CANDESARTAN CILEXETIL /AMLODIPINE

Posology Patients should use the strength corresponding to their previous treatment. For the usual doses different strengths of this medicinal product are available. A dose of 8 mg candesartan cilexetil and 5 mg amlodipine daily is given as 1 tablet of Candesartan cilexetil/Amlodipine 8 mg/5 mg.

A dose of 16 mg candesartan cilexetil and 5 mg amlodipine daily is given as 1 tablet of Candesartan cilexetil/Amlodipine 16 mg/5 mg. A dose of 16 mg candesartan cilexetil and 10 mg amlodipine daily is given as 2 tablets of Candesartan cilexetil/Amlodipine 8 mg/5 mg or 1 tablet of Candesartan cilexetil/Amlodipine 16 mg/10 mg.

The maximum daily dose of candesartan cilexetil is 32 mg and the maximum daily dose of amlodipine is 10 mg. 2). Hepatic impairment Dosage recommendations for patients with impaired liver function have not been established. 2). 2). Monitoring of potassium levels and creatinine is advised in moderate renal impairment.

Paediatric population The safety and efficacy of Candesartan cilexetil/Amlodipine in children aged below 18 years has not yet been established. No data are available. Method of administration The tablets can be taken with or without food.

Adverse reactions previously reported with one of the individual components (amlodipine or candesartan) may be potential undesirable effects with Candesartan cilexetil/Amlodipine. Undesirable effects linked to amlodipine Summary of the safety profile The most commonly reported adverse reactions during treatment are somnolence, dizziness, headache, palpitations, flushing, abdominal pain, nausea, ankle swelling, oedema and fatigue.

The following adverse reactions have been observed and reported during treatment with amlodipine with the following frequencies: Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1 000 to ≤1/100); rare (≥1/10 000 to ≤1/1 000); very rare (≤1/10 000), not known (cannot be estimated from the available data).

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. System organ class Frequency Adverse reactions Blood and lymphatic system disorders Very rare Leukocytopenia, thrombocytopenia Immune system disorders Very rare Allergic reactions Metabolism and nutrition disorders Very rare Hyperglycaemia Uncommon Depression, mood changes (including anxiety), insomnia Psychiatric disorders Rare Confusion Common Somnolence, dizziness, headache (especially at the beginning of the treatment) Uncommon Tremor, dysgeusia, syncope, hypoaesthesia, paraesthesia Very rare Hypertonia, peripheral neuropathy Nervous system disorders Not known Extrapyramidal disorder Eye disorders Common Visual disturbance (including diplopia) Ear and labyrinth disorders Uncommon Tinnitus Common Palpitations Uncommon Arrhythmia (including bradycardia, ventricular tachycardia and atrial fibrillation) Cardiac disorders Very rare Myocardial infarction Common Flushing Uncommon Hypotension Vascular disorders Very rare Vasculitis Respiratory, thoracic Common Dyspnoea and mediastinal disorders Uncommon Cough, rhinitis Common Abdominal pain, nausea, dyspepsia, altered bowel habits (including diarrhoea and constipation) Uncommon Vomiting, dry mouth Gastrointestinal disorders Very rare Pancreatitis, gastritis, gingival hyperplasia Hepatobiliary disorders Very rare Hepatitis, jaundice, hepatic enzymes increased* Uncommon Alopecia, purpura, skin discolouration, hyperhidrosis, pruritus, rash, exanthema, urticaria Very rare Angioedema, erythema multiforme, exfoliative dermatitis, Stevens- Johnson syndrome, Quincke oedema, photosensitivity Skin and subcutaneous tissue disorders Not known Toxic epidermal necrolysis Common Ankle swelling, muscle crampsMusculoskeletal and connective tissue disorders Uncommon Arthralgia, myalgia, back pain Renal and urinary disorders Uncommon Micturition disorder, nocturia, increased urinary frequency Reproductive system and breast disorders Uncommon Impotence, gynecomastia Very common Oedema Common Fatigue, asthenia General disorders and administration site conditions Uncommon Chest pain, pain, malaise Investigations Uncommon Weight increased, weight decreased *mostly consistent with cholestasis Undesirable effects linked to candesartan Treatment of hypertension In controlled clinical studies adverse reactions were mild and transient.

The overall incidence of adverse events showed no association with dose or age. 2%). In a pooled analysis of clinical trial data of hypertensive patients, adverse reactions with candesartan cilexetil were defined based on an incidence of adverse events with candesartan cilexetil at least 1% higher than the incidence seen with placebo.

By this definition, the most commonly reported adverse reactions were dizziness/vertigo, headache and respiratory infection. The table below presents adverse reactions from clinical trials and post-marketing experience. 8 are: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1 000 to < 1/100), rare (≥ 1/10 000 to < 1/1 000) and very rare (< 1/10 000).

4) Laboratory findings In general, there were no clinically important influences of candesartan on routine laboratory variables. As for other inhibitors of the renin-angiotensin-aldosterone system, small decreases in haemoglobin have been seen.

No routine monitoring of laboratory variables is usually necessary for patients receiving candesartan cilexetil. However, in patients with renal impairment, periodic monitoring of serum potassium and creatinine levels is recommended.

Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

Amlodipine The safety and efficacy of amlodipine in hypertensive crisis has not been established. Cardiac failure Patients with heart failure should be treated with caution. 1). Calcium channel blockers, including amlodipine, should be used with caution in patients with congestive heart failure, as they may increase the risk of future cardiovascular events and mortality.

Hepatic impairment The half-life of amlodipine is prolonged and AUC values are higher in patients with impaired liver function; dosage recommendations have not been established. Amlodipine should therefore be initiated at the lower end of the dosing range and caution should be used, both on initial treatment and when increasing the dose.

3). 2). Renal failure Amlodipine may be used in such patients at normal doses. Changes in amlodipine plasma concentrations are not correlated with degree of renal impairment. Amlodipine is not dialysable. Candesartan Renal impairment As with other agents inhibiting the renin-angiotensin-aldosterone system, changes in renal function may be anticipated in susceptible patients treated with candesartan.

When candesartan is used in hypertensive patients with renal impairment, periodic monitoring of serum potassium and creatinine levels is recommended. There is limited experience in patients with very severe or end-stage renal impairment (Clcreatinine < 15 ml/min).

In these patients candesartan should be carefully titrated with thorough monitoring of blood pressure. Evaluation of patients with heart failure should include periodic assessments of renal function, especially in elderly patients 75 years or older, and patients with impaired renal function.

During dose titration of candesartan, monitoring of serum creatinine and potassium is recommended. Clinical trials in heart failure did not include patients with serum creatinine > 265 μmol/l (> 3 mg/dl). Dual blockade of the renin-angiotensin-aldosterone system (RAAS) There is evidence that the 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).

1). If dual blockade therapy is considered absolutely necessary, this should only occur under specialist supervision and subject to frequent close monitoring of renal function, electrolytes and blood pressure. ACE-inhibitors and angiotensin II receptor blockers should not be used concomitantly in patients with diabetic nephropathy.

Haemodialysis During dialysis the blood pressure may be particularly sensitive to AT1-receptor blockade as a result of reduced plasma volume and activation of the renin- angiotensin-aldosterone system. Therefore, candesartan should be carefully titrated with thorough monitoring of blood pressure in patients on haemodialysis.

Renal artery stenosis Medicinal products that affect the renin-angiotensin-aldosterone system, including angiotensin II receptor antagonists (AIIRAs), may increase blood urea and serum creatinine in patients with bilateral renal artery stenosis or stenosis of the artery to a solitary kidney.

Kidney transplantation There is limited clinical evidence regarding candesartan use in patients who have undergone renal transplant. Hypotension Hypotension may occur during treatment with candesartan in heart failure patients. It may also occur in hypertensive patients with intravascular volume depletion such as those receiving high dose diuretics.

Caution should be observed when initiating therapy and correction of hypovolemia should be attempted. Anaesthesia and surgery Hypotension may occur during anaesthesia and surgery in patients treated with angiotensin II antagonists due to blockade of the renin-angiotensin system.

Very rarely, hypotension may be severe such that it may warrant the use of intravenous fluids and/or vasopressors. Aortic and mitral valve stenosis (obstructive hypertrophic cardiomyopathy) As with other vasodilators, special caution is indicated in patients suffering from haemodynamically relevant aortic or mitral valve stenosis, or obstructive hypertrophic cardiomyopathy.

Primary hyperaldosteronism Patients with primary hyperaldosteronism will not generally respond to antihypertensive medicinal products acting through inhibition of the renin- angiotensin-aldosterone system. Therefore, the use of candesartan is not recommended in this population.

g. heparin, co-trimoxazole also known as trimethoprim/sulfamethoxazole) may lead to increases in serum potassium in hypertensive patients. Monitoring of potassium should be undertaken as appropriate. In heart failure patients treated with candesartan, hyperkalaemia may occur.

Periodic monitoring of serum potassium is recommended. g. spironolactone) and candesartan is not recommended and should be considered only after careful evaluation of the potential benefits and risks. 8). These patients presented with […]

1. - Severe hypotension. - Shock, including cardiogenic shock. g. high grade aortic stenosis). - Haemodynamically unstable heart failure after acute myocardial infarction. 6). - Severe hepatic impairment and/or cholestasis. 1).