Special Warning : אזהרת שימוש

4.4    Special warnings and precautions for use

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 (see section 4.5 and 5.1). 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.


Renal impairment
As with other agents inhibiting the renin-angiotensin-aldosterone system, changes in renal function may be anticipated in susceptible patients treated with Atacand.


When Atacand 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 (i.e., CLcreatinine<15 ml/min). In these patients Atacand 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 Atacand, monitoring of serum creatinine and potassium is recommended. Clinical trials in heart failure did not include patients with serum creatinine >265 mol/L (>3 mg/dL) 

Concomitant therapy with an ACE inhibitor in heart failure The risk of adverse reactions, especially hypotension, hyperkaaemia and decreased renal function (including acute renal failure), may increase when Atacand is used in combination with an ACE inhibitor. Triple combination of an ACE-inhibitor, a mineralocorticoid receptor antagonist and candesartan 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


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, Atacand 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 Atacand use in patients who have undergone renal transplant.


Hypotension
Hypotension may occur during treatment with Atacand 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 or 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 Atacand is not recommended in this population.


Hyperkalaemia
Concomitant use of Atacand with potassium-sparing diuretics, potassium supplements, salt substitutes containing potassium, or other medicinal products that may increase potassium levels (e.g. heparin and combination of trimetoprim/sulfametoxazol) may lead to increases in serum potassium in hypertensive patients. Monitoring of potassium should be undertaken as appropriate.


In heart failure patients treated with Atacand, hyperkalaemia may occur, periodic monitoring of serum potassium is recommended. The combination of an ACE- inhibitor, a potassium-sparing diuretic (e.g. spironolactone) and Atacand 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, whether prescribed as an antihypertensive or prescribed for other indications.


Atacand contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.


Pregnancy
AIIRAs should not be initiated during pregnancy. Unless continued AIIRA 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 (see sections 4.3 and 4.6).
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 (see sections 4.3 and 4.6)

Effects on Driving

4.7    Effects on ability to drive and use machines
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 Atacand.