Rasilez HCT

Posology The recommended dose of Rasilez HCT is one tablet per day. The antihypertensive effect is largely manifested within 1 week and the maximum effect is generally seen within 4 weeks. Posology in patients not adequately controlled with aliskiren or hydrochlorothiazide monotherapy Individual dose titration with each of the two components may be recommended before changing to the fixed combination.

When clinically appropriate, direct change from monotherapy to the fixed combination may be considered. 5 mg alone. 5 mg. 5 mg. 5 mg or Rasilez HCT 150 mg/25 mg. If blood pressure remains uncontrolled after 2-4 weeks of therapy, the dose may be titrated up to a maximum of Rasilez HCT 300 mg/25 mg daily.

Dosing should be individualised and adjusted according to the patient’s clinical response. Posology as substitution therapy For convenience, patients receiving aliskiren and hydrochlorothiazide from separate tablets may be switched to a fixed combination tablet of Rasilez HCT containing the same component doses.

73 m2). 2). Hepatic impairment Rasilez HCT is contraindicated in patients with severe hepatic impairment and should be used with caution in patients with mild to moderate hepatic impairment or progressive liver disease. 2). Elderly people (over 65 years) The recommended starting dose of aliskiren in elderly patients is 150 mg.

No clinically meaningful additional blood pressure reduction is observed by increasing the dose to 300 mg in the majority of elderly patients. Paediatric population The safety and efficacy of Rasilez HCT in children below 18 years have not yet been established.

No data are available. Rasilez HCT is contraindicated in children from birth to less than 2 years. 3). The safety and efficacy of Rasilez HCT in children aged 6 to 17 years have not yet been established. 2. Use of Rasilez HCT is not recommended in this population.

Method of administration Oral use. The tablets should be swallowed whole with some water. Rasilez HCT should be taken once a day, always with or always without food, preferably at the same time each day. Patients should establish a convenient daily schedule of medicinal product intake and maintain a steady temporal relationship with food intake.

5).

Summary of the safety profile The safety of Rasilez HCT has been evaluated in more than 3,900 patients, including over 700 treated for over 6 months, and 190 for over 1 year. The incidence of adverse reactions showed no association with gender, age, body mass index, race or ethnicity.

Treatment with Rasilez HCT had an overall incidence of adverse experiences at doses up to 300 mg/25 mg similar to placebo. The most common adverse reaction observed with Rasilez HCT is diarrhoea. The adverse reactions previously reported with one of the individual components of Rasilez HCT (aliskiren and hydrochlorothiazide) and included in the tabulated list of adverse reactions may occur with Rasilez HCT.

Tabulated list of adverse reactions The frequency of adverse reactions listed below is defined 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).

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. The adverse reactions observed with Rasilez HCT or with monotherapy with one or both of the two components are included in the table below.

For adverse reactions observed with more than one component of a fixed-dose combination, the highest frequency is listed in the table below. Neoplasms benign, malignant and unspecified (incl cysts and polyps) Not known Non-melanoma skin cancer (Basal cell carcinoma and Squamous cell carcinoma) Blood and lymphatic system disorders Rare Thrombocytopenia sometimes with purpurah Very rare Agranulocytosish, bone marrow depressionh, haemolytic anaemiah, leucopeniah Not known Aplastic anaemiah Immune system disorders Rare Anaphylactic reactionsa, hypersensitivity reactionsa,h Metabolism and nutrition disorders Very common Hypokalaemiah Common Hyperuricaemiah, hypomagnesaemiah Rare Hypercalcaemiah, hyperglycaemiah, worsening of diabetic metabolic stateh Very rare Hypochloraemic alkalosish Psychiatric disorders Rare Depressionh, sleep disturbancesh Nervous system disorders Rare Headacheh, paraesthesiah Eye disorders Rare Visual impairmenth Not known Acute angle-closure glaucomah, choroidal effusionh Ear and labyrinth disorders Not known Vertigoa Cardiac disorders Common Dizzinessa,h Uncommon Palpitationsa, oedema peripherala Rare Cardiac arrhythmiashMedicinal Product no longer authorised 15 Vascular disorders Common Orthostatic hypotensionh Uncommon Hypotensionc,a Respiratory, thoracic and mediastinal disorders Uncommon Cougha Very rare Respiratory distress (including pneumonitis and pulmonary oedema) h Not known Dyspnoeaa Gastrointestinal disorders Common Diarrhoeac,a,h, decreased appetiteh, nausea and vomitinga,h Rare Abdominal discomforth, constipationh Very rare Pancreatitish Hepatobiliary disorders Rare Intrahepatic cholestasish, jaundicea,h Not known Liver disordera,*, hepatitisa, liver failurea,** Skin and subcutaneous tissue disorders Common Urticaria and other forms of rasha,h Uncommon Severe cutaneous adverse reactions (SCARs) including Stevens Johnson syndromea, toxic epidermal necrolysis (TEN)a, oral mucosal reactionsa, pruritusa Rare Angioedemaa, erythemaa, photosensitivity reactionsh Very rare Cutaneous lupus erythematosus-like reactionsh, reactivation of cutaneous lupus erythematosush, vasculitis necrotising and toxic epidermal necrolysish Not known Erythema multiformeh Musculoskeletal and connective tissue disorders Common Arthralgiaa Not known Muscle spasmh Renal and urinary disorders Uncommon Acute renal failurea,h, renal impairmenta Not known Renal dysfunctionh Reproductive system and breast disorders Common Impotenceh General disorders and administration site conditions Not known Astheniah, pyrexiah Investigations Very common Increases in cholesterol and triglyceridesh Common Hyperkalaemiaa, hyponatraemia c, a, h Uncommon Liver enzyme increaseda Rare Haemoglobin decreaseda, haematocrit decreaseda, blood creatinine increaseda, glycosuriah c Adverse reaction observed with Rasilez HCT a Adverse reaction observed with monotherapy with aliskiren h Adverse reaction observed with monotherapy with hydrochlorothiazide * Isolated cases of liver disorder with clinical symptoms and laboratory evidence of more marked hepatic dysfunction.

Non-melanoma skin cancer An increased risk of non-melanoma skin cancer (NMSC) [basal cell carcinoma (BCC) and squamous cell carcinoma (SCC)] with increasing cumulative dose of hydrochlorothiazide (HCTZ) exposure has been observed in two epidemiological studies based on the Danish National Cancer Registry.

Photosensitizing actions of HCTZ could act as a possible mechanism for NMSC. Patients taking HCTZ should be informed of the risk of NMSC and advised to regularly check their skin for any new lesions and promptly report any suspicious skin lesions.

Possible preventive measures such as limited exposure to sunlight and UV rays and, in case of exposure, adequateMedicinal Product no longer authorised 5 protection should be advised to the patients in order to minimize the risk of skin cancer.

Suspicious skin lesions should be promptly examined potentially including histological examinations of biopsies. 8). 8). 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.

1). Rasilez HCT should be used with caution in patients with heart failure due to limited clinical efficacy and safety data. 5). 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 HCT, or the treatment should start under close medical supervision. Electrolyte imbalance Treatment with Rasilez HCT should only start after correction of hypokalaemia and any coexisting hypomagnesaemia.

Thiazide diuretics can precipitate new onset hypokalaemia or exacerbate pre- existing hypokalaemia. Thiazide diuretics should be administered with caution in patients with conditions involving enhanced potassium loss, for example salt-losing nephropathies and prerenal (cardiogenic) impairment of kidney function.

1, or to other sulfonamide-derived substances. − History of angioedema with aliskiren. − Hereditary or idiopathic angioedema. 6). − Anuria. 73 m2). − Hyponatraemia, hypercalcaemia, symptomatic hyperuricaemia and refractory hypokalaemia. − Severe hepatic impairment.

g. 5). 1). 3).