Download Cosyrel 5 mg/5 mg, 5 mg/10 mg, 10 mg/5 mg, 10 mg/10 mg film

COMPOSITION*: Cosyrel 5 mg/5 mg, 5 mg/10 mg, 10 mg/5 mg, 10 mg/10 mg film-coated tablets contain 5 mg bisoprolol fumarate (bis)/5 mg perindopril arginine (per), 5 mg bis/10 mg per, 10 mg bis/5 mg per, 10 mg bis/10
mg per. INDICATIONS*: Cosyrel is indicated as substitution therapy for treatment of hypertension and/or stable coronary artery disease (in patients with a history of myocardial infarction and/or revascularisation) and/or stable chronic
heart failure with reduced systolic left ventricular function (Cosyrel 5 mg/5 mg and 10 mg/5 mg only) in adult patients adequately controlled with bisoprolol and perindopril given concurrently at the same dose level. DOSAGE AND ADMINISTRATION*: The usual posology is one tablet once daily. Patients should be stabilized with bisoprolol and perindopril at the same dose level for at least 4 weeks. The fixed dose combination is not suitable for initial therapy. For patients
stabilized with bisoprolol 2.5 mg and perindopril 2.5 mg or bisoprolol 2.5 mg and perindopril 5 mg: one half 5 mg/5 mg or 5 mg/10 mg tablet once daily. If a change of posology is required, titration should be done with the individual
components. Renal impairment: In patients with renal impairment, the recommended dose should be based on creatinine clearance. 5 mg/5 mg: Cl CR ≥ 60 (ml/min): 1 tablet; 30 < ClCR < 60: ½ tablet; ClCR < 30: not suitable, individual dose
titration with monocomponents recommended. 5 mg/10 mg: ClCR ≥ 60: ½ tablet; ClCR < 60: not suitable. 10 mg/5 mg: ClCR ≥ 60: 1 tablet; ClCR < 60: not suitable. 10 mg/10 mg: not suitable. Hepatic impairment: no dosage adjustment.
Elderly: administration according to the renal function. Paediatric population: safety and efficacy have not been established. Use is not recommended CONTRAINDICATIONS*: Hypersensitivity to the active substances, or to any of the
excipients, or to any other ACE inhibitor; acute heart failure or during episodes of heart failure decompensation requiring i.v. inotropic therapy; cardiogenic shock; second or third degree AV block (without pacemaker); sick sinus syndrome; sinoatrial block; symptomatic bradycardia; symptomatic hypotension; severe bronchial asthma or severe chronic obstructive pulmonary disease; severe forms of peripheral arterial occlusive disease or severe forms of Raynaud’s syndrome; untreated phaeochromocytoma (see section WARNINGS*); metabolic acidosis; history of angioedema associated with previous ACE inhibitor therapy; hereditary or idiopathic angioedema; second and third trimesters of pregnancy (see sections
WARNINGS*, PREGNANCY* and BREASTFEEDING*); concomitant use with aliskiren-containing products in patients with diabetes mellitus or renal impairment (GFR < 60 ml/min/1.73 m²) (see sections WARNINGS*, INTERACTIONS* and
Pharmacodynamic properties*). WARNINGS*: Hypotension: initiation should be closely monitored in patients who have been volume depleted, who have severe renin-dependent hypertension, with symptomatic heart failure, with or without
associated renal insufficiency, with ischaemic heart or cerebrovascular disease. A transient hypotensive response is not a contraindication to further doses once the blood pressure has increased after volume expansion. Hypersensitivity/Angioedema/Intestinal angioedema: stop treatment and monitor until complete resolution of symptoms. Therapy with beta-blocker must be continued. Angioedema associated with laryngeal oedema may be fatal. Hepatic failure: rarely, ACE inhibitors
have been associated with a syndrome that starts with cholestatic jaundice and progresses to fulminant hepatic necrosis and (sometimes) death: treatment should be discontinued if jaundice or marked elevations of hepatic enzymes. Black
people: perindopril may be less effective and cause a higher rate of angioedema than in non-black. Non-productive cough. Hyperkalaemia: frequent monitoring of serum potassium if renal insufficiency, worsening of renal function, age (>70
years), diabetes mellitus, dehydratation, acute cardiac decompensation, metabolic acidosis, and concomitant use of potassium-sparing diuretics, potassium supplements, potassium-containing salt substitutes, drugs associated with increases in
serum potassium. Combination with lithium, potassium sparing drugs, potassium supplements, potassium-containing salt substitutes, calcium antagonists, Class I antiarrhytmic drugs, centrally acting antihypertensive drugs: not recommended.
Dual blockade of the renin-angiotensin-aldosterone system (RAAS): concomitant use of ACE-inhibitors, angiotensin II receptor blockers or aliskiren increases the risk of hypotension, hyperkalaemia and decreased renal function (including acute
renal failure). Dual blockade of RAAS is therefore not recommended. ACE-inhibitors and angiotensin II receptor blockers should not be used concomitantly in patients with diabetic nephropathy. Stopping treatment: abrupt cessation should be
avoided. The posology should be decreased gradually, using the individual components, ideally over a period of two weeks. Bradycardia: if resting heart rate drops below 50-55 beats/min and symptoms related to bradycardia, dose should be
downtitrated using the individual components with an appropriate dose of bisoprolol. Patients with first degree AV block, aortic and mitral valve stenosis, hypertrophic cardiomyopathy, diabetes, strict fasting: use with caution. Patients with
Prinzmetal’s angina: Beta-blockers may increase the number and the duration of angina episodes. Renal impairment: daily dose should be adjusted on creatinine clearance. Monitor potassium and creatinine. In patients with bilateral renal artery
stenosis or stenosis of the artery to a solitary kidney, increases in blood urea and serum creatinine have been seen; with renovascular hypertension, increased risk of severe hypotension and renal insufficiency. Patients with recent kidney
transplantation, treated for heart failure with insulin dependent diabetes mellitus (type I), severely impaired renal function, severely impaired hepatic function, restrictive cardiomyopathy, congenital heart disease, haemodynamically significant
organic valvular disease, or myocardial infarction within the last 3 months: no experience. Anaphylactoid reactions: reported in patients dialysed with high flux membranes; during LDL apheresis with dextran sulphate, rarely, patients have experienced life-threatening anaphylactoid reactions, temporarily withhold therapy prior to each apheresis; during desensitization treatment, when ACE inhibitor temporarily withheld, these reactions have been avoided, but reappeared upon inadvertent rechallenge. Neutropenia/agranulocytosis/thrombocytopenia/anaemia: extreme caution in patients with collagen vascular disease, immunosuppressant therapy, treated with allopurinol or procainamide, periodic monitor of white blood
cell counts advised. Bronchospasm (bronchial asthma, obstructive airways diseases): bronchodilating therapy should be given concomitantly. Anaesthesia: if it is necessary to withdraw beta-blocker before surgery, this should be done gradually
and completed about 48 hours before anaesthesia. Treatment should be dicontinued one day prior to surgery. Psoriasis: carefully balance the benefits/risks. Phaeochromocytoma: bisoprolol should be given with an alpha-receptor blocker.
Thyreotoxicosis: symptoms may be masked. Pregnancy: stop treatment. If appropriate, start alternative therapy. INTERACTIONS*: Contra-indicated: Aliskiren in diabetic or impaired renal patients. Not recommended: Centrally acting antihypertensives such as clonidine and others (e.g. methyldopa, moxonidine, rilmenidine), Class I antiarrhythmic drugs (e.g. quinidine, disopyramide; lidocaine, phenytoin; flecainide, propafenone), Calcium antagonists of the verapamil type and to
a lesser extent of the diltiazem type, Aliskiren, concomitant therapy with ACE inhibitor and angiotensin-receptor blocker, Estramustine, Potassium sparing diuretics (e.g. triamterene, amiloride...), Potassium (salts), Lithium. Requiring special
care: Antidiabetic agents (insulins, oral hypoglycaemic agents), Non-steroidal anti-inflammatory medicinal products (NSAIDs) (including aspirin ≥ 3 g/day), antihypertensive agents and vasodilators, Tricyclic antidepressants/Antipsychotics/
Anesthetics, Sympathomimetics, Calcium antagonists of the dihydropyridine type such as felodipine and amlodipine, Class-III antiarrhythmic drugs (e.g. amiodarone), parasympathomimetic drugs, Topical beta-blockers (e.g. eye drops for
glaucoma treatment), Digitalis glycosides, Baclofen, Non-potassium-sparing diuretics, Potassium-sparing diuretics (eplerenone, spironolactone). To be taken into consideration: Mefloquine, Monoamine oxidase inhibitors (except MAO-B inhibitors),
Gliptins (linagliptin, saxagliptin, sitagliptin, vildagliptin), Gold. PREGNANCY AND BREASTFEEDING*: Not recommended during the first trimester of pregnancy and lactation. Contraindicated during the second and third trimesters of
pregnancy. FERTILITY*. DRIVE AND USE MACHINES*: Reactions related to low blood pressure may occur in some patients. The ability to drive or operate machinery may be impaired. UNDESIRABLE EFFECTS*: Very Common:
bradycardia. Common: headache, dizziness, vertigo, dysgeusia, paraesthesia, visual impairment, tinnitus, worsening of heart failure, hypotension and effects related to hypotension, feeling of coldness or numbness in the extremities, cough,
dyspnoea, abdominal pain, constipation, diarrhoea, nausea, vomiting, dyspepsia, rash, pruritus, muscle cramps, asthenia, fatigue. Uncommon: eosinophilia, hypoglycaemia, hyperkalaemia, hyponatraemia, mood altered, sleep disorder, depression, somnolence, syncope, palpitations, tachycardia, AV-conduction disturbances, orthostatic hypotension, vasculitis, bronchospasm, dry mouth, angioedema of face, extremities, lips, mucous membranes, tongue, glottis and/or larynx, urticaria, photosensitivity reactions, pemphigoid, hyperhidrosis, muscular weakness, arthralgia, myalgia, renal insufficiency, erectile dysfunction, chest pain, malaise, oedema peripheral, pyrexia, blood urea increased, blood creatinine increased, fall.
Rare: rhinitis, nightmares, hallucinations, reduced tear flow, hearing disorders, hepatitis either cytolytic or cholestatic, hypersensitivity reactions (itching, flush, rash), potency disorders, hepatic enzyme increased, blood bilirubin increased, increased
triglycerides. Very rare: agranulocytosis, pancytopenia, leukopenia, neutropenia, thrombocytopenia, haemolytic anaemia in patients with a congenital deficiency of G-6PDH, confusion, conjunctivitis, arrhythmia, angina pectoris, myocardial infarction and stroke possibly secondary to excessive hypotension in high-risk patients, eosinophilic pneumonia, pancreatitis, erythema multiform, alopecia, beta-blockers may provoke or worsen psoriasis or induce psoriasis-like rash, renal failure
acute, haemoglobin decreased and haematocrit decreased. OVERDOSE*. PROPERTIES*: Bisoprolol is a highly beta1-selective-adrenoceptor blocking agent, lacking intrinsic stimulating and relevant membrane stabilising activity. Perindopril
is an inhibitor of the enzyme that converts angiotensin I into angiotensin II (ACE). PRESENTATION*: Tablet container of 30 film-coated tablets of Cosyrel 5 mg/5 mg, 5 mg/10 mg, 10 mg/5 mg, 10 mg/10 mg. LES LABORATOIRES
SERVIER, 50 rue Carnot, 92284 Suresnes Cedex, France. www.servier.com * For complete information, please refer to the Summary of Product Characteristics for your country.