Candesartan STELLA 8 mg

Rx

Indications

• Essential hypertension in adults.
• Adult patients with heart failure and impaired left ventricular systolic function (left ventricular ejection fraction ≤ 40%) when angiotensin converting enzyme (ACE) inhibitors are not tolerated or as add-on therapy to ACE inhibitors in patients with symptomatic heart failure, despite optimal therapy, when mineralocorticoid receptor antagonists are not tolerated.
• Hypertension in children and adolescents aged 6 to < 18 years.

Dosage

Hypertension

• The recommended initial dose and usual maintenance dose: 8 mg once daily. Most of the antihypertensive effect is attained within 4 weeks. In some patients whose blood pressure is not adequately controlled, the dose can be increased to 16 mg once daily and to a maximum of 32 mg once daily. Therapy should be adjusted according to blood pressure response.
• Candesartan may also be administered with other antihypertensive agents. Addition of hydrochlorothiazide has been shown to have an additive antihypertensive effect with various doses of candesartan.
• No initial dose adjustment is necessary in elderly patients.
• Intravascular volume depletion
  An initial dose of 4 mg may be considered in patients at risk for hypotension, such as patients with possible volume depletion.
• Renal impairment
  The starting dose is 4 mg in patients with renal impairment, including patients on haemodialysis. The dose should be titrated according to response. There is limited experience in patients with very severe or end-stage renal impairment (Creatinine clearance < 15 ml/min).
• Hepatic impairment
  An initial dose of 4 mg once daily is recommended in patients with mild to moderate hepatic impairment. The dose may be adjusted according to response. Candesartan is contraindicated in patients with severe hepatic impairment and/or cholestasis.
• Paediatric population:
  Children and adolescents aged 6 to < 18 years: The recommended starting dose is 4 mg once daily.
  For patients weighing < 50 kg: The dose can be increased to a maximum of 8 mg once daily.
  For patients weighing ≥ 50 kg: The dose can be increased to 8 mg once daily and then to 16 mg once daily if needed.
  Doses above 32 mg have not been studied in paediatric patients. Most of the antihypertensive effect is attained within 4 weeks.
  For children with possible intravascular volume depletion (e.g., patients treated with diuretics, particularly those with impaired renal function), candesartan treatment should be initiated under close medical supervision and a lower starting dose than the general starting dose above should be considered.
  Candesartan has not been studied in children with glomerular filtration rate less than 30 ml/min/1.73 m².
  Safety and efficacy of the drug in children aged 1 to < 6 years of age has not been established. No recommendations can be made from the available data.
  Candesartan is contraindicated in children aged < 1 year.

Heart failure

• The usual recommended initial dose of candesartan is 4 mg once daily.
  Up-titration to the target dose of 32 mg once daily (maximum dose) or the highest tolerated dose is done by doubling the dose at intervals of at least 2 weeks. Evaluation of patients with heart failure should always comprise assessment of renal function including monitoring of serum creatinine and potassium.
• Candesartan can be administered with other heart failure treatment, including ACE inhibitors, beta-blockers, diuretics and digitalis or a combination of these medicinal products.
• Candesartan may be co-administered with an ACE-inhibitor in patients with symptomatic heart failure.
• The combination of an ACE inhibitor, a potassium-sparing diuretic (e.g. spironolactone) and candesartan is not recommended and should be considered only after careful evaluation of the potential benefits and risks.
• No initial dose adjustment is necessary for elderly patients or in patients with intravascular volume depletion or renal impairment or mild to moderate hepatic impairment.
• The safety and efficacy of candesartan in children aged between birth and 18 years have not been established in the treatment of heart failure.

Usage

Candesartan STELLA 8 mg is administered orally. The drugs should be taken once daily with or without food.

• Hypersensitive to candesartan cilexetil or to any of the ingredients.
• Second and third trimesters of pregnancy.
• Severe hepatic impairment and/or cholestasis.
• Children aged below 1 year.
• The concomitant use of candesartan celexetil with aliskiren-containing products is contraindicated in patients with diabetes mellitus or renal impairment (GFR < 60 ml/min/1.73 m²).

Adverse reactions were mild and transient, no association with dose or age. The most commonly reported adverse reactions were dizziness/vertigo, headache and respiratory infection.

• 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). Dual blockade of RAAS through the combined use of ACE-inhibitors, angiotensin II receptor blockers or aliskiren is therefore not recommended.
  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.
• 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 (CrCl < 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.
• Use in paediatric patients including patients with renal impairment: Candesartan has not been studied in children with a glomerular filtration rate less than 30 ml/min/1.73 m².
• Concomitant therapy with an ACE-inhibitor in heart failure: The risk of adverse reactions, especially hypotension, hyperkalaemia and decreased renal function (including acute renal failure), may increase when candesartan is used in combination with an ACE-inhibitor. Triple combination of an ACE-inhibitor, a mineralocorticoid receptor antagonist and candesartan cilexetil is also not recommended. Use of these combinations should be 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.
• In patients on haemodialysis, candesartan should be carefully titrated with thorough monitoring of blood pressure.
• 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.
• There is no experience regarding the administration of candesartan in patients with a recent kidney transplantation.
• 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.
• For children with possible intravascular volume depletion (e.g. patients treated with diuretics, particularly those with impaired renal function), candesartan treatment should be initiated under close medical supervision and a lower starting dose should be considered.
• 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.
• Candesartan is not recommended in patients with primary hyperaldosteronism.
• Hyperkalaemia: Concomitant use of candesartan with potassium-sparing diuretics, potassium supplements, salt substitutes containing potassium, or other medicinal products that may increase potassium levels (e.g. heparin) 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. The combination of an ACE inhibitor, a potassium-sparing diuretic (e.g. spironolactone) and candesartan is not recommended and should be considered only after careful evaluation of the potential benefits and risks.
• General: In patients whose vascular tone and renal function depend predominantly on the activity of the renin-angiotensin-aldosterone system (e.g. patients with severe congestive heart failure or underlying renal disease, including renal artery stenosis), treatment with other medicinal products that affect this system has been associated with acute hypotension, azotaemia, oliguria or, rarely, acute renal failure. The possibility of similar effects cannot be excluded with AIIRAs. As with any antihypertensive agent, excessive blood pressure decrease in patients with ischaemic cardiopathy or ischaemic cerebrovascular disease could result in a myocardial infarction or stroke.
  The antihypertensive effect of candesartan may be enhanced by other medicinal products with blood pressure lowering properties.
• Candesartan STELLA 8 mg contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.
• Pregnancy: AIIRAs should not be initiated during pregnancy. Unless continued AIIRAs therapy is considered essential, patients planning pregnancy should be changed to alternative antihypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with AIIRAs should be stopped immediately, and, if appropriate, alternative therapy should be started.
  In post-menarche patients the possibility of pregnancy should be evaluated on a regular basis. Appropriate information should be given and/or action taken to prevent the risk of exposure during pregnancy.
• Candesartan is not recommended and alternative treatments with better established safety profiles during breast-feeding are preferable, especially while nursing a newborn or preterm infant.
• No studies on the effects of candesartan on the ability to drive and use machines have been performed. However, it should be taken into account that occasionally dizziness or weariness may occur during treatment with candesartan.