Rasilez · 4.4 Special warnings and precautions for use · 1

HOS-154184 · has-adverse-reaction-information · PDF-Seite 8

Summary of the safety profile Serious adverse reactions include anaphylactic reaction and angioedema which have been reported in post-marketing experience and may occur rarely (less than 1 case per 1,000 patients). The most common adverse reaction is diarrhoea. Tabulated list of adverse reactions Aliskiren has been evaluated for safety in more than 7,800 patients, including over 2,300 treated for over 6 months, and more than 1,200 for over 1 year. The adverse reactions are ranked under heading of frequency, the most frequent first, using the following convention: 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) and not known (cannot be estimated from the available data). 8 Table 1 Immune system disorders Rare: Anaphylactic reactions, hypersensitivity reactions Nervous system disorders Common: Dizziness Ear and labyrinth disorders Not known: Vertigo Cardiac disorders Uncommon: Palpitations, oedema peripheral Vascular disorders Uncommon: Hypotension Respiratory, thoracic and mediastinal disorders Uncommon: Cough Not known: Dyspnoea Gastrointestinal disorders Common: Diarrhoea Not known: Nausea, vomiting Hepatobiliary disorders Not known: Liver disorder*, jaundice, hepatitis, liver failure** Skin and subcutaneous tissue disorders Uncommon: Severe cutaneous adverse reactions (SCARs) including Stevens Johnson syndrome, toxic epidermal necrolysis (TEN) and oral mucosal reactions, rash, pruritus, urticaria Rare: Angioedema, erythema Musculoskeletal and connective tissue disorders Common: Arthralgia Renal and urinary disorders Uncommon: Acute renal failure, renal impairment Investigations Common: Hyperkalaemia Uncommon: Liver enzyme increased Rare: Haemoglobin decreased, haematocrit decreased, blood creatinine increased Not known: Hyponatraemia *Isolated cases of liver disorder with clinical symptoms and laboratory ev

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HOS-154180 · has-contraindication-information · PDF-Seite 3

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. - History of angioedema with aliskiren. - Hereditary or idiopathic angioedema. - Second and third trimesters of pregnancy (see section 4.6). - The concomitant use of aliskiren with ciclosporin and itraconazole, two highly potent P-glycoprotein (P-gp) inhibitors, and other potent P-gp inhibitors (e.g. quinidine), is contraindicated (see section 4.5). - The concomitant use of Rasilez with an angiotensin converting enzyme inhibitor(ACEI) or an angiotensin II receptor blocker (ARB) is contraindicated in patients with diabetes mellitus or renal impairment (GFR < 60 ml/min/1.73 m2) (see sections 4.5 and 5.1). - Children from birth to less than 2 years (see sections 4.2 and 5.3).

HOS-154179 · has-indication-information · PDF-Seite 2

Treatment of essential hypertension in adults.

HOS-154182 · has-interaction-information · PDF-Seite 5

Contraindicated (see section 4.3) P-gp potent inhibitors A single dose interaction study in healthy subjects has shown that ciclosporin (200 and 600 mg) increases Cmax of aliskiren 75 mg approximately 2.5-fold and AUC approximately 5-fold. The increase may be higher with higher aliskiren doses. In healthy subjects, itraconazole (100 mg) increases AUC and Cmax of aliskiren (150 mg) by 6.5-fold and 5.8-fold, respectively. Therefore, concomitant use of aliskiren and P-gp potent inhibitors is contraindicated (see section 4.3). Not recommended Fruit juice and drinks containing plant extracts Administration of fruit juice with aliskiren resulted in a decrease in AUC and Cmax of aliskiren. Co-administration of grapefruit juice with aliskiren 150 mg resulted in a 61% decrease in aliskiren AUC and co-administration with aliskiren 300 mg resulted in a 38% decrease in aliskiren AUC. Co-administration of orange or apple juice with aliskiren 150 mg resulted in a 62% decrease in aliskiren AUC or in a 63% decrease in aliskiren AUC, respectively. This decrease is likely due to an inhibition of organic anion transporting polypeptide-mediated uptake of aliskiren by components of fruit juice in the gastrointestinal tract. Therefore, because of the risk of therapeutic failure, fruit juice should not be taken together with aliskiren. The effect of drinks containing plant extracts (including herbal teas) on the absorption of aliskiren has not been investigated. However, compounds potentially 5 inhibiting organic anion transporting polypeptide-mediated uptake of aliskiren are widely present in fruits, vegetables, and many other plant products. Therefore, drinks containing plant extracts, including herbal teas, should not be taken together with aliskiren (see section 4.2) Dual blockade of the RAAS with aliskiren, ARBs or ACEIs Clinical trial data has shown that dual blockade of the RAAS through the combined use of ACEIs, ARBs or aliskiren is associated with a higher frequency of adverse events such as hypotension, stroke, hyperkalaemia and decreased renal function (including acute renal failure) compared to the use of a single RAAS-acting agent (see sections 4.3, 4.4 and 5.1). Caution required with concomitant use P-gp interactions MDR1/Mdr1a/1b (P-gp) was found to be the major efflux system involved in intestinal absorption and biliary excretion of aliskiren in preclinical studies (see section 5.2). Rifampicin, which

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HOS-154183 · has-pregnancy-information · PDF-Seite 8

Pregnancy There are no data on the use of aliskiren in pregnant women. Aliskiren was not teratogenic in rats or rabbits (see section 5.3). Other substances that act directly on the RAAS have been associated with serious foetal malformations and neonatal death. As for any medicine that acts directly on the RAAS, alsikiren should not be used during the first trimester of pregnancy or in women planning to become pregnant and is contraindicated during the second and third trimesters (see section 4.3). Healthcare professionals prescribing any agents acting on the RAAS should counsel women of childbearing potential about the potential risk of these agents during pregnancy. If pregnancy is detected during therapy, treatment should be discontinued accordingly. Breast-feeding It is unknown whether aliskiren/metabolites are excreted in human milk. Aliskiren was secreted in the milk of lactating rats. A risk to the newborns/infants cannot be excluded. Aliskiren should not be used during breast-feeding. Fertility There are no clinical data on fertility.

HOS-154181 · has-warning-information · PDF-Seite 3

General In the event of severe and persistent diarrhoea, Rasilez therapy should be stopped (see section 4.8). Aliskiren should be used with caution in patients with serious congestive heart failure (New York Heart Association (NYHA) functional class III-IV) (see section 5.1). Aliskiren should be used with caution in patients with heart failure treated with furosemide or torasemide (see section 4.5). 3 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. Risk of symptomatic hypotension Symptomatic hypotension could occur after initiation of treatment with aliskiren in the following cases: - Patients with marked volume depletion or patients with salt depletion (e.g. those receiving high doses of diuretics) or - Combined use of aliskiren with other agents acting on the RAAS. The volume or salt depletion should be corrected prior to administration of Rasilez, or the treatment should start under close medical supervision. Renal impairment In clinical studies aliskiren 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 GFR < 30 ml/min/1.73 m2), history of dialysis, nephrotic syndrome or renovascular hypertension. It is not recommended in patients with severe renal impairment (GFR < 30 ml/min/1.73 m2). As for other medicinal products 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, diabetes mellitus or kidney disease. Acute renal failure, reversible upon discontinuation of treatment, has been reported in at-risk patients receiving aliskiren in post-marketing exp

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