesters).

Hypersensitivity/angioedema. Anaphylactoid reactions may occur in patients dialysed w/ high flux membranes & treated concomitantly w/ ACE inhibitors; during LDL apheresis & desensitisation. Closely monitor patients at risk of symptomatic hypotension during therapy initiation and dose adjustments. Dose reduction or gradual discontinuation of treatment using individual components may be necessary if hypotension becomes symptomatic. Not to initiate sacubitril/valsartan until 36 hr after last dose. Concomitant use w/ NEP inhibitors eg, racecadotril; mTOR inhibitors eg, sirolimus, everolimus, temsirolimus; gliptins eg, linagliptin, saxagliptin, sitagliptin, vildagliptin. Discontinue use if jaundice or marked hepatic enzymes elevations occur. Higher rate of angioedema in Black patients. Not recommended in combination w/ lithium, K-sparing drugs, K supplements or K-containing salt substitutes; Ca antagonists, class I antiarrhythmics, centrally acting antihypertensives. Dual blockade of renin-angiotensin-aldosterone system (RAAS) through combined use of ACE inhibitors, ARBs or aliskiren is not recommended. Frequently monitor renal function, electrolyte & BP. Do not use concomitantly in patients w/ diabetic nephropathy. Avoid abrupt cessation of therapy w/ β-blocker. Non-productive, persistent cough; hyperkalaemia; bradycardia; 1st degree AV block; aortic & mitral valve stenosis/hypertrophic cardiomyopathy; Prinzmetal's angina; recent kidney transplantation; bronchospasm; DM; patient w/ strict fasting; psoriasis or history of psoriasis; known or suspected phaeochromocytoma; IDDM, restrictive cardiomyopathy, congenital heart disease, haemodynamically significant organic valvular disease, MI w/in last 3 mth. Increased risk of hypotension & renal insufficiency in patients w/ bilateral renal artery stenosis or stenosis of the artery to a single functioning kidney. Patients w/ collagen vascular disease, immunosuppressant therapy, treatment w/ allopurinol or procainamide. Periodically monitor WBC counts during therapy. May mask symptoms of hypoglycaemia; thyreotoxicosis. Aggravation of peripheral arterial occlusive disease symptoms may occur when starting therapy. Discontinue 1 day prior to surgery in patients undergoing major surgery or during anaesth. Not recommended in patients w/ primary hyperaldosteronism. May impair ability to drive or operate machinery. Severe renal & hepatic impairment. Not recommended during 1st trimester of pregnancy & lactation. Not recommended in childn & adolescents. Elderly.

Headache, dizziness; hypotension & effects related to hypotension; abdominal pain, constipation, diarrhoea, nausea, vomiting; asthenia. Bisprolol: Bradycardia. Worsening of heart failure; feeling of coldness or numbness in the extremities; fatigue. Perindopril: Vertigo, dysgeusia, paraesthesia; visual impairment; tinnitus; cough, dyspnoea; dyspepsia; rash, pruritus; muscle cramps.

Increased risk of angioedema w/ sacubitril/valsartan, racecadotril, mTOR inhibitors (eg, sirolimus, everolimus, temsirolimus), gliptins (linagliptin, saxagliptin, sitagliptin, vildagliptin). Increased risk of hyperkalaemia w/ aliskiren, K salts, K-sparing diuretics (eg, spironolactone, triamterene or amiloride), ACE inhibitors, AIIA, NSAIDs, heparins, immunosuppressant agents eg, ciclosporin or tacrolimus, trimethoprim & co-trimoxazole (trimethoprim/sulfamethoxazole). Increased risk of hyperkalaemia, worsened renal function, CV morbidity & mortality w/ aliskiren. Increased risk of severe anaphylactoid reactions w/ extracorporeal treatments eg, dialysis or haemofiltration. Increased blood-glucose lowering effects w/ antidiabetics (eg, insulin, oral hypoglycemics). Attenuated antihypertensive effects w/ NSAIDs eg, ASA, COX-2 inhibitors & non-selective NSAIDs. Increased hypotensive effects w/ antihypertensive agents, vasodilators (eg, nitroglycerin, other nitrates or other vasodilators) or other BP-reducing medications (eg, TCAs, barbiturates, phenothiazines). Reduced BP w/ anaesth medicinal products, TCAs, antipsychotics. Reduced reflex tachycardia & increased risk of hypotension w/ anaesth. Reduced effects w/ β-sympathomimetics (eg, isoprenaline, dobutamine). Increased BP & exacerbated intermittent claudication w/ β- & α-adrenoceptors (eg, norepinephrine, epinephrine). Bisoprolol: May worsen heart failure w/ centrally acting antihypertensives (eg, clonidine, methyldopa, moxonidine, rilmenidine). Potentiated AV conduction time & -ve inotropic effect w/ class I antiarrhythmics (eg, quinidine, disopyramide; lidocaine, phenytoin; flecainide, propafenone). Negative influence on contractility & AV conduction w/ verapamil- & diltiazem-type Ca antagonists. Increased risk of hypotension & ventricular pump function deterioration w/ dihydropyridine-type Ca antagonists (eg, felodipine, amlodipine). Potentiated AV conduction time w/ class III antiarrhythmics (eg, amiodarone). Increased AV conduction time & risk of bradycardia w/ parasympathomimetic drugs. Additive systemic effects w/ topical β-blockers (eg, eye drops for glaucoma treatment). Reduced heart rate & increased AV conduction time w/ digitalis glycosides. Increased risk of bradycardia w/ mefloquine. Enhanced hypotensive effects w/ MAOIs (except MAO-B inhibitors). Perindopril: Higher frequency of adverse events w/ ACE inhibitor & ARBs. Increased risk of angioedema w/ estramustine. Reversible increase in serum lithium conc & toxicity. Increased antihypertensive effect w/ baclofen. Excessive reduction in BP w/ non-K-sparing diuretics. Risk of hyperkalaemia w/ K-sparing diuretics (eg, eplerenone, spironolactone). Nitritoid reactions w/ injectable gold (Na aurothiomalate).

ACE Inhibitors/Direct Renin Inhibitors / Beta-Blockers

C09BX02 - perindopril and bisoprolol ; Belongs to the class of ACE inhibitors and other combinations. Used in the treatment of cardiovascular disease.

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