Special Warning : אזהרת שימוש

4.4 Special warnings and precautions for use
Aliskiren should be used with caution in patients with serious congestive heart failure (New York Heart Association [NYHA] functional class III-IV).

In the event of severe and persistent diarrhoea, Rasilez therapy should be stopped.


RAS API JUN15 CL V10                                      REF CDS 6May14 & 18Dec14 Dual blockade of the renin-angiotensin-aldosterone system (RAAS)
Hypotension, syncope, stroke, hyperkalaemia, and decreased renal function (including acute renal failure) have been reported in susceptible individuals, especially if combining medicinal products that affect this system (see section 5.1). Dual blockade of the RAAS by combining aliskiren with an ACEI or an ARB 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.

Anaphylactic reactions and angioedema
Hypersensitivity reactions such as anaphylactic reactions and angioedema have been reported during treatment with aliskiren (see section 4.8). In controlled clinical trials, angioedema occurred rarely during treatment with aliskiren with rates comparable to treatment with placebo or hydrochlorothiazide. Anaphylactic reactions have been reported from post-marketing experience with unknown frequency. Special caution is necessary in patients with a predisposition for hypersensitivity. Patients should discontinue the treatment promptly and should be informed to report to the physician any signs suggesting allergic reactions (in particular, difficulties in breathing or swallowing, swelling of face, extremities, eyes, lips or tongue). Appropriate therapy and monitoring measures should be initiated.
Angioedema
As with other agents acting on the renin-angiotensin system, angioedema or symptoms suggestive of angioedema (swelling of the face, lips, throat and/or tongue) have been reported in patients treated with aliskiren.
A number of these patients had a history of angioedema or symptoms suggestive of angioedema, which in some cases followed use of other medicines that can cause angioedema, including RAAS blockers (ACEI orARBs) (see section 4.8).
Patients with a history of angioedema may be at increased risk of experiencing angioedema during treatment with aliskiren (see sections 4.3 and 4.8). Caution should therefore be exercised when prescribing aliskiren to patients with a history of angioedema, and such patients should be closely monitored during treatment (see section 4.8) especially at the beginning of treatment.
If angioedema occurs, Rasilez should be promptly discontinued and appropriate therapy and monitoring provided until complete and sustained resolution of signs and symptoms has occurred. Where there is involvement of the tongue, glottis or larynx adrenaline should be administered. In addition, measures necessary to maintain patient airways should be provided.


RAS API JUN15 CL V10                                     REF CDS 6May14 & 18Dec14 Risk of symptomatic hypotension
Symptomatic hypotension could occur after initiation of treatment with Rasilez in the following cases:
-   Patients with marked volume depletion or
-   Patients with salt depletion or
-   Combined use of aliskiren with other agents acting on the RAAS (see section 4.5) The volume- or salt depletion should be corrected prior to administration of Rasilez, or the treatment should start under close medical supervision.


Patients with pre-existing renal impairment
In clinical studies Rasilez has not been investigated in hypertensive patients with severe renal impairment (serum creatinine ≥ 150 μmol/l or 1.70 mg/dl in women and ≥ 177 μmol/l or 2.00 mg/dl in men and/or estimated glomerular filtration rate (GFR) < 30 ml/min/1.73m2), history of dialysis, nephrotic syndrome or renovascular hypertension.
Use of aliskiren should be avoided in patients with severe renal impairment (GFR < 30 mL/min/1.73m2).
As for other agents acting on the renin-angiotensin system, caution should be exercised when aliskiren is given in the presence of conditions pre-disposing to kidney dysfunction such as hypovolaemia (e.g. due to blood loss, severe prolonged diarrhoea, prolonged vomiting etc.), heart disease, liver disease or kidney disease. Acute renal failure, reversible upon discontinuation of treatment, has been reported in at-risk patients receiving aliskiren in post-marketing experience. In the event that any signs of renal failure occur, aliskiren should be promptly discontinued.
No adjustment of the initial dose is required for patients with mild to moderate renal impairment (GFR ≥ 30 mL/min/1.73m2) (see sections 4.4 and 5.2).
Patients with renal artery stenosis
No controlled clinical data are available on the use of Rasilez in patients with unilateral or bilateral renal artery stenosis, or stenosis to a solitary kidney. However, as with other agents acting on the renin-angiotensin system, there is an increased risk of renal insufficiency, including acute renal failure, when patients with renal artery stenosis are treated with aliskiren. Therefore, caution should be exercised in these patients. If renal failure occurs, treatment should be discontinued.

Risk for renal dysfunction/Serum electrolyte changes
As for other agents that act on the RAAS, aliskiren may increase potassium, serum creatinine and blood urea nitrogen. Increases in serum potassium may be exacerbated by the concomitant use of other agents acting on the RAAS or use of non-steroidal anti- inflammatory drugs (NSAIDs). Patients with diabetes mellitus are at increased risk of hyperkalemia during aliskiren therapy.
Worsening of renal function may occur in patients receiving aliskiren and other RAAS agents or NSAIDs concomitantly, or in those with pre-existing renal disease, diabetes mellitus or with other conditions pre-disposing to renal dysfunction such as hypovolemia, heart failure or liver disease.
RAS API JUN15 CL V10                                      REF CDS 6May14 & 18Dec14 Close monitoring of serum electrolytes to detect possible electrolyte (potassium) imbalances is advised at initiation of therapy with Rasilez and periodic monitoring thereafter.


Pediatric patients (less than 18 years of age)
Aliskiren is a P-glycoprotein (P-gp) substrate, and there is a potential for aliskiren overexposure in children with an immature P-gp drug transporter system. The age at which the transporter system is mature cannot be determined (see sections 5 and 5.3).
Therefore, Rasilez is contraindicated in children less than 2 years of age and should not be used in children 2 to less than 6 years of age.
Limited safety data are available from a pharmacokinetic study of aliskiren treatment in 39 hypertensive children 6 to less than 18 years of age (see sections 4.8 and 5).
Use of Rasilez in this age group is not recommended.

Effects on Driving