Riprazo

1 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX I 

 

SUMMARY OF PRODUCT CHARACTERISTICS 

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1. NAME OF THE MEDICINAL PRODUCT 

 

Riprazo 150 mg film-coated tablets 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 

 

Each film-coated tablet contains 150 mg aliskiren (as hemifumarate). 

 

For the full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 

 

Film-coated tablet 

 

Light-pink, biconvex, round tablet, imprinted “IL” on one side and “NVR” on the other side. 

 

 

4. CLINICAL PARTICULARS 

 

4.1 Therapeutic indications 

 

Treatment of essential hypertension in adults. 

 

4.2 Posology and method of administration 

 

Posology 

The recommended dose of Riprazo is 150 mg once daily. In patients whose blood pressure is not 

adequately controlled, the dose may be increased to 300 mg once daily. 

 

The antihypertensive effect is substantially present within two weeks (85-90%) after initiating therapy 

with 150 mg once daily. 

 

Riprazo may be used alone or in combination with other antihypertensive agents with the exception of 

use in combination with angiotensin converting enzyme inhibitors (ACEI) or angiotensin II receptor 

blockers (ARB) in patients with diabetes mellitus or renal impairment (glomerular filtration rate 

(GFR) < 60 ml/min/1.73 m
2
) (see sections 4.3, 4.4 and 5.1). 

 

Special populations 

Renal impairment 

No adjustment of the initial dose is required for patients with mild to moderate renal impairment (see 

sections 4.4 and 5.2). Riprazo is not recommended in patients with severe renal impairment (GFR 

< 30 ml/min/1.73 m
2
). Concomitant use of Riprazo with ARBs or ACEIs is contraindicated in patients 

with renal impairment (GFR < 60 ml/min/1.73 m
2
) (see section 4.3). 

 

Hepatic impairment 

No adjustment of the initial dose is required for patients with mild to severe hepatic impairment (see 

section 5.2). 

 

Elderly patients aged 65 years and over 

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. 

 

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Paediatric population 

The safety and efficacy of Riprazo in children aged below 18 years have not yet been established. No 

data are available. 

 

Method of administration 

Oral use. The tablets should be swallowed whole with some water. Riprazo should be taken with a 

light meal once a day, preferably at the same time each day. Grapefruit juice should not be taken 

together with Riprazo (see section 4.5). 

 

4.3 Contraindications 

 

- 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-gp 

inhibitors, and other potent P-gp inhibitors (e.g. quinidine), is contraindicated (see section 4.5). 

 

- The concomitant use of aliskiren with ARBs or ACEIs is contraindicated in patients with 

diabetes mellitus or renal impairment (GFR < 60 ml/min/1.73 m
2
) (see sections 4.2, 4.4, 4.5 and 

5.1). 

 

4.4 Special warnings and precautions for use 

 

General 

In the event of severe and persistent diarrhoea, Riprazo 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). 

 

Dual blockade of the renin-angiotensin-aldosterone system (RAAS) 

Hypotension, syncope, stroke, hyperkalaemia, and changes in 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 renin-angiotensin-aldosterone system by 

combining aliskiren with an angiotensin converting enzyme inhibitor (ACEI) or an angiotensin II 

receptor blocker (ARB) is therefore not recommended. 

 

The use of aliskiren in combination with ARBs or ACEIs is contraindicated in patients with diabetes 

mellitus or renal impairment (GFR < 60 ml/min/1.73 m
2
) (see section 4.3). 

 

Anaphylactic reactions and angioedema 

Anaphylactic reactions have been observed during treatment with aliskiren from post-marketing 

experience (see section 4.8). As with other medicinal products 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 (angiotensin converting enzyme inhibitors or angiotensin receptor blockers) (see section 4.8). 

 

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In post-marketing experience, angioedema or angioedema-like reactions have been reported when 

aliskiren was co-administered with ACEIs and/or ARBs (see section 4.8). 

 

Special caution is necessary in patients with a hypersensitivity predisposition. 

 

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 the treatment. 

 

If anaphylactic reactions or angioedema occur, Riprazo should be promptly discontinued and 

appropriate therapy and monitoring provided until complete and sustained resolution of signs and 

symptoms has occurred. Patients should be informed to report to the physician any signs suggestive of 

allergic reactions, in particular difficulties in breathing or swallowing, swelling of face, extremities, 

eyes, lips or tongue. Where there is involvement of the tongue, glottis or larynx adrenaline should be 

administered. In addition, measures necessary to maintain patent airways should be provided. 

 

Sodium and/or volume depleted patients 

In patients with marked volume- and/or salt-depletion (e.g. those receiving high doses of diuretics) 

symptomatic hypotension could occur after initiation of treatment with Riprazo. This condition should 

be corrected prior to administration of Riprazo, or the treatment should start under close medical 

supervision. 

 

Renal impairment 

In clinical studies Riprazo 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 m
2
), history of dialysis, nephrotic syndrome or 

renovascular hypertension. Riprazo is not recommended in patients with severe renal impairment 

(GFR < 30 ml/min/1.73 m
2
). 

 

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 (eg. due to blood loss, severe prolonged diarrhoea, prolonged vomiting, etc.), heart 

disease, liver disease, diabetes mellitus or kidney disease. The concomitant use of aliskiren and 

ACEIs or ARBs is contraindicated in patients with renal impairment (GFR < 60 ml/min/1.73 m
2
). 

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. 

 

Increases in serum potassium have been observed with aliskiren in post-marketing experience and 

these may be exacerbated by concomitant use of other agents acting on the RAAS or by non-steroidal 

anti-inflammatory drugs (NSAIDs). Consistent with standard medical practice, periodic determination 

of renal function including serum electrolytes is advised if co-administration is considered necessary. 

 

Renal artery stenosis 

No controlled clinical data are available on the use of Riprazo in patients with unilateral or bilateral 

renal artery stenosis, or stenosis to a solitary kidney. However, as with other medicinal products 

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. 

 

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4.5 Interaction with other medicinal products and other forms of interaction 

 

Contraindicated (see section 4.3) 

Dual RAAS blockade 

The combination of aliskiren with ARBs or ACEIs is contraindicated in patients with diabetes 

mellitus or renal impairment (GFR < 60 ml/min/1.73 m
2
) and is not recommended in other patients 

(see sections 4.3, 4.4 and 5.1). 

 

P-glycoprotein (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 (see section 4.2) 

Grapefruit juice 

Administration of grapefruit juice with aliskiren resulted in a decrease in AUC and Cmax of aliskiren. 

Co-administration 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. This decrease is 

likely due to an inhibition of organic anion transporting polypeptide-mediated uptake of aliskiren by 

grapefruit juice in the gastrointestinal tract. Therefore, because of the risk of therapeutic failure, 

grapefruit juice should not be taken together with Riprazo. 

 

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. Rifampicin, which is an inducer of P-gp, reduced 

aliskiren bioavailability by approximately 50% in a clinical study. Other inducers of P-gp (St. John’s 

wort) might decrease the bioavailability of Riprazo. Although this has not been investigated for 

aliskiren, it is known that P-gp also controls tissue uptake of a variety of substrates and P-gp 

inhibitors can increase the tissue-to-plasma concentration ratios. Therefore, P-gp inhibitors may 

increase tissue levels more than plasma levels. The potential for drug interactions at the P-gp site will 

likely depend on the degree of inhibition of this transporter. 

 

Moderate P-gp inhibitors 

Co-administration of ketoconazole (200 mg) or verapamil (240 mg) with aliskiren (300 mg) resulted 

in a 76% or 97% increase in aliskiren AUC, respectively. The change in plasma levels of aliskiren in 

the presence of ketoconazole or verapamil is expected to be within the range that would be achieved if 

the dose of aliskiren were doubled; aliskiren doses of up to 600 mg, or twice the highest 

recommended therapeutic dose, have been found to be well tolerated in controlled clinical trials. 

Preclinical studies indicate that aliskiren and ketoconazole co-administration enhances aliskiren 

gastrointestinal absorption and decreases biliary excretion. Therefore, caution should be exercised 

when aliskiren is administered with ketoconazole, verapamil or other moderate P-gp inhibitors 

(clarithromycin, telithromycin, erythromycin, amiodarone). 

 

Medicinal products affecting serum potassium levels 

Concomitant use of other agents affecting the RAAS, of NSAIDs or of agents that increase serum 

potassium levels (e.g. potassium-sparing diuretics, potassium supplements, salt substitutes containing 

potassium, heparin) may lead to increases in serum potassium. If co-medication with an agent 

affecting the level of serum potassium is considered necessary, caution is advisable. The combination 

of aliskiren with ARBs or ACEIs is contraindicated in patients with diabetes mellitus or renal 

impairment (GFR < 60 ml/min/1.73 m
2
) and is not recommended in other patients (see sections 4.3, 

4.4 and 5.1). 

 

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Non-steroidal anti-inflammatory drugs (NSAIDs) 

As with other agents acting on the renin-angiotensin system, NSAIDs may reduce the anti-

hypertensive effect of aliskiren. In some patients with compromised renal function (dehydrated 

patients or elderly patients) aliskiren given concomitantly with NSAIDs may result in further 

deterioration of renal function, including possible acute renal failure, which is usually reversible. 

Therefore the combination of aliskiren with an NSAID requires caution, especially in elderly patients. 

 

Furosemide 

When aliskiren was co-administered with furosemide, the AUC and Cmax of furosemide were reduced 

by 28% and 49%, respectively. It is therefore recommended that the effects be monitored when 

initiating and adjusting furosemide therapy to avoid possible under-utilisation in clinical situations of 

volume overload. 

 

Warfarin 

The effects of Riprazo on warfarin pharmacokinetics have not been evaluated. 

 

Food interactions 

Meals (low or high fat content) have been shown to reduce the absorption of Riprazo substantially 

(see section 4.2). 

 

No interactions 

- Compounds that have been investigated in clinical pharmacokinetic studies include 

acenocoumarol, atenolol, celecoxib, pioglitazone, allopurinol, isosorbide-5-mononitrate and 

hydrochlorothiazide. No interactions have been identified. 

 

- Co-administration of aliskiren with either metformin (↓28%), amlodipine (↑29%) or cimetidine 

(↑19%) resulted in between 20% and 30% change in Cmax or AUC of Riprazo. When 

administered with atorvastatin, steady-state Riprazo AUC and Cmax increased by 50%. Co-

administration of Riprazo had no significant impact on atorvastatin, metformin or amlodipine 

pharmacokinetics. As a result no dose adjustment for Riprazo or these co-administered 

medicinal products is necessary. 

 

- Digoxin and verapamil bioavailability may be slightly decreased by Riprazo. 

 

- CYP450 interactions 

Aliskiren does not inhibit the CYP450 isoenzymes (CYP1A2, 2C8, 2C9, 2C19, 2D6, 2E1 and 3A). 

Aliskiren does not induce CYP3A4. Therefore aliskiren is not expected to affect the systemic 

exposure of substances that inhibit, induce or are metabolised by these enzymes. Aliskiren is 

metabolised minimally by the cytochrome P450 enzymes. Hence, interactions due to inhibition or 

induction of CYP450 isoenzymes are not expected. However, CYP3A4 inhibitors often also affect P-

gp. Increased aliskiren exposure during co-administration of CYP3A4 inhibitors that also inhibit P-gp 

can therefore be expected (see other P-gp references in section 4.5). 

 

- P-gp substrates or weak inhibitors 

No relevant interactions with atenolol, digoxin, amlodipine or cimetidine have been observed. When 

administered with atorvastatin (80 mg), steady-state aliskiren (300 mg) AUC and Cmax increased by 

50%. In experimental animals, it has been shown that P-gp is a major determinant of Riprazo 

bioavailability. Inducers of P-gp (St. John’s wort, rifampicin) might therefore decrease the 

bioavailability of Riprazo. 

 

- Organic anion transporting polypeptide (OATP) inhibitors 

Preclinical studies indicate that aliskiren might be a substrate of organic anion transporting 

polypeptides. Therefore, the potential exists for interactions between OATP inhibitors and aliskiren 

when administered concomitantly (see interaction with Grapefruit juice). 

 

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4.6 Fertility, pregnancy and lactation 

 

Pregnancy 

There are no data on the use of aliskiren in pregnant women. Riprazo 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, 

Riprazo 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, Riprazo should be discontinued accordingly. 

 

Breast-feeding 

It is not known whether aliskiren is excreted in human milk. Riprazo was secreted in the milk of 

lactating rats. Its use is therefore not recommended in women who are breast-feeding. 

 

Fertility 

There are no clinical data on fertility. 

 

4.7 Effects on ability to drive and use machines 

 

Riprazo has negligible influence on the ability to drive and use machines. However, when driving 

vehicles or operating machinery it must be borne in mind that dizziness or weariness may occasionally 

occur when taking Riprazo. 

 

4.8 Undesirable effects 

 

Summary of the safety profile 

Riprazo 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 incidence of adverse reactions showed no 

association with gender, age, body mass index, race or ethnicity. 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. 

 

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Tabulated list of adverse reactions: 

The adverse drug reactions (Table 1) 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). Within each frequency grouping, undesirable effects are presented 

in order of decreasing seriousness. 

 

Table 1 

 

Immune system disorders 

 Rare: Anaphylactic reactions, hypersensitivity reactions 

Nervous system disorders 

 Common: Dizziness 

Cardiac disorders 

 Uncommon: Palpitations 

Vascular disorders 

 Uncommon: Hypotension 

Respiratory, thoracic and mediastinal disorders 

 Uncommon: Cough 

Gastrointestinal disorders 

 Common: Diarrhoea 

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 

General disorders and administration site conditions 

 Uncommon: Oedema peripheral 

Investigations 

 Common: Hyperkalaemia 

 Uncommon: Liver enzyme increased 

 Rare: Haemoglobin decreased, haematocrit decreased, blood creatinine 

increased 

 

Description of selected adverse reactions 

Hypersensitivity reactions including anaphylactic reactions and angioedema have occurred during 

treatment with aliskiren. 

 

In controlled clinical trials, angioedema and hypersensitivity reactions occurred rarely during 

treatment with aliskiren with rates comparable to treatment with placebo or comparators. 

 

Cases of angioedema or symptoms suggestive of angioedema (swelling of the face, lips, throat and/or 

tongue) have also been reported in post-marketing experience. A number of these patients had a 

history of angioedema or symptoms suggestive of angioedema which in some cases was associated 

with the administration of other medicines known to cause angioedema, including RAAS blockers 

(ACEIs or ARBs). 

 

In post-marketing experience, cases of angioedema or angioedema-like reactions have been reported 

when aliskiren was co-administered with ACEIs and/or ARBs. 

 

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Hypersensitivity reactions including anaphylactic reactions have also been reported in post-marketing 

experience (see section 4.4). 

 

In the event of any signs suggesting a hypersensitivity reaction/angioedema (in particular difficulties 

in breathing or swallowing, rash, itching, hives or swelling of the face, extremities, eyes, lips and/or 

tongue, dizziness) patients should discontinue treatment and contact the physician (see section 4.4). 

 

Arthralgia has been reported in post-marketing experience. In some cases this occurred as part of a 

hypersensitivity reaction. 

 

In post-marketing experience, renal dysfunction and cases of acute renal failure have been reported in 

patients at risk (see section 4.4). 

 

Laboratory findings 

In controlled clinical trials, clinically relevant changes in standard laboratory parameters were 

uncommonly associated with the administration of Riprazo. In clinical studies in hypertensive 

patients, Riprazo had no clinically important effects on total cholesterol, high density lipoprotein 

cholesterol (HDL-C), fasting triglycerides, fasting glucose or uric acid. 

 

Haemoglobin and haematocrit: Small decreases in haemoglobin and haematocrit (mean decreases of 

approximately 0.05 mmol/l and 0.16 volume percent, respectively) were observed. No patients 

discontinued therapy due to anaemia. This effect is also seen with other agents acting on the renin-

angiotensin system, such as ACEIs and ARBs. 

 

Serum potassium: Increases in serum potassium have been observed with aliskiren and these may be 

exacerbated by concomitant use of other agents acting on the RAAS or by NSAIDs. Consistent with 

standard medical practice, periodic determination of renal function including serum electrolytes is 

advised if co-administration is considered necessary. The combination of aliskiren with ARBs or 

ACEIs is contraindicated in patients with diabetes mellitus or renal impairment (GFR 

< 60 ml/min/1.73 m
2
) and is not recommended in other patients (see sections 4.3, 4.4 and 5.1). 

 

4.9 Overdose 

 

Symptoms 

Limited data are available related to overdose in humans. The most likely manifestations of 

overdosage would be hypotension, related to the antihypertensive effect of aliskiren. 

 

Treatment 

If symptomatic hypotension should occur, supportive treatment should be initiated. 

 

In a study conducted in patients with end stage renal disease (ESRD) receiving haemodialysis, 

dialysis clearance of aliskiren was low (< 2% of oral clearance). Therefore dialysis is not adequate to 

treat aliskiren over-exposure. 

 

 

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5. PHARMACOLOGICAL PROPERTIES 

 

5.1 Pharmacodynamic properties 

 

Pharmacotherapeutic group: Agents acting on the renin-angiotensin system; renin inhibitor, ATC 

code: C09XA02 

 

Aliskiren is an orally active, non-peptide, potent and selective direct inhibitor of human renin. 

 

By inhibiting the enzyme renin, aliskiren inhibits the RAAS at the point of activation, blocking the 

conversion of angiotensinogen to angiotensin I and decreasing levels of angiotensin I and angiotensin 

II. Whereas other agents that inhibit the RAAS (ACEI and angiotensin II receptor blockers (ARB)) 

cause a compensatory rise in plasma renin activity (PRA), treatment with aliskiren decreases PRA in 

hypertensive patients by approximately 50 to 80%. Similar reductions were found when aliskiren was 

combined with other antihypertensive agents. The clinical implications of the differences in effect on 

PRA are not known at the present time. 

 

Hypertension 

In hypertensive patients, once-daily administration of Riprazo at doses of 150 mg and 300 mg 

provided dose-dependent reductions in both systolic and diastolic blood pressure that were maintained 

over the entire 24-hour dose interval (maintaining benefit in the early morning) with a mean peak to 

trough ratio for diastolic response of up to 98% for the 300 mg dose. 85 to 90% of the maximal blood-

pressure-lowering effect was observed after 2 weeks. The blood-pressure-lowering effect was 

sustained during long-term treatment, and was independent of age, gender, body mass index and 

ethnicity. Riprazo has been studied in 1,864 patients aged 65 years or older, and in 426 patients aged 

75 years or older. 

 

Riprazo monotherapy studies have shown blood pressure lowering effects comparable to other classes 

of antihypertensive agents including ACEI and ARB. Compared to a diuretic (hydrochlorothiazide - 

HCTZ), Riprazo 300 mg lowered systolic/diastolic blood pressure by 17.0/12.3 mmHg, compared to 

14.4/10.5 mmHg for HCTZ 25 mg after 12 weeks of treatment. 

 

Combination therapy studies are available for Riprazo added to the diuretic hydrochlorothiazide, the 

calcium channel blocker amlodipine and the beta blocker atenolol. These combinations were well 

tolerated. Riprazo induced an additive blood-pressure-lowering effect when added to 

hydrochlorothiazide. In patients who did not adequately respond to 5 mg of the calcium channel 

blocker amlodipine, the addition of Riprazo 150 mg had a blood-pressure-lowering effect similar to 

that obtained by increasing amlodipine dose to 10 mg, but had a lower incidence of oedema (aliskiren 

150 mg/amlodipine 5 mg 2.1% vs. amlodipine 10 mg 11.2%). 

 

The efficacy and safety of aliskiren-based therapy were compared to ramipril-based therapy in a 9-

month non-inferiority study in 901 elderly patients (≥ 65 years) with essential systolic hypertension. 

Aliskiren 150 mg or 300 mg per day or ramipril 5 mg or 10 mg per day were administered for 

36 weeks with optional add-on therapy of hydrochlorothiazide (12.5 mg or 25 mg) at week 12, and 

amlodipine (5 mg or 10 mg) at week 22. Over the 12 week period, aliskiren monotherapy lowered 

systolic/diastolic blood pressure by 14.0/5.1 mmHg, compared to 11.6/3.6 mmHg for ramipril, 

consistent with aliskiren being non-inferior to ramipril at the dosages chosen and the differences in 

systolic and diastolic blood pressure were statistically significant. Tolerability was comparable in 

both treatment arms, however cough was more often reported with the ramipril regimen than the 

aliskiren regimen (14.2% vs. 4.4%), whilst diarrhoea was more common with the aliskiren regimen 

than for the ramipril regimen (6.6% vs. 5.0%). 

 

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In a 8-week study in 754 hypertensive elderly (≥ 65 years) and very elderly patients (30% ≥ 75 years) 

aliskiren at doses of 75 mg, 150 mg and 300 mg provided statistically significant superior reduction in 

blood pressure (both systolic and diastolic) when compared to placebo. No additional blood pressure 

lowering effect was detected with 300 mg aliskiren compared to 150 mg aliskiren. All three doses 

were well tolerated in both elderly and very elderly patients. 

 

In obese hypertensive patients who did not adequately respond to HCTZ 25 mg, add-on treatment with 

Riprazo 300 mg provided additional blood pressure reduction that was comparable to add-on 

treatment with irbesartan 300 mg or amlodipine 10 mg. 

 

There has been no evidence of first-dose hypotension and no effect on pulse rate in patients treated in 

controlled clinical studies. Excessive hypotension was uncommonly (0.1%) seen in patients with 

uncomplicated hypertension treated with Riprazo alone. Hypotension was also uncommon (<1%) 

during combination therapy with other antihypertensive agents. With cessation of treatment, blood 

pressure gradually returned towards baseline levels over a period of several weeks, with no evidence 

of a rebound effect for blood pressure or PRA. 

 

In a 36-week study involving 820 patients with ischaemic left ventricular dysfunction, no changes in 

ventricular remodelling as assessed by left ventricular end systolic volume were detected with 

aliskiren compared to placebo on top of background therapy. 

 

The combined rates of cardiovascular death, hospitalisation for heart failure, recurrent heart attack, 

stroke and resuscitated sudden death were similar in the aliskiren group and the placebo group. 

However, in patients receiving aliskiren there was a significantly higher rate of hyperkalaemia, 

hypotension and kidney dysfunction when compared to the placebo group. 

 

Aliskiren was evaluated for cardiovascular and/or renal benefit in a double-blind placebo controlled 

randomised trial in 8,606 patients with type 2 diabetes and chronic kidney disease (evidenced by 

proteinuria and/or GFR < 60 ml/min/1.73 m
2
) with or without cardiovascular disease. In most patients 

arterial blood pressure was well controlled at baseline. The primary endpoint was a composite of 

cardiovascular and renal complications. 

 

In this study, aliskiren 300 mg was compared to placebo when added to standard of care which 

included either an angiotensin converting enzyme inhibitor or an angiotensin receptor blocker. The 

study was discontinued prematurely because the participants were unlikely to benefit from aliskiren. 

Preliminary study results indicated a hazard ratio for the primary endpoint of 1.09 in favour of 

placebo (95% Confidence Interval: 0.97, 1.22, 2-sided p=0.17). In addition, an increased incidence of 

serious adverse outcomes was observed with aliskiren compared to placebo for renal complications 

(4.7% versus 3.3%), hyperkalaemia (36.9% versus 27.1%), hypotension (18.4% versus 14.6%) and 

stroke (2.7% versus 2.0%). The increased incidence of non-fatal stroke was greater in patients with 

renal insufficiency. 

 

Beneficial effects of Riprazo on mortality and cardiovascular morbidity and target organ damage are 

currently unknown. 

 

Cardiac electrophysiology 

No effect on QT interval was reported in a randomised, double-blind, placebo, and active-controlled 

study using standard and Holter electrocardiography. 

 

Paediatric population 

The European Medicines Agency has deferred the obligation to submit the results of studies with 

Riprazo in one or more subsets of the paediatric population in hypertension (see section 4.2 for 

information on paediatric use). 

 

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5.2 Pharmacokinetic properties 

 

Absorption 

Following oral absorption, peak plasma concentrations of aliskiren are reached after 1-3 hours. The 

absolute bioavailability of aliskiren is approximately 2-3%. Meals with a high fat content reduce Cmax 

by 85% and AUC by 70%. At steady state meals with low fat content reduce Cmax by 76% and AUC0-

tau by 67% in hypertensive patients. Steady-state-plasma concentrations are reached within 5-7 days 

following once-daily administration and steady-state levels are approximately 2-fold greater than with 

the initial dose. 

 

Distribution 

Following intravenous administration, the mean volume of distribution at steady state is 

approximately 135 litres, indicating that aliskiren distributes extensively into the extravascular space. 

Aliskiren plasma protein binding is moderate (47-51%) and independent of the concentration. 

 

Biotransformation and elimination 

The mean half-life is about 40 hours (range 34-41 hours). Aliskiren is mainly eliminated as unchanged 

compound in the faeces (78%). Approximately 1.4% of the total oral dose is metabolised. The enzyme 

responsible for this metabolism is CYP3A4. Approximately 0.6% of the dose is recovered in urine 

following oral administration. Following intravenous administration, the mean plasma clearance is 

approximately 9 l/h. 

 

Linearity 

Exposure to aliskiren increased more than in proportion to the increase in dose. After single dose 

administration in the dose range of 75 to 600 mg, a 2-fold increase in dose results in a ~2.3 and 2.6-

fold increase in AUC and Cmax, respectively. At steady state the non-linearity may be more 

pronounced. Mechanisms responsible for deviation from linearity have not been identified. A possible 

mechanism is saturation of transporters at the absorption site or at the hepatobiliary clearance route. 

 

Characteristics in patients 

Aliskiren is an effective once-a-day antihypertensive treatment in adult patients, regardless of gender, 

age, body mass index and ethnicity. 

 

The AUC is 50% higher in elderly (>65 years) than in young subjects. Gender, weight and ethnicity 

have no clinically relevant influence on aliskiren pharmacokinetics. 

 

The pharmacokinetics of aliskiren were evaluated in patients with varying degrees of renal 

insufficiency. Relative AUC and Cmax of aliskiren in subjects with renal impairment ranged between 

0.8 to 2 times the levels in healthy subjects following single dose administration and at steady state. 

These observed changes, however, did not correlate with the severity of renal impairment. No 

adjustment of the initial dosage of Riprazo is required in patients with mild to moderate renal 

impairment (see sections 4.2 and 4.4). Riprazo is not recommended in patients with severe renal 

impairment (glomerular filtration rate (GFR) < 30 ml/min/1.73 m
2
). Concomitant use of Riprazo with 

ARBs or ACEIs is contraindicated in patients with renal impairment (GFR < 60 ml/min/1.73 m
2
) (see 

section 4.3). 

 

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The pharmacokinetics of aliskiren were evaluated in patients with end stage renal disease receiving 

haemodialysis. Administration of a single oral dose of 300 mg aliskiren was associated with very 

minor changes in the pharmacokinetics of aliskiren (change in Cmax of less than 1.2 fold; increase in 

AUC of up to 1.6 fold) compared to matched healthy subjects. Timing of haemodialysis did not 

significantly alter the pharmacokinetics of aliskiren in ESRD patients. Therefore, if administration of 

aliskiren in ESRD patients receiving haemodialysis is considered necessary, no dose adjustment is 

warranted in these patients. However, the use of aliskiren is not recommended in patients with severe 

renal impairment (see section 4.4). 

 

The pharmacokinetics of aliskiren were not significantly affected in patients with mild to severe liver 

disease. Consequently, no adjustment of the initial dose of aliskiren is required in patients with mild 

to severe hepatic impairment. 

 

5.3 Preclinical safety data 

 

Carcinogenic potential was assessed in a 2-year rat study and a 6-month transgenic mouse study. No 

carcinogenic potential was detected. One colonic adenoma and one caecal adenocarcinoma recorded 

in rats at the dose of 1,500 mg/kg/day were not statistically significant. Although aliskiren has known 

irritation potential, safety margins obtained in humans at the dose of 300 mg during a study in healthy 

volunteers were considered to be appropriate at 9-11-fold based on faecal concentrations or 6-fold 

based on mucosa concentrations in comparison with 250 mg/kg/day in the rat carcinogenicity study. 

 

Aliskiren was devoid of any mutagenic potential in the in vitro and in vivo mutagenicity studies. The 

assays included in vitro assays in bacterial and mammalian cells and in vivo assessments in rats. 

 

Reproductive toxicity studies with aliskiren did not reveal any evidence of embryofoetal toxicity or 

teratogenicity at doses up to 600 mg/kg/day in rats or 100 mg/kg/day in rabbits. Fertility, pre-natal 

development and post-natal development were unaffected in rats at doses up to 250 mg/kg/day. The 

doses in rats and rabbits provided systemic exposures of 1 to 4 and 5 times higher, respectively, than 

the maximum recommended human dose (300 mg). 

 
Safety pharmacology studies did not reveal any adverse effects on central nervous, respiratory or 

cardiovascular function. Findings during repeat-dose toxicity studies in animals were consistent with 

the known local irritation potential or the expected pharmacological effects of aliskiren. 

 

 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 

 

Crospovidone 

Magnesium stearate 

Cellulose, microcrystalline 

Povidone 

Silica, colloidal anhydrous 

Hypromellose 

Macrogol 

Talc 

Iron oxide, black (E 172) 

Iron oxide, red (E 172) 

Titanium dioxide (E 171) 

 

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6.2 Incompatibilities 

 

Not applicable 

 

6.3 Shelf life 

 

2 years 

 

6.4 Special precautions for storage 

 

Do not store above 30C. Store in the original package in order to protect from moisture. 

 

6.5 Nature and contents of container 

 

PA/Alu/PVC – Alu blisters: 

Packs containing 7, 14, 28, 30, 50, 56, 84, 90, 98 or 280 tablets. 

Packs containing 84 (3x28), 98 (2x49) or 280 (20x14) tablets are multi-packs. 

 

PVC/polychlorotrifluoroethylene (PCTFE) – Alu blisters: 

Packs containing 14, 28, 30, 50, 56, 90, 98 or 280 tablets. 

Packs containing 98 (2x49) or 280 (20x14) tablets are multi-packs. 

Packs containing 56 and 98 (2x49) tablets are perforated unit-dose blisters. 

 

Not all pack sizes may be marketed. 

 

6.6 Special precautions for disposal 

 

Any unused medicinal product or waste material should be disposed of in accordance with local 

requirements. 

 

 

7. MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Wimblehurst Road 

Horsham 

West Sussex, RH12 5AB 

United Kingdom 

 

 

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8. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/07/409/001-010 

EU/1/07/409/021-030 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 

 

Date of first authorisation: 22 August 2007 

Date of latest renewal: 

 

 

10. DATE OF REVISION OF THE TEXT 

 

 

Detailed information on this medicinal product is available on the website of the European Medicines 

Agency http://www.ema.europa.eu 

 

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1. NAME OF THE MEDICINAL PRODUCT 

 

Riprazo 300 mg film-coated tablets 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 

 

Each film-coated tablet contains 300 mg aliskiren (as hemifumarate). 

 

For the full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 

 

Film-coated tablet 

 

Light-red, biconvex, ovaloid tablet, imprinted “IU” on one side and “NVR” on the other side. 

 

 

4. CLINICAL PARTICULARS 

 

4.1 Therapeutic indications 

 

Treatment of essential hypertension in adults. 

 

4.2 Posology and method of administration 

 

Posology 

The recommended dose of Riprazo is 150 mg once daily. In patients whose blood pressure is not 

adequately controlled, the dose may be increased to 300 mg once daily. 

 

The antihypertensive effect is substantially present within two weeks (85-90%) after initiating therapy 

with 150 mg once daily. 

 

Riprazo may be used alone or in combination with other antihypertensive agents with the exception of 

use in combination with angiotensin converting enzyme inhibitors (ACEI) or angiotensin II receptor 

blockers (ARB) in patients with diabetes mellitus or renal impairment (glomerular filtration rate 

(GFR) < 60 ml/min/1.73 m
2
) (see sections 4.3, 4.4 and 5.1). 

 

Special populations 

Renal impairment 

No adjustment of the initial dose is required for patients with mild to moderate renal impairment (see 

sections 4.4 and 5.2). Riprazo is not recommended in patients with severe renal impairment (GFR 

< 30 ml/min/1.73 m
2
). Concomitant use of Riprazo with ARBs or ACEIs is contraindicated in patients 

with renal impairment (GFR < 60 ml/min/1.73 m
2
) (see section 4.3). 

 

Hepatic impairment 

No adjustment of the initial dose is required for patients with mild to severe hepatic impairment (see 

section 5.2). 

 

Elderly patients aged 65 years and over 

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. 

 

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Paediatric population 

The safety and efficacy of Riprazo in children aged below 18 years have not yet been established. No 

data are available. 

 

Method of administration 

Oral use. The tablets should be swallowed whole with some water. Riprazo should be taken with a 

light meal once a day, preferably at the same time each day. Grapefruit juice should not be taken 

together with Riprazo (see section 4.5). 

 

4.3 Contraindications 

 

- 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-gp 

inhibitors, and other potent P-gp inhibitors (e.g. quinidine), is contraindicated (see section 4.5). 

 

- The concomitant use of aliskiren with ARBs or ACEIs is contraindicated in patients with 

diabetes mellitus or renal impairment (GFR < 60 ml/min/1.73 m
2
) (see sections 4.2, 4.4, 4.5 and 

5.1). 

 

4.4 Special warnings and precautions for use 

 

General 

In the event of severe and persistent diarrhoea, Riprazo 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). 

 

Dual blockade of the renin-angiotensin-aldosterone system (RAAS) 

Hypotension, syncope, stroke, hyperkalaemia, and changes in 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 renin-angiotensin-aldosterone system by 

combining aliskiren with an angiotensin converting enzyme inhibitor (ACEI) or an angiotensin II 

receptor blocker (ARB) is therefore not recommended. 

 

The use of aliskiren in combination with ARBs or ACEIs is contraindicated in patients with diabetes 

mellitus or renal impairment (GFR < 60 ml/min/1.73 m
2
) (see section 4.3). 

 

Anaphylactic reactions and angioedema 

Anaphylactic reactions have been observed during treatment with aliskiren from post-marketing 

experience (see section 4.8). As with other medicinal products 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 (angiotensin converting enzyme inhibitors or angiotensin receptor blockers) (see section 4.8). 

 

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In post-marketing experience, angioedema or angioedema-like reactions have been reported when 

aliskiren was co-administered with ACEIs and/or ARBs (see section 4.8). 

 

Special caution is necessary in patients with a hypersensitivity predisposition. 

 

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 the treatment. 

 

If anaphylactic reactions or angioedema occur, Riprazo should be promptly discontinued and 

appropriate therapy and monitoring provided until complete and sustained resolution of signs and 

symptoms has occurred. Patients should be informed to report to the physician any signs suggestive of 

allergic reactions, in particular difficulties in breathing or swallowing, swelling of face, extremities, 

eyes, lips or tongue. Where there is involvement of the tongue, glottis or larynx adrenaline should be 

administered. In addition, measures necessary to maintain patent airways should be provided. 

 

Sodium and/or volume depleted patients 

In patients with marked volume- and/or salt-depletion (e.g. those receiving high doses of diuretics) 

symptomatic hypotension could occur after initiation of treatment with Riprazo. This condition should 

be corrected prior to administration of Riprazo, or the treatment should start under close medical 

supervision. 

 

Renal impairment 

In clinical studies Riprazo 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 m
2
), history of dialysis, nephrotic syndrome or 

renovascular hypertension. Riprazo is not recommended in patients with severe renal impairment 

(GFR < 30 ml/min/1.73 m
2
). 

 

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 (eg. due to blood loss, severe prolonged diarrhoea, prolonged vomiting, etc.), heart 

disease, liver disease, diabetes mellitus or kidney disease. The concomitant use of aliskiren and 

ACEIs or ARBs is contraindicated in patients with renal impairment (GFR < 60 ml/min/1.73 m
2
). 

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. 

 

Increases in serum potassium have been observed with aliskiren in post-marketing experience and 

these may be exacerbated by concomitant use of other agents acting on the RAAS or by non-steroidal 

anti-inflammatory drugs (NSAIDs). Consistent with standard medical practice, periodic determination 

of renal function including serum electrolytes is advised if co-administration is considered necessary. 

 

Renal artery stenosis 

No controlled clinical data are available on the use of Riprazo in patients with unilateral or bilateral 

renal artery stenosis, or stenosis to a solitary kidney. However, as with other medicinal products 

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. 

 

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4.5 Interaction with other medicinal products and other forms of interaction 

 

Contraindicated (see section 4.3) 

Dual RAAS blockade 

The combination of aliskiren with ARBs or ACEIs is contraindicated in patients with diabetes 

mellitus or renal impairment (GFR < 60 ml/min/1.73 m
2
) and is not recommended in other patients 

(see sections 4.3, 4.4 and 5.1). 

 

P-glycoprotein (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 (see section 4.2) 

Grapefruit juice 

Administration of grapefruit juice with aliskiren resulted in a decrease in AUC and Cmax of aliskiren. 

Co-administration 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. This decrease is 

likely due to an inhibition of organic anion transporting polypeptide-mediated uptake of aliskiren by 

grapefruit juice in the gastrointestinal tract. Therefore, because of the risk of therapeutic failure, 

grapefruit juice should not be taken together with Riprazo. 

 

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. Rifampicin, which is an inducer of P-gp, reduced 

aliskiren bioavailability by approximately 50% in a clinical study. Other inducers of P-gp (St. John’s 

wort) might decrease the bioavailability of Riprazo. Although this has not been investigated for 

aliskiren, it is known that P-gp also controls tissue uptake of a variety of substrates and P-gp 

inhibitors can increase the tissue-to-plasma concentration ratios. Therefore, P-gp inhibitors may 

increase tissue levels more than plasma levels. The potential for drug interactions at the P-gp site will 

likely depend on the degree of inhibition of this transporter. 

 

Moderate P-gp inhibitors 

Co-administration of ketoconazole (200 mg) or verapamil (240 mg) with aliskiren (300 mg) resulted 

in a 76% or 97% increase in aliskiren AUC, respectively. The change in plasma levels of aliskiren in 

the presence of ketoconazole or verapamil is expected to be within the range that would be achieved if 

the dose of aliskiren were doubled; aliskiren doses of up to 600 mg, or twice the highest 

recommended therapeutic dose, have been found to be well tolerated in controlled clinical trials. 

Preclinical studies indicate that aliskiren and ketoconazole co-administration enhances aliskiren 

gastrointestinal absorption and decreases biliary excretion. Therefore, caution should be exercised 

when aliskiren is administered with ketoconazole, verapamil or other moderate P-gp inhibitors 

(clarithromycin, telithromycin, erythromycin, amiodarone). 

 

Medicinal products affecting serum potassium levels 

Concomitant use of other agents affecting the RAAS, of NSAIDs or of agents that increase serum 

potassium levels (e.g. potassium-sparing diuretics, potassium supplements, salt substitutes containing 

potassium, heparin) may lead to increases in serum potassium. If co-medication with an agent 

affecting the level of serum potassium is considered necessary, caution is advisable. The combination 

of aliskiren with ARBs or ACEIs is contraindicated in patients with diabetes mellitus or renal 

impairment (GFR < 60 ml/min/1.73 m
2
) and is not recommended in other patients (see sections 4.3, 

4.4 and 5.1). 

 

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Non-steroidal anti-inflammatory drugs (NSAIDs) 

As with other agents acting on the renin-angiotensin system, NSAIDs may reduce the anti-

hypertensive effect of aliskiren. In some patients with compromised renal function (dehydrated 

patients or elderly patients) aliskiren given concomitantly with NSAIDs may result in further 

deterioration of renal function, including possible acute renal failure, which is usually reversible. 

Therefore the combination of aliskiren with an NSAID requires caution, especially in elderly patients. 

 

Furosemide 

When aliskiren was co-administered with furosemide, the AUC and Cmax of furosemide were reduced 

by 28% and 49%, respectively. It is therefore recommended that the effects be monitored when 

initiating and adjusting furosemide therapy to avoid possible under-utilisation in clinical situations of 

volume overload. 

 

Warfarin 

The effects of Riprazo on warfarin pharmacokinetics have not been evaluated. 

 

Food interactions 

Meals (low or high fat content) have been shown to reduce the absorption of Riprazo substantially 

(see section 4.2). 

 

No interactions 

- Compounds that have been investigated in clinical pharmacokinetic studies include 

acenocoumarol, atenolol, celecoxib, pioglitazone, allopurinol, isosorbide-5-mononitrate and 

hydrochlorothiazide. No interactions have been identified. 

 

- Co-administration of aliskiren with either metformin (↓28%), amlodipine (↑29%) or cimetidine 

(↑19%) resulted in between 20% and 30% change in Cmax or AUC of Riprazo. When 

administered with atorvastatin, steady-state Riprazo AUC and Cmax increased by 50%. Co-

administration of Riprazo had no significant impact on atorvastatin, metformin or amlodipine 

pharmacokinetics. As a result no dose adjustment for Riprazo or these co-administered 

medicinal products is necessary. 

 

- Digoxin and verapamil bioavailability may be slightly decreased by Riprazo. 

 

- CYP450 interactions 

Aliskiren does not inhibit the CYP450 isoenzymes (CYP1A2, 2C8, 2C9, 2C19, 2D6, 2E1 and 3A). 

Aliskiren does not induce CYP3A4. Therefore aliskiren is not expected to affect the systemic 

exposure of substances that inhibit, induce or are metabolised by these enzymes. Aliskiren is 

metabolised minimally by the cytochrome P450 enzymes. Hence, interactions due to inhibition or 

induction of CYP450 isoenzymes are not expected. However, CYP3A4 inhibitors often also affect P-

gp. Increased aliskiren exposure during co-administration of CYP3A4 inhibitors that also inhibit P-gp 

can therefore be expected (see other P-gp references in section 4.5). 

 

- P-gp substrates or weak inhibitors 

No relevant interactions with atenolol, digoxin, amlodipine or cimetidine have been observed. When 

administered with atorvastatin (80 mg), steady-state aliskiren (300 mg) AUC and Cmax increased by 

50%. In experimental animals, it has been shown that P-gp is a major determinant of Riprazo 

bioavailability. Inducers of P-gp (St. John’s wort, rifampicin) might therefore decrease the 

bioavailability of Riprazo. 

 

- Organic anion transporting polypeptide (OATP) inhibitors 

Preclinical studies indicate that aliskiren might be a substrate of organic anion transporting 

polypeptides. Therefore, the potential exists for interactions between OATP inhibitors and aliskiren 

when administered concomitantly (see interaction with Grapefruit juice). 

 

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4.6 Fertility, pregnancy and lactation 

 

Pregnancy 

There are no data on the use of aliskiren in pregnant women. Riprazo 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, 

Riprazo 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, Riprazo should be discontinued accordingly. 

 

Breast-feeding 

It is not known whether aliskiren is excreted in human milk. Riprazo was secreted in the milk of 

lactating rats. Its use is therefore not recommended in women who are breast-feeding. 

 

Fertility 

There are no clinical data on fertility. 

 

4.7 Effects on ability to drive and use machines 

 

Riprazo has negligible influence on the ability to drive and use machines. However, when driving 

vehicles or operating machinery it must be borne in mind that dizziness or weariness may occasionally 

occur when taking Riprazo. 

 

4.8 Undesirable effects 

 

Summary of the safety profile 

Riprazo 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 incidence of adverse reactions showed no 

association with gender, age, body mass index, race or ethnicity. 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. 

 

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Tabulated list of adverse reactions: 

The adverse drug reactions (Table 1) 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). Within each frequency grouping, undesirable effects are presented 

in order of decreasing seriousness. 

 

Table 1 

 

Immune system disorders 

 Rare: Anaphylactic reactions, hypersensitivity reactions 

Nervous system disorders 

 Common: Dizziness 

Cardiac disorders 

 Uncommon: Palpitations 

Vascular disorders 

 Uncommon: Hypotension 

Respiratory, thoracic and mediastinal disorders 

 Uncommon: Cough 

Gastrointestinal disorders 

 Common: Diarrhoea 

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 

General disorders and administration site conditions 

 Uncommon: Oedema peripheral 

Investigations 

 Common: Hyperkalaemia 

 Uncommon: Liver enzyme increased 

 Rare: Haemoglobin decreased, haematocrit decreased, blood creatinine 

increased 

 

Description of selected adverse reactions 

Hypersensitivity reactions including anaphylactic reactions and angioedema have occurred during 

treatment with aliskiren. 

 

In controlled clinical trials, angioedema and hypersensitivity reactions occurred rarely during 

treatment with aliskiren with rates comparable to treatment with placebo or comparators. 

 

Cases of angioedema or symptoms suggestive of angioedema (swelling of the face, lips, throat and/or 

tongue) have also been reported in post-marketing experience. A number of these patients had a 

history of angioedema or symptoms suggestive of angioedema which in some cases was associated 

with the administration of other medicines known to cause angioedema, including RAAS blockers 

(ACEIs or ARBs). 

 

In post-marketing experience, cases of angioedema or angioedema-like reactions have been reported 

when aliskiren was co-administered with ACEIs and/or ARBs. 

 

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23 

Hypersensitivity reactions including anaphylactic reactions have also been reported in post-marketing 

experience (see section 4.4). 

 

In the event of any signs suggesting a hypersensitivity reaction/angioedema (in particular difficulties 

in breathing or swallowing, rash, itching, hives or swelling of the face, extremities, eyes, lips and/or 

tongue, dizziness) patients should discontinue treatment and contact the physician (see section 4.4). 

 

Arthralgia has been reported in post-marketing experience. In some cases this occurred as part of a 

hypersensitivity reaction. 

 

In post-marketing experience, renal dysfunction and cases of acute renal failure have been reported in 

patients at risk (see section 4.4). 

 

Laboratory findings 

In controlled clinical trials, clinically relevant changes in standard laboratory parameters were 

uncommonly associated with the administration of Riprazo. In clinical studies in hypertensive 

patients, Riprazo had no clinically important effects on total cholesterol, high density lipoprotein 

cholesterol (HDL-C), fasting triglycerides, fasting glucose or uric acid. 

 

Haemoglobin and haematocrit: Small decreases in haemoglobin and haematocrit (mean decreases of 

approximately 0.05 mmol/l and 0.16 volume percent, respectively) were observed. No patients 

discontinued therapy due to anaemia. This effect is also seen with other agents acting on the renin-

angiotensin system, such as ACEIs and ARBs. 

 

Serum potassium: Increases in serum potassium have been observed with aliskiren and these may be 

exacerbated by concomitant use of other agents acting on the RAAS or by NSAIDs. Consistent with 

standard medical practice, periodic determination of renal function including serum electrolytes is 

advised if co-administration is considered necessary. The combination of aliskiren with ARBs or 

ACEIs is contraindicated in patients with diabetes mellitus or renal impairment (GFR 

< 60 ml/min/1.73 m
2
) and is not recommended in other patients (see sections 4.3, 4.4 and 5.1). 

 

4.9 Overdose 

 

Symptoms 

Limited data are available related to overdose in humans. The most likely manifestations of 

overdosage would be hypotension, related to the antihypertensive effect of aliskiren. 

 

Treatment 

If symptomatic hypotension should occur, supportive treatment should be initiated. 

 

In a study conducted in patients with end stage renal disease (ESRD) receiving haemodialysis, 

dialysis clearance of aliskiren was low (< 2% of oral clearance). Therefore dialysis is not adequate to 

treat aliskiren over-exposure. 

 

 

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24 

5. PHARMACOLOGICAL PROPERTIES 

 

5.1 Pharmacodynamic properties 

 

Pharmacotherapeutic group: Agents acting on the renin-angiotensin system; renin inhibitor, ATC 

code: C09XA02 

 

Aliskiren is an orally active, non-peptide, potent and selective direct inhibitor of human renin. 

 

By inhibiting the enzyme renin, aliskiren inhibits the RAAS at the point of activation, blocking the 

conversion of angiotensinogen to angiotensin I and decreasing levels of angiotensin I and angiotensin 

II. Whereas other agents that inhibit the RAAS (ACEI and angiotensin II receptor blockers (ARB)) 

cause a compensatory rise in plasma renin activity (PRA), treatment with aliskiren decreases PRA in 

hypertensive patients by approximately 50 to 80%. Similar reductions were found when aliskiren was 

combined with other antihypertensive agents. The clinical implications of the differences in effect on 

PRA are not known at the present time. 

 

Hypertension 

In hypertensive patients, once-daily administration of Riprazo at doses of 150 mg and 300 mg 

provided dose-dependent reductions in both systolic and diastolic blood pressure that were maintained 

over the entire 24-hour dose interval (maintaining benefit in the early morning) with a mean peak to 

trough ratio for diastolic response of up to 98% for the 300 mg dose. 85 to 90% of the maximal blood-

pressure-lowering effect was observed after 2 weeks. The blood-pressure-lowering effect was 

sustained during long-term treatment, and was independent of age, gender, body mass index and 

ethnicity. Riprazo has been studied in 1,864 patients aged 65 years or older, and in 426 patients aged 

75 years or older. 

 

Riprazo monotherapy studies have shown blood pressure lowering effects comparable to other classes 

of antihypertensive agents including ACEI and ARB. Compared to a diuretic (hydrochlorothiazide - 

HCTZ), Riprazo 300 mg lowered systolic/diastolic blood pressure by 17.0/12.3 mmHg, compared to 

14.4/10.5 mmHg for HCTZ 25 mg after 12 weeks of treatment. 

 

Combination therapy studies are available for Riprazo added to the diuretic hydrochlorothiazide, the 

calcium channel blocker amlodipine and the beta blocker atenolol. These combinations were well 

tolerated. Riprazo induced an additive blood-pressure-lowering effect when added to 

hydrochlorothiazide. In patients who did not adequately respond to 5 mg of the calcium channel 

blocker amlodipine, the addition of Riprazo 150 mg had a blood-pressure-lowering effect similar to 

that obtained by increasing amlodipine dose to 10 mg, but had a lower incidence of oedema (aliskiren 

150 mg/amlodipine 5 mg 2.1% vs. amlodipine 10 mg 11.2%). 

 

The efficacy and safety of aliskiren-based therapy were compared to ramipril-based therapy in a 9-

month non-inferiority study in 901 elderly patients (≥ 65 years) with essential systolic hypertension. 

Aliskiren 150 mg or 300 mg per day or ramipril 5 mg or 10 mg per day were administered for 

36 weeks with optional add-on therapy of hydrochlorothiazide (12.5 mg or 25 mg) at week 12, and 

amlodipine (5 mg or 10 mg) at week 22. Over the 12 week period, aliskiren monotherapy lowered 

systolic/diastolic blood pressure by 14.0/5.1 mmHg, compared to 11.6/3.6 mmHg for ramipril, 

consistent with aliskiren being non-inferior to ramipril at the dosages chosen and the differences in 

systolic and diastolic blood pressure were statistically significant. Tolerability was comparable in 

both treatment arms, however cough was more often reported with the ramipril regimen than the 

aliskiren regimen (14.2% vs. 4.4%), whilst diarrhoea was more common with the aliskiren regimen 

than for the ramipril regimen (6.6% vs. 5.0%). 

 

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25 

In a 8-week study in 754 hypertensive elderly (≥ 65 years) and very elderly patients (30% ≥ 75 years) 

aliskiren at doses of 75 mg, 150 mg and 300 mg provided statistically significant superior reduction in 

blood pressure (both systolic and diastolic) when compared to placebo. No additional blood pressure 

lowering effect was detected with 300 mg aliskiren compared to 150 mg aliskiren. All three doses 

were well tolerated in both elderly and very elderly patients. 

 

In obese hypertensive patients who did not adequately respond to HCTZ 25 mg, add-on treatment with 

Riprazo 300 mg provided additional blood pressure reduction that was comparable to add-on 

treatment with irbesartan 300 mg or amlodipine 10 mg. 

 

There has been no evidence of first-dose hypotension and no effect on pulse rate in patients treated in 

controlled clinical studies. Excessive hypotension was uncommonly (0.1%) seen in patients with 

uncomplicated hypertension treated with Riprazo alone. Hypotension was also uncommon (<1%) 

during combination therapy with other antihypertensive agents. With cessation of treatment, blood 

pressure gradually returned towards baseline levels over a period of several weeks, with no evidence 

of a rebound effect for blood pressure or PRA. 

 

In a 36-week study involving 820 patients with ischaemic left ventricular dysfunction, no changes in 

ventricular remodelling as assessed by left ventricular end systolic volume were detected with 

aliskiren compared to placebo on top of background therapy. 

 

The combined rates of cardiovascular death, hospitalisation for heart failure, recurrent heart attack, 

stroke and resuscitated sudden death were similar in the aliskiren group and the placebo group. 

However, in patients receiving aliskiren there was a significantly higher rate of hyperkalaemia, 

hypotension and kidney dysfunction when compared to the placebo group. 

 

Aliskiren was evaluated for cardiovascular and/or renal benefit in a double-blind placebo controlled 

randomised trial in 8,606 patients with type 2 diabetes and chronic kidney disease (evidenced by 

proteinuria and/or GFR < 60 ml/min/1.73 m
2
) with or without cardiovascular disease. In most patients 

arterial blood pressure was well controlled at baseline. The primary endpoint was a composite of 

cardiovascular and renal complications. 

 

In this study, aliskiren 300 mg was compared to placebo when added to standard of care which 

included either an angiotensin converting enzyme inhibitor or an angiotensin receptor blocker. The 

study was discontinued prematurely because the participants were unlikely to benefit from aliskiren. 

Preliminary study results indicated a hazard ratio for the primary endpoint of 1.09 in favour of 

placebo (95% Confidence Interval: 0.97, 1.22, 2-sided p=0.17). In addition, an increased incidence of 

serious adverse outcomes was observed with aliskiren compared to placebo for renal complications 

(4.7% versus 3.3%), hyperkalaemia (36.9% versus 27.1%), hypotension (18.4% versus 14.6%) and 

stroke (2.7% versus 2.0%). The increased incidence of non-fatal stroke was greater in patients with 

renal insufficiency. 

 

Beneficial effects of Riprazo on mortality and cardiovascular morbidity and target organ damage are 

currently unknown. 

 

Cardiac electrophysiology 

No effect on QT interval was reported in a randomised, double-blind, placebo, and active-controlled 

study using standard and Holter electrocardiography. 

 

Paediatric population 

The European Medicines Agency has deferred the obligation to submit the results of studies with 

Riprazo in one or more subsets of the paediatric population in hypertension (see section 4.2 for 

information on paediatric use). 

 

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26 

5.2 Pharmacokinetic properties 

 

Absorption 

Following oral absorption, peak plasma concentrations of aliskiren are reached after 1-3 hours. The 

absolute bioavailability of aliskiren is approximately 2-3%. Meals with a high fat content reduce Cmax 

by 85% and AUC by 70%. At steady state meals with low fat content reduce Cmax by 76% and AUC0-

tau by 67% in hypertensive patients. Steady-state-plasma concentrations are reached within 5-7 days 

following once-daily administration and steady-state levels are approximately 2-fold greater than with 

the initial dose. 

 

Distribution 

Following intravenous administration, the mean volume of distribution at steady state is 

approximately 135 litres, indicating that aliskiren distributes extensively into the extravascular space. 

Aliskiren plasma protein binding is moderate (47-51%) and independent of the concentration. 

 

Biotransformation and elimination 

The mean half-life is about 40 hours (range 34-41 hours). Aliskiren is mainly eliminated as unchanged 

compound in the faeces (78%). Approximately 1.4% of the total oral dose is metabolised. The enzyme 

responsible for this metabolism is CYP3A4. Approximately 0.6% of the dose is recovered in urine 

following oral administration. Following intravenous administration, the mean plasma clearance is 

approximately 9 l/h. 

 

Linearity 

Exposure to aliskiren increased more than in proportion to the increase in dose. After single dose 

administration in the dose range of 75 to 600 mg, a 2-fold increase in dose results in a ~2.3 and 2.6-

fold increase in AUC and Cmax, respectively. At steady state the non-linearity may be more 

pronounced. Mechanisms responsible for deviation from linearity have not been identified. A possible 

mechanism is saturation of transporters at the absorption site or at the hepatobiliary clearance route. 

 

Characteristics in patients 

Aliskiren is an effective once-a-day antihypertensive treatment in adult patients, regardless of gender, 

age, body mass index and ethnicity. 

 

The AUC is 50% higher in elderly (>65 years) than in young subjects. Gender, weight and ethnicity 

have no clinically relevant influence on aliskiren pharmacokinetics. 

 

The pharmacokinetics of aliskiren were evaluated in patients with varying degrees of renal 

insufficiency. Relative AUC and Cmax of aliskiren in subjects with renal impairment ranged between 

0.8 to 2 times the levels in healthy subjects following single dose administration and at steady state. 

These observed changes, however, did not correlate with the severity of renal impairment. No 

adjustment of the initial dosage of Riprazo is required in patients with mild to moderate renal 

impairment (see sections 4.2 and 4.4). Riprazo is not recommended in patients with severe renal 

impairment (glomerular filtration rate (GFR) < 30 ml/min/1.73 m
2
). Concomitant use of Riprazo with 

ARBs or ACEIs is contraindicated in patients with renal impairment (GFR < 60 ml/min/1.73 m
2
) (see 

section 4.3). 

 

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27 

The pharmacokinetics of aliskiren were evaluated in patients with end stage renal disease receiving 

haemodialysis. Administration of a single oral dose of 300 mg aliskiren was associated with very 

minor changes in the pharmacokinetics of aliskiren (change in Cmax of less than 1.2 fold; increase in 

AUC of up to 1.6 fold) compared to matched healthy subjects. Timing of haemodialysis did not 

significantly alter the pharmacokinetics of aliskiren in ESRD patients. Therefore, if administration of 

aliskiren in ESRD patients receiving haemodialysis is considered necessary, no dose adjustment is 

warranted in these patients. However, the use of aliskiren is not recommended in patients with severe 

renal impairment (see section 4.4). 

 

The pharmacokinetics of aliskiren were not significantly affected in patients with mild to severe liver 

disease. Consequently, no adjustment of the initial dose of aliskiren is required in patients with mild 

to severe hepatic impairment. 

 

5.3 Preclinical safety data 

 

Carcinogenic potential was assessed in a 2-year rat study and a 6-month transgenic mouse study. No 

carcinogenic potential was detected. One colonic adenoma and one caecal adenocarcinoma recorded 

in rats at the dose of 1,500 mg/kg/day were not statistically significant. Although aliskiren has known 

irritation potential, safety margins obtained in humans at the dose of 300 mg during a study in healthy 

volunteers were considered to be appropriate at 9-11-fold based on faecal concentrations or 6-fold 

based on mucosa concentrations in comparison with 250 mg/kg/day in the rat carcinogenicity study. 

 

Aliskiren was devoid of any mutagenic potential in the in vitro and in vivo mutagenicity studies. The 

assays included in vitro assays in bacterial and mammalian cells and in vivo assessments in rats. 

 

Reproductive toxicity studies with aliskiren did not reveal any evidence of embryofoetal toxicity or 

teratogenicity at doses up to 600 mg/kg/day in rats or 100 mg/kg/day in rabbits. Fertility, pre-natal 

development and post-natal development were unaffected in rats at doses up to 250 mg/kg/day. The 

doses in rats and rabbits provided systemic exposures of 1 to 4 and 5 times higher, respectively, than 

the maximum recommended human dose (300 mg). 

 
Safety pharmacology studies did not reveal any adverse effects on central nervous, respiratory or 

cardiovascular function. Findings during repeat-dose toxicity studies in animals were consistent with 

the known local irritation potential or the expected pharmacological effects of aliskiren. 

 

 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 

 

Crospovidone 

Magnesium stearate 

Cellulose, microcrystalline 

Povidone 

Silica, colloidal anhydrous 

Hypromellose 

Macrogol 

Talc 

Iron oxide, black (E 172) 

Iron oxide, red (E 172) 

Titanium dioxide (E 171) 

 

6.2 Incompatibilities 

 

Not applicable 

 

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28 

6.3 Shelf life 

 

2 years 

 

6.4 Special precautions for storage 

 

Do not store above 30C. Store in the original package in order to protect from moisture. 

 

6.5 Nature and contents of container 

 

PA/Alu/PVC – Alu blisters: 

Packs containing 7, 14, 28, 30, 50, 56, 84, 90, 98 or 280 tablets. 

Packs containing 84 (3x28), 90 (3x30), 98 (2x49) or 280 (20x14) tablets are multi-packs. 

 

PVC/polychlorotrifluoroethylene (PCTFE) – Alu blisters: 

Packs containing 14, 28, 30, 50, 56, 90, 98 or 280 tablets. 

Packs containing 98 (2x49) or 280 (20x14) tablets are multi-packs. 

Packs containing 56 and 98 (2x49) tablets are perforated unit-dose blisters. 

 

Not all pack sizes may be marketed. 

 

6.6 Special precautions for disposal 

 

Any unused medicinal product or waste material should be disposed of in accordance with local 

requirements. 

 

 

7. MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Wimblehurst Road 

Horsham 

West Sussex, RH12 5AB 

United Kingdom 

 

 

8. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/07/409/011-020 

EU/1/07/409/031-040 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 

 

Date of first authorisation: 22 August 2007 

Date of latest renewal: 

 

 

10. DATE OF REVISION OF THE TEXT 

 

 

Detailed information on this medicinal product is available on the website of the European Medicines 

Agency http://www.ema.europa.eu 

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29 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX II 

 

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 

AND USE 

 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 

 

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30 

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 

 

Name and address of the manufacturer responsible for batch release 

 

Novartis Farma S.p.A. 

Via Provinciale Schito 131 

I-80058 Torre Annunziata/NA 

Italy 

 

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 

 

Medicinal product subject to medical prescription. 

 

 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 

 

Pharmacovigilance system 

The MAH must ensure that the system of pharmacovigilance presented in Module 1.8.1 of the 

Marketing Authorisation, is in place and functioning before and whilst the medicinal product is on the 

market. 

 

Risk Management Plan (RMP) 

The MAH shall perform the pharmacovigilance activities detailed in the Pharmacovigilance Plan, as 

agreed in the RMP presented in Module 1.8.2 of the Marketing Authorisation and any subsequent 

updates of the RMP agreed by the Committee for Medicinal Products for Human Use (CHMP). 

 

As per the CHMP Guideline on Risk Management Systems for medicinal products for human use, the 

updated RMP should be submitted at the same time as the next Periodic Safety Update Report 

(PSUR). 

 

In addition, an updated RMP should be submitted within 1 month after the Commission Decision of 

the renewal procedure. The RMP shall include the following: 

 Deadlines for submission of the APOLLO study results. 

 A description and timelines for the new study replacing APOLLO and designed to elucidate 

efficacy and safety in the elderly, including gastrointestinal cancer as a pre-specified endpoint. 

 Timelines to submit further data on colorectal hyperplasia events from ALTITUDE study. 

 A commitment to submit the final study report of the epidemiological study on ischaemic 

colitis. 

 A description and timelines for the new observational study on incidence of colorectal 

hyperplasia in aliskiren-treated patients. 

 

In addition, an updated RMP should be submitted: 

 When new information is received that may impact on the current Safety Specification, 

Pharmacovigilance Plan or risk minimisation activities. 

 Within 60 days of an important (pharmacovigilance or risk minimisation) milestone being 

reached. 

 At the request of the European Medicines Agency. 

 

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31 

PSURs 

The PSUR cycle for the medicinal product should follow the yearly cycle until otherwise agreed by 

the CHMP. 

 

 CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 

 

Not applicable. 

 

 OBLIGATION TO CONDUCT POST-AUTHORISATION MEASURES 

 

The MAH shall complete, within the stated timeframe, the following measures: 

 

Description Due date 

The MAH shall submit the final results and study report for the active treatment 

phase of the ALTITUDE study when available 

31 July 2012 

The MAH shall submit an updated risk management plan (RMP) that 

adequately describes all the safety concerns, the pharmacovigilance activities 

and the interventions designed to identify, characterise, prevent or minimise the 

risks within a month following the Commission Decision of the renewal 

procedure (EMEA/H/C/853/R/068). The RMP shall include: 
- Deadlines for submission of the APOLLO study results. 

- A description and timelines for the new study replacing APOLLO and 

designed to elucidate efficacy and safety in the elderly, including 

gastrointestinal cancer as a pre-specified endpoint. 

- Timelines to submit further data on colorectal hyperplasia events from 

ALTITUDE study. 

- A commitment to submit the final study report of the epidemiological 

study on ischaemic colitis. 

- A description and timelines for the new observational study on incidence 

of colorectal hyperplasia in aliskiren-treated patients. 

Within a month 

following the 

Commission 

Decision of the 

renewal 

procedure 

 

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32 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX III 

 

LABELLING AND PACKAGE LEAFLET 

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33 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

A. LABELLING 

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34 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

FOLDING BOX FOR UNIT PACK CONTAINING PA/ALU/PVC BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Riprazo 150 mg film-coated tablets 

Aliskiren 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each film-coated tablet contains 150 mg aliskiren (as hemifumarate). 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

7 film-coated tablets 

14 film-coated tablets 

28 film-coated tablets 

30 film-coated tablets 

50 film-coated tablets 

56 film-coated tablets 

90 film-coated tablets 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Oral use. 

Read the package leaflet before use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

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35 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

Store in the original package in order to protect from moisture. 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Wimblehurst Road 

Horsham 

West Sussex, RH12 5AB 

United Kingdom 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/07/409/001 7 film-coated tablets 

EU/1/07/409/002 14 film-coated tablets 

EU/1/07/409/003 28 film-coated tablets 

EU/1/07/409/004 30 film-coated tablets 

EU/1/07/409/005 50 film-coated tablets 

EU/1/07/409/006 56 film-coated tablets 

EU/1/07/409/008 90 film-coated tablets 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Riprazo 150 mg 
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36 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

FOLDING BOX FOR UNIT PACK CONTAINING PCTFE/PVC BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Riprazo 150 mg film-coated tablets 

Aliskiren 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each film-coated tablet contains 150 mg aliskiren (as hemifumarate). 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

14 film-coated tablets 

28 film-coated tablets 

30 film-coated tablets 

50 film-coated tablets 

56 film-coated tablets 

90 film-coated tablets 

98 film-coated tablets 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Oral use. 

Read the package leaflet before use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

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37 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

Store in the original package in order to protect from moisture. 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Wimblehurst Road 

Horsham 

West Sussex, RH12 5AB 

United Kingdom 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/07/409/021 14 film-coated tablets 

EU/1/07/409/022 28 film-coated tablets 

EU/1/07/409/023 30 film-coated tablets 

EU/1/07/409/024 50 film-coated tablets 

EU/1/07/409/025 56 film-coated tablets 

EU/1/07/409/026 56 film-coated tablets (perforated unit-dose blister) 

EU/1/07/409/027 90 film-coated tablets 

EU/1/07/409/028 98 film-coated tablets 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Riprazo 150 mg 

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38 

 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

BLISTER 

BLISTER (CALENDAR) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Riprazo 150 mg film-coated tablets 

Aliskiren 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 
 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. OTHER 

 

Monday 

Tuesday 

Wednesday 

Thursday 

Friday 

Saturday 

Sunday 

 

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39 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

INTERMEDIATE CARTON OF MULTIPACKS (WITHOUT BLUE BOX) CONTAINING 

PA/ALU/PVC BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Riprazo 150 mg film-coated tablets 

Aliskiren 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each film-coated tablet contains 150 mg aliskiren (as hemifumarate). 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

14 film-coated tablets 

Component of a multipack comprising 20 packs, each containing 14 tablets. 

28 film-coated tablets 

Component of a multipack comprising 3 packs, each containing 28 tablets. 

49 film-coated tablets 

Component of a multipack comprising 2 packs, each containing 49 tablets. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Oral use. 

Read the package leaflet before use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

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40 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

Store in the original package in order to protect from moisture. 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Wimblehurst Road 

Horsham 

West Sussex, RH12 5AB 

United Kingdom 
 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/07/409/007 84 film-coated tablets (3x28) 

EU/1/07/409/009 98 film-coated tablets (2x49) 

EU/1/07/409/010 280 film-coated tablets (20x14) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Riprazo 150 mg 

Me
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ina
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no

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41 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER CARTON OF MULTIPACKS (INCLUDING BLUE BOX) CONTAINING 

PA/ALU/PVC BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Riprazo 150 mg film-coated tablets 

Aliskiren 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each film-coated tablet contains 150 mg aliskiren (as hemifumarate). 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

84 film-coated tablets 

Multipack comprising 3 packs, each containing 28 tablets. 

98 film-coated tablets 

Multipack comprising 2 packs, each containing 49 tablets. 

280 film-coated tablets 

Multipack comprising 20 packs, each containing 14 tablets. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Oral use. 

Read the package leaflet before use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

Me
dic

ina
l p

ro
du

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no

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th
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42 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

Store in the original package in order to protect from moisture. 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Wimblehurst Road 

Horsham 

West Sussex, RH12 5AB 

United Kingdom 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/07/409/007 84 film-coated tablets (3x28) 

EU/1/07/409/009 98 film-coated tablets (2x49) 

EU/1/07/409/010 280 film-coated tablets (20x14) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Riprazo 150 mg 

Me
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43 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

INTERMEDIATE CARTON OF MULTIPACKS (WITHOUT BLUE BOX) CONTAINING 

PCTFE/PVC BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Riprazo 150 mg film-coated tablets 

Aliskiren 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each film-coated tablet contains 150 mg aliskiren (as hemifumarate). 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

14 film-coated tablets 

Component of a multipack comprising 20 packs, each containing 14 tablets. 

49 film-coated tablets 

Component of a multipack comprising 2 packs, each containing 49 tablets. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Oral use. 

Read the package leaflet before use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

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no

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44 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

Store in the original package in order to protect from moisture. 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Wimblehurst Road 

Horsham 

West Sussex, RH12 5AB 

United Kingdom 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/07/409/029 98 film-coated tablets (2x49) (perforated unit-dose blister) 

EU/1/07/409/030 280 film-coated tablets (20x14) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Riprazo 150 mg 

Me
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no

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45 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER CARTON OF MULTIPACKS (INCLUDING BLUE BOX) CONTAINING 

PCTFE/PVC BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Riprazo 150 mg film-coated tablets 

Aliskiren 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each film-coated tablet contains 150 mg aliskiren (as hemifumarate). 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

280 film-coated tablets 

Multipack comprising 20 packs, each containing 14 tablets. 

98 film-coated tablets 

Multipack comprising 2 packs, each containing 49 tablets. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Oral use. 

Read the package leaflet before use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

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no

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46 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

Store in the original package in order to protect from moisture. 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Wimblehurst Road 

Horsham 

West Sussex, RH12 5AB 

United Kingdom 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/07/409/029 98 film-coated tablets (2x49) (perforated unit-dose blister) 

EU/1/07/409/030 280 film-coated tablets (20x14) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Riprazo 150 mg 

Me
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no

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th
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47 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

FOLDING BOX FOR UNIT PACK CONTAINING PA/ALU/PVC BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Riprazo 300 mg film-coated tablets 

Aliskiren 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each film-coated tablet contains 300 mg aliskiren (as hemifumarate). 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

7 film-coated tablets 

14 film-coated tablets 

28 film-coated tablets 

30 film-coated tablets 

50 film-coated tablets 

56 film-coated tablets 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Oral use. 

Read the package leaflet before use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

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48 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

Store in the original package in order to protect from moisture. 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Wimblehurst Road 

Horsham 

West Sussex, RH12 5AB 

United Kingdom 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/07/409/011 7 film-coated tablets 

EU/1/07/409/012 14 film-coated tablets 

EU/1/07/409/013 28 film-coated tablets 

EU/1/07/409/014 30 film-coated tablets 

EU/1/07/409/015 50 film-coated tablets 

EU/1/07/409/016 56 film-coated tablets 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Riprazo 300 mg Me
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49 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

FOLDING BOX FOR UNIT PACK CONTAINING PCTFE/PVC BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Riprazo 300 mg film-coated tablets 

Aliskiren 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each film-coated tablet contains 300 mg aliskiren (as hemifumarate). 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

14 film-coated tablets 

28 film-coated tablets 

30 film-coated tablets 

50 film-coated tablets 

56 film-coated tablets 

90 film-coated tablets 

98 film-coated tablets 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Oral use 

Read the package leaflet before use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

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50 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

Store in the original package in order to protect from moisture. 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Wimblehurst Road 

Horsham 

West Sussex, RH12 5AB 

United Kingdom 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/07/409/031 14 film-coated tablets 

EU/1/07/409/032 28 film-coated tablets 

EU/1/07/409/033 30 film-coated tablets 

EU/1/07/409/034 50 film-coated tablets 

EU/1/07/409/035 56 film-coated tablets 

EU/1/07/409/036 56 film-coated tablets (perforated unit-dose blister) 

EU/1/07/409/037 90 film-coated tablets 

EU/1/07/409/038 98 film-coated tablets 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Riprazo 300 mg 

Me
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51 

 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

BLISTER 

BLISTER (CALENDAR) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Riprazo 300 mg film-coated tablets 

Aliskiren 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 
 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. OTHER 

 

Monday 

Tuesday 

Wednesday 

Thursday 

Friday 

Saturday 

Sunday 

 

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52 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

INTERMEDIATE CARTON OF MULTIPACKS (WITHOUT BLUE BOX) CONTAINING 

PA/ALU/PVC BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Riprazo 300 mg film-coated tablets 

Aliskiren 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each film-coated tablet contains 300 mg aliskiren (as hemifumarate). 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

14 film-coated tablets 

Component of a multipack comprising 20 packs, each containing 14 tablets. 

28 film-coated tablets 

Component of a multipack comprising 3 packs, each containing 28 tablets. 

30 film-coated tablets 

Component of a multipack comprising 3 packs, each containing 30 tablets. 

49 film-coated tablets 

Component of a multipack comprising 2 packs, each containing 49 tablets. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Oral use. 

Read the package leaflet before use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

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53 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

Store in the original package in order to protect from moisture. 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Wimblehurst Road 

Horsham 

West Sussex, RH12 5AB 

United Kingdom 
 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/07/409/017 84 film-coated tablets (3x28) 

EU/1/07/409/018 90 film-coated tablets (3x30) 

EU/1/07/409/019 98 film-coated tablets (2x49) 

EU/1/07/409/020 280 film-coated tablets (20x14) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Riprazo 300 mg 

 Me
dic

ina
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du

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no

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54 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER CARTON OF MULTIPACKS (INCLUDING BLUE BOX) CONTAINING 

PA/ALU/PVC BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Riprazo 300 mg film-coated tablets 

Aliskiren 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each film-coated tablet contains 300 mg aliskiren (as hemifumarate). 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

84 film-coated tablets 

Multipack comprising 3 packs, each containing 28 tablets. 

90 film-coated tablets 

Multipack comprising 3 packs, each containing 30 tablets. 

98 film-coated tablets 

Multipack comprising 2 packs, each containing 49 tablets. 

280 film-coated tablets 

Multipack comprising 20 packs, each containing 14 tablets. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Oral use. 

Read the package leaflet before use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

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55 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

Store in the original package in order to protect from moisture. 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Wimblehurst Road 

Horsham 

West Sussex, RH12 5AB 

United Kingdom 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/07/409/017 84 film-coated tablets (3x28) 

EU/1/07/409/018 90 film-coated tablets (3x30) 

EU/1/07/409/019 98 film-coated tablets (2x49) 

EU/1/07/409/020 280 film-coated tablets (20x14) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Riprazo 300 mg 

 Me
dic

ina
l p

ro
du

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no

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ng

er
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th
or

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d



56 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

INTERMEDIATE CARTON OF MULTIPACKS (WITHOUT BLUE BOX) CONTAINING 

PCTFE/PVC BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Riprazo 300 mg film-coated tablets 

Aliskiren 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each film-coated tablet contains 300 mg aliskiren (as hemifumarate). 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

14 film-coated tablets 

Component of a multipack comprising 20 packs, each containing 14 tablets. 

49 film-coated tablets 

Component of a multipack comprising 2 packs, each containing 49 tablets. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Oral use 

Read the package leaflet before use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

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no

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57 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

Store in the original package in order to protect from moisture. 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Wimblehurst Road 

Horsham 

West Sussex, RH12 5AB 

United Kingdom 
 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/07/409/039 98 film-coated tablets (2x49) (perforated unit-dose blister) 

EU/1/07/409/040 280 film-coated tablets (20x14) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Riprazo 300 mg 

Me
dic

ina
l p

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du

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no

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ng

er
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th
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58 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER CARTON OF MULTIPACKS (INCLUDING BLUE BOX) CONTAINING 

PCTFE/PVC BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Riprazo 300 mg film-coated tablets 

Aliskiren 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each film-coated tablet contains 300 mg aliskiren (as hemifumarate). 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

280 film-coated tablets 

Multipack comprising 20 packs, each containing 14 tablets. 

98 film-coated tablets 

Multipack comprising 2 packs, each containing 49 tablets. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Oral use 

Read the package leaflet before use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

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59 

9. SPECIAL STORAGE CONDITIONS 

 

Do not store above 30°C. 

Store in the original package in order to protect from moisture. 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Wimblehurst Road 

Horsham 

West Sussex, RH12 5AB 

United Kingdom 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/07/409/039 98 film-coated tablets (2x49) (perforated unit-dose blister) 

EU/1/07/409/040 280 film-coated tablets (20x14) 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Riprazo 300 mg 

Me
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60 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

B. PACKAGE LEAFLET 

 

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61 

Package leaflet: information for the user 

 

Riprazo 150 mg film-coated tablets 

Aliskiren 

 

 

Read all of this leaflet carefully before you start taking this medicine because it contains 

important information for you. 

- Keep this leaflet. You may need to read it again. 

- If you have any further questions, ask your doctor or pharmacist. 

- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 

- If you get any side effects, talk to your doctor or pharmacist. This includes any possible side 

effects not listed in this leaflet. 

 

 

What is in this leaflet 

1. What Riprazo is and what it is used for 

2. What you need to know before you take Riprazo 

3. How to take Riprazo 

4. Possible side effects 

5. How to store Riprazo 

6. Contents of the pack and other information 

 

 

 

1. What Riprazo is and what it is used for 

 

Riprazo tablets contain an active substance called aliskiren. Aliskiren belongs to a class of medicines 

called renin inhibitors. Riprazo helps to lower high blood pressure in adult patients. Renin inhibitors 

reduce the amount of angiotensin II the body can produce. Angiotensin II causes blood vessels to 

tighten, which increases the blood pressure. Reducing the amount of angiotensin II allows the blood 

vessels to relax, which lowers blood pressure. 

 

High blood pressure increases the workload of the heart and arteries. If this continues for a long time, 

it can damage the blood vessels of the brain, heart and kidneys, and may result in a stroke, heart 

failure, heart attack or kidney failure. Lowering the blood pressure to a normal level reduces the risk 

of developing these disorders. 

 

 

2. What you need to know before you take Riprazo 

 

Do not take Riprazo 

- if you are allergic to aliskiren or any of the other ingredients of this medicine (listed in section 

6). If you think you may be allergic, ask your doctor for advice. 

- if you have experienced the following forms of angioedema (difficulties in breathing or 

swallowing, or swelling of the face, hands and feet, eyes, lips and/or tongue): 

- angioedema when taking aliskiren. 

- hereditary angioedema. 

- angioedema without any known cause. 

- during the last 6 months of pregnancy or if you are breast-feeding, see section Pregnancy and 

breastfeeding. 

- if you are taking ciclosporin (a medicine used in transplantation to prevent organ rejection or 

for other conditions, e.g. rheumathoid arthritis or atopic dermatitis), itraconazole (a medicine 

used to treat fungal infections) or quinidine (a medicine used to correct heart rhythm). 

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- if you have diabetes mellitus or impaired kidney function and you are treated with either of the 

following classes of medicines used to treat high blood pressure: 

- an “angiotensin converting enzyme inhibitor” such as enalapril, lisinopril, ramipril etc. 

or 

- an “angiotensin II receptor blocker” such as valsartan, telmisartan, irbesartan etc. 

 

Warnings and precautions 

Talk to your doctor before taking Riprazo: 

- if you are taking a diuretic (a type of medicine also known as “water” tablets which increases 

the amount of urine you produce). 

- if you are taking either of the following classes of medicines used to treat high blood pressure: 

- an “angiotensin converting enzyme inhibitor” such as enalapril, lisinopril, ramipril etc. 

or 

- an “angiotensin II receptor blocker” such as valsartan, telmisartan, irbesartan etc. 

- if you have impaired kidney function, your doctor will carefully consider whether Riprazo is 

suitable for you and may wish to monitor you carefully. 

- if you have already experienced angioedema (difficulties in breathing or swallowing, or 

swelling of the face, hands and feet, eyes, lips and/or tongue). If this happens, stop taking 

Riprazo and contact your doctor. 

- if you have renal artery stenosis (narrowing of the blood vessels to one or both kidneys). 

- if you have serious congestive heart failure (a type of heart disease where the heart cannot 

pump enough blood around the body). 

 

Children and adolescents 

The use of Riprazo in children and adolescents up to 18 years of age is not recommended. 

 

Elderly 

In the majority of patients aged 65 years or older, the 300 mg dose of Riprazo shows no additional 

benefit in reducing blood pressure compared to the 150 mg dose. 

 

Other medicines and Riprazo 

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 

medicines. 

 

Do not take Riprazo if you are taking ciclosporin (a medicine used in transplantation to prevent organ 

rejection or for other conditions, e.g. rheumathoid arthritis or atopic dermatitis), itraconazole (a 

medicine used to treat fungal infections) or quinidine (a medicine used to correct heart rhythm). 

 

Your doctor may need to change your dose and/or to take other precautions if you are taking one of 

the following medicines: 

- medicines that increase the amount of potassium in your blood. These include potassium-

sparing diuretics, potassium supplements. 

- furosemide, a medicine belonging to the type known as diuretics, or “water” tablets, which is 

used to increase the amount of urine you produce. 

- one of the following classes of medicines used to treat high blood pressure: 

- an “angiotensin converting enzyme inhibitor” such as enalapril, lisinopril, ramipril etc. 

or 

- an “angiotensin II receptor blocker” such as valsartan, telmisartan, irbesartan etc. 

- ketoconazole, a medicine used to treat fungal infections. 

- verapamil, a medicine used to lower high blood pressure, to correct heart rhythm or to treat 

angina pectoris. 

- certain types of pain killers called non-steroidal anti-inflammatory medicines (NSAIDs). 

 

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Riprazo with food and drink 

You should take this medicine with a light meal once a day, preferably at the same time each day. You 

should not take this medicine together with grapefruit juice. 

 

Pregnancy and breast-feeding 

Do not take this medicine if you are pregnant or breast-feeding (see section Do not take Riprazo). If 

you think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for 

advice before taking this medicine. If you become pregnant while taking this medicine, stop taking it 

immediately and talk to your doctor. 

 

Driving and using machines 

This medicine may make you feel dizzy and this can affect your ability to concentrate. Before you 

drive a vehicle, use machinery, or carry out other activities that require concentration, you should 

make sure you know how you react to the effects of this medicine. 

 

 

3. How to take Riprazo 

 

Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist 

if you are not sure. 

 

People who have high blood pressure often do not notice any signs of the problem. Many may feel 

quite normal. It is very important that you take this medicine exactly as your doctor tells you to get the 

best results and reduce the risk of side effects. Keep your appointments with the doctor even if you 

are feeling well. 

 

The usual starting dose is one 150 mg tablet once daily. The blood pressure lowering effect is present 

within two weeks after beginning treatment. 

 

Depending on how you respond to the treatment your doctor may prescribe a higher dose of one 

300 mg tablet once daily. Your doctor may prescribe Riprazo together with other medicines used to 

treat high blood pressure. 

 

Method of administration 

It is recommended that you take the tablets with some water. You should take this medicine with a 

light meal once a day, preferably at the same time each day. You should not take this medicine 

together with grapefruit juice. 

 

If you take more Riprazo than you should 

If you have accidentally taken too many Riprazo tablets, consult a doctor immediately. You may 

require medical attention. 

 

If you forget to take Riprazo 

If you forget to take a dose of Riprazo, take it as soon as you remember and then take the next dose at 

its usual time. However, if it is almost time for your next dose you should simply take the next tablet 

at the usual time. Do not take a double dose to make up for a forgotten dose. 

 

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4. Possible side effects 

 

Like all medicines, this medicine can cause side effects, although not everybody gets them. 

 

Some side effects can be serious: 

A few patients have experienced these serious side effects (may affect up to 1 in 1,000 people). If any 

of the following occur, tell your doctor straight away: 

Severe allergic reaction with symptoms such as rash, itching, swelling of face or lips or tongue, 

difficulty breathing, dizziness. 

 

Possible side effects: 

Common (may affect up to 1 in 10 people): Diarrhoea, joint pain (arthralgia), high level of potassium 

in the blood, dizziness. 

Uncommon (may affect up to 1 in 100 people): Skin rash (this may also be a sign of allergic reactions 

or angioedema – see “Rare” side effects below), kidney problems including acute renal failure 

(severely decreased urine output), swelling of hands, ankles or feet (peripheral oedema), severe skin 

reactions (toxic epidermal necrolysis and/or oral mucosal reactions - red skin, blistering of the lips, 

eyes or mouth, skin peeling, fever), low blood pressure, palpitations, cough, itching, itchy rash 

(urticaria), increased liver enzymes. 

Rare (may affect up to 1 in 1,000 people): Severe allergic reaction (anaphylactic reaction), allergic 

reactions (hypersensitivity) and angioedema (the symptoms of which can include difficulties in 

breathing or swallowing, rash, itching, hives or swelling of the face, hands and feet, eyes, lips and/or 

tongue, dizziness), increased level of creatinine in the blood, red skin (erythema). 

 

If any of these affect you severely, tell your doctor. You may need to stop Riprazo. 

 

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 

not listed in this leaflet. 

 

 

5. How to store Riprazo 

 

Keep this medicine out of the sight and reach of children. 

Do not use this medicine after the expiry date which is stated on the carton and blister. The expiry 

date refers to the last day of that month. 

Do not store above 30°C. 

Store in the original package in order to protect from moisture. 

 

 

6. Contents of the pack and other information 

 

What Riprazo contains 

- The active substance is aliskiren (as hemifumarate) 150 mg. 

- The other ingredients are crospovidone, hypromellose, magnesium stearate, macrogol, 

microcrystalline cellulose, povidone, colloidal anhydrous silica, talc, titanium dioxide (E 171), 

black iron oxide (E 172), red iron oxide (E 172). 

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What Riprazo looks like and contents of the pack 

Riprazo 150 mg film coated tablets are light-pink, biconvex round tablets, imprinted “IL” on one side 

and “NVR” on the other side. 

 

Riprazo is available in packs containing 7, 14, 28, 30, 50, 56, 84, 90, 98 or 280 tablets. Packs 

containing 84 (3x28), 98 (2x49) or 280 (20x14) tablets are multi-packs. Not all pack sizes may be 

available in your country. 

 

 

Marketing Authorisation Holder 

Novartis Europharm Limited 

Wimblehurst Road 

Horsham 

West Sussex, RH12 5AB 

United Kingdom 

 

Manufacturer 

Novartis Farma S.p.A. 

Via Provinciale Schito 131 

I-80058 Torre Annunziata/NA 

Italy 

 

For any information about this medicine, please contact the local representative of the Marketing 

Authorisation Holder: 

 

België/Belgique/Belgien 

Novartis Pharma N.V. 

Tél/Tel: +32 2 246 16 11 

 

Luxembourg/Luxemburg 

Novartis Pharma GmbH 

Tél/Tel: +49 911 273 0 

 

България 

Novartis Pharma Services Inc. 

Тел.: +359 2 489 98 28 

 

Magyarország 

Novartis Hungária Kft. Pharma 

Tel.: +36 1 457 65 00 

Česká republika 

Novartis s.r.o. 

Tel: +420 225 775 111 

 

Malta 

Novartis Pharma Services Inc. 

Tel: +356 2122 2872 

Danmark 

Novartis Healthcare A/S 

Tlf: +45 39 16 84 00 

 

Nederland 

Novartis Pharma B.V. 

Tel: +31 26 37 82 111 

Deutschland 

Novartis Pharma GmbH 

Tel: +49 911 273 0 

 

Norge 

Novartis Norge AS 

Tlf: +47 23 05 20 00 

Eesti 

Novartis Pharma Services Inc. 

Tel: +372 66 30 810 

 

Österreich 

Novartis Pharma GmbH 

Tel: +43 1 86 6570 

Ελλάδα 

Novartis (Hellas) A.E.B.E. 

Τηλ: +30 210 281 17 12 

 

Polska 

Novartis Poland Sp. z o.o. 

Tel.: +48 22 375 4888 

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66 

 

España 

Laboratorios Dr. Esteve, S.A. 

Tel: +34 93 446 60 00 

 

Portugal 

Novartis Farma - Produtos Farmacêuticos, S.A. 

Tel: +351 21 000 8600 

France 

Novartis Pharma S.A.S. 

Tél: +33 1 55 47 66 00 

 

România 

Novartis Pharma Services Romania SRL 

Tel: +40 21 31299 01 

Ireland 

Novartis Ireland Limited 

Tel: +353 1 260 12 55 

 

Slovenija 

Novartis Pharma Services Inc. 

Tel: +386 1 300 75 50 

Ísland 

Vistor hf. 

Sími: +354 535 7000 

 

Slovenská republika 

Novartis Slovakia s.r.o. 

Tel: +421 2 5542 5439 

 

Italia 

Novartis Farma S.p.A. 

Tel: +39 02 96 54 1 

Suomi/Finland 

Novartis Finland Oy 

Puh/Tel: +358 (0)10 6133 200 

 

Κύπρος 

Novartis Pharma Services Inc. 

Τηλ: +357 22 690 690 

 

Sverige 

Novartis Sverige AB 

Tel: +46 8 732 32 00 

 

Latvija 

Novartis Pharma Services Inc. 

Tel: +371 67 887 070 

 

United Kingdom 

Novartis Pharmaceuticals UK Ltd. 

Tel: +44 1276 698370 

 

Lietuva 

Novartis Pharma Services Inc. 

Tel: +370 5 269 16 50 

 

 

 

This leaflet was last revised in 

 

Other sources of information 

Detailed information on this medicine is available on the European Medicines Agency website: 

http://www.ema.europa.eu 

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Package leaflet: information for the user 

 

Riprazo 300 mg film-coated tablets 

Aliskiren 

 

 

Read all of this leaflet carefully before you start taking this medicine because it contains 

important information for you. 

- Keep this leaflet. You may need to read it again. 

- If you have any further questions, ask your doctor or pharmacist. 

- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 

- If you get any side effects, talk to your doctor or pharmacist. This includes any possible side 

effects not listed in this leaflet. 

 

 

What is in this leaflet 

1. What Riprazo is and what it is used for 

2. What you need to know before you take Riprazo 

3. How to take Riprazo 

4. Possible side effects 

5. How to store Riprazo 

6. Contents of the pack and other information 

 

 

 

1. What Riprazo is and what it is used for 

 

Riprazo tablets contain an active substance called aliskiren. Aliskiren belongs to a class of medicines 

called renin inhibitors. Riprazo helps to lower high blood pressure in adult patients. Renin inhibitors 

reduce the amount of angiotensin II the body can produce. Angiotensin II causes blood vessels to 

tighten, which increases the blood pressure. Reducing the amount of angiotensin II allows the blood 

vessels to relax, which lowers blood pressure. 

 

High blood pressure increases the workload of the heart and arteries. If this continues for a long time, 

it can damage the blood vessels of the brain, heart and kidneys, and may result in a stroke, heart 

failure, heart attack or kidney failure. Lowering the blood pressure to a normal level reduces the risk 

of developing these disorders. 

 

 

2. What you need to know before you take Riprazo 

 

Do not take Riprazo 

- if you are allergic to aliskiren or any of the other ingredients of this medicine (listed in section 

6). If you think you may be allergic, ask your doctor for advice. 

- if you have experienced the following forms of angioedema (difficulties in breathing or 

swallowing, or swelling of the face, hands and feet, eyes, lips and/or tongue): 

- angioedema when taking aliskiren. 

- hereditary angioedema. 

- angioedema without any known cause. 

- during the last 6 months of pregnancy or if you are breast-feeding, see section Pregnancy and 

breastfeeding. 

- if you are taking ciclosporin (a medicine used in transplantation to prevent organ rejection or 

for other conditions, e.g. rheumathoid arthritis or atopic dermatitis), itraconazole (a medicine 

used to treat fungal infections) or quinidine (a medicine used to correct heart rhythm). 

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68 

- if you have diabetes mellitus or impaired kidney function and you are treated with either of the 

following classes of medicines used to treat high blood pressure: 

- an “angiotensin converting enzyme inhibitor” such as enalapril, lisinopril, ramipril etc. 

or 

- an “angiotensin II receptor blocker” such as valsartan, telmisartan, irbesartan etc. 

 

Warnings and precautions 

Talk to your doctor before taking Riprazo: 

- if you are taking a diuretic (a type of medicine also known as “water” tablets which increases 

the amount of urine you produce). 

- if you are taking either of the following classes of medicines used to treat high blood pressure: 

- an “angiotensin converting enzyme inhibitor” such as enalapril, lisinopril, ramipril etc. 

or 

- an “angiotensin II receptor blocker” such as valsartan, telmisartan, irbesartan etc. 

- if you have impaired kidney function, your doctor will carefully consider whether Riprazo is 

suitable for you and may wish to monitor you carefully. 

- if you have already experienced angioedema (difficulties in breathing or swallowing, or 

swelling of the face, hands and feet, eyes, lips and/or tongue). If this happens, stop taking 

Riprazo and contact your doctor. 

- if you have renal artery stenosis (narrowing of the blood vessels to one or both kidneys). 

- if you have serious congestive heart failure (a type of heart disease where the heart cannot 

pump enough blood around the body). 

 

Children and adolescents 

The use of Riprazo in children and adolescents up to 18 years of age is not recommended. 

 

Elderly 

In the majority of patients aged 65 years or older, the 300 mg dose of Riprazo shows no additional 

benefit in reducing blood pressure compared to the 150 mg dose. 

 

Other medicines and Riprazo 

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 

medicines. 

 

Do not take Riprazo if you are taking ciclosporin (a medicine used in transplantation to prevent organ 

rejection or for other conditions, e.g. rheumathoid arthritis or atopic dermatitis), itraconazole (a 

medicine used to treat fungal infections) or quinidine (a medicine used to correct heart rhythm). 

 

Your doctor may need to change your dose and/or to take other precautions if you are taking one of 

the following medicines: 

- medicines that increase the amount of potassium in your blood. These include potassium-

sparing diuretics, potassium supplements. 

- furosemide, a medicine belonging to the type known as diuretics, or “water” tablets, which is 

used to increase the amount of urine you produce. 

- one of the following classes of medicines used to treat high blood pressure: 

- an “angiotensin converting enzyme inhibitor” such as enalapril, lisinopril, ramipril etc. 

or 

- an “angiotensin II receptor blocker” such as valsartan, telmisartan, irbesartan etc. 

- ketoconazole, a medicine used to treat fungal infections. 

- verapamil, a medicine used to lower high blood pressure, to correct heart rhythm or to treat 

angina pectoris. 

- certain types of pain killers called non-steroidal anti-inflammatory medicines (NSAIDs). 

 

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Riprazo with food and drink 

You should take this medicine with a light meal once a day, preferably at the same time each day. You 

should not take this medicine together with grapefruit juice. 

 

Pregnancy and breast-feeding 

Do not take this medicine if you are pregnant or breast-feeding (see section Do not take Riprazo). If 

you think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for 

advice before taking this medicine. If you become pregnant while taking this medicine, stop taking it 

immediately and talk to your doctor. 

 

Driving and using machines 

This medicine may make you feel dizzy and this can affect your ability to concentrate. Before you 

drive a vehicle, use machinery, or carry out other activities that require concentration, you should 

make sure you know how you react to the effects of this medicine. 

 

 

3. How to take Riprazo 

 

Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist 

if you are not sure. 

 

People who have high blood pressure often do not notice any signs of the problem. Many may feel 

quite normal. It is very important that you take this medicine exactly as your doctor tells you to get the 

best results and reduce the risk of side effects. Keep your appointments with the doctor even if you 

are feeling well. 

 

The usual starting dose is one 150 mg tablet once daily. The blood pressure lowering effect is present 

within two weeks after beginning treatment. 

 

Depending on how you respond to the treatment your doctor may prescribe a higher dose of one 

300 mg tablet once daily. Your doctor may prescribe Riprazo together with other medicines used to 

treat high blood pressure. 

 

Method of administration 

It is recommended that you take the tablets with some water. You should take this medicine with a 

light meal once a day, preferably at the same time each day. You should not take this medicine 

together with grapefruit juice. 

 

If you take more Riprazo than you should 

If you have accidentally taken too many Riprazo tablets, consult a doctor immediately. You may 

require medical attention. 

 

If you forget to take Riprazo 

If you forget to take a dose of Riprazo, take it as soon as you remember and then take the next dose at 

its usual time. However, if it is almost time for your next dose you should simply take the next tablet 

at the usual time. Do not take a double dose to make up for a forgotten dose. 

 

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4. Possible side effects 

 

Like all medicines, this medicine can cause side effects, although not everybody gets them. 

 

Some side effects can be serious: 

A few patients have experienced these serious side effects (may affect up to 1 in 1,000 people). If any 

of the following occur, tell your doctor straight away: 

Severe allergic reaction with symptoms such as rash, itching, swelling of face or lips or tongue, 

difficulty breathing, dizziness. 

 

Possible side effects: 

Common (may affect up to 1 in 10 people): Diarrhoea, joint pain (arthralgia), high level of potassium 

in the blood, dizziness. 

Uncommon (may affect up to 1 in 100 people): Skin rash (this may also be a sign of allergic reactions 

or angioedema – see “Rare” side effects below), kidney problems including acute renal failure 

(severely decreased urine output), swelling of hands, ankles or feet (peripheral oedema), severe skin 

reactions (toxic epidermal necrolysis and/or oral mucosal reactions - red skin, blistering of the lips, 

eyes or mouth, skin peeling, fever), low blood pressure, palpitations, cough, itching, itchy rash 

(urticaria), increased liver enzymes. 

Rare (may affect up to 1 in 1,000 people): Severe allergic reaction (anaphylactic reaction), allergic 

reactions (hypersensitivity) and angioedema (the symptoms of which can include difficulties in 

breathing or swallowing, rash, itching, hives or swelling of the face, hands and feet, eyes, lips and/or 

tongue, dizziness), increased level of creatinine in the blood, red skin (erythema). 

 

If any of these affect you severely, tell your doctor. You may need to stop Riprazo. 

 

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 

not listed in this leaflet. 

 

 

5. How to store Riprazo 

 

Keep this medicine out of the sight and reach of children. 

Do not use this medicine after the expiry date which is stated on the carton and blister. The expiry 

date refers to the last day of that month. 

Do not store above 30°C. 

Store in the original package in order to protect from moisture. 

 

 

6. Contents of the pack and other information 

 

What Riprazo contains 

- The active substance is aliskiren (as hemifumarate) 300 mg. 

- The other ingredients are crospovidone, hypromellose, magnesium stearate, macrogol, 

microcrystalline cellulose, povidone, colloidal anhydrous silica, talc, titanium dioxide (E 171), 

black iron oxide (E 172), red iron oxide (E 172). 

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What Riprazo looks like and contents of the pack 

Riprazo 300 mg film coated tablets are light-red, biconvex, ovaloid tablets, imprinted “IU” on one 

side and “NVR” on the other side. 

 

Riprazo is available in packs containing 7, 14, 28, 30, 50, 56, 84, 90, 98 or 280 tablets. Packs 

containing 84 (3x28), 90 (3x30), 98 (2x49) or 280 (20x14) tablets are multi-packs. Not all pack sizes 

may be available in your country. 

 

 

Marketing Authorisation Holder 

Novartis Europharm Limited 

Wimblehurst Road 

Horsham 

West Sussex, RH12 5AB 

United Kingdom 

 

Manufacturer 

Novartis Farma S.p.A. 

Via Provinciale Schito 131 

I-80058 Torre Annunziata/NA 

Italy 

 

For any information about this medicine, please contact the local representative of the Marketing 

Authorisation Holder: 

 

België/Belgique/Belgien 

Novartis Pharma N.V. 

Tél/Tel: +32 2 246 16 11 

 

Luxembourg/Luxemburg 

Novartis Pharma GmbH 

Tél/Tel: +49 911 273 0 

 

България 

Novartis Pharma Services Inc. 

Тел.: +359 2 489 98 28 

 

Magyarország 

Novartis Hungária Kft. Pharma 

Tel.: +36 1 457 65 00 

Česká republika 

Novartis s.r.o. 

Tel: +420 225 775 111 

 

Malta 

Novartis Pharma Services Inc. 

Tel: +356 2122 2872 

Danmark 

Novartis Healthcare A/S 

Tlf: +45 39 16 84 00 

 

Nederland 

Novartis Pharma B.V. 

Tel: +31 26 37 82 111 

Deutschland 

Novartis Pharma GmbH 

Tel: +49 911 273 0 

 

Norge 

Novartis Norge AS 

Tlf: +47 23 05 20 00 

Eesti 

Novartis Pharma Services Inc. 

Tel: +372 66 30 810 

 

Österreich 

Novartis Pharma GmbH 

Tel: +43 1 86 6570 

Ελλάδα 

Novartis (Hellas) A.E.B.E. 

Τηλ: +30 210 281 17 12 

 

Polska 

Novartis Poland Sp. z o.o. 

Tel.: +48 22 375 4888 

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72 

 

España 

Laboratorios Dr. Esteve, S.A. 

Tel: +34 93 446 60 00 

 

Portugal 

Novartis Farma - Produtos Farmacêuticos, S.A. 

Tel: +351 21 000 8600 

France 

Novartis Pharma S.A.S. 

Tél: +33 1 55 47 66 00 

 

România 

Novartis Pharma Services Romania SRL 

Tel: +40 21 31299 01 

Ireland 

Novartis Ireland Limited 

Tel: +353 1 260 12 55 

 

Slovenija 

Novartis Pharma Services Inc. 

Tel: +386 1 300 75 50 

Ísland 

Vistor hf. 

Sími: +354 535 7000 

 

Slovenská republika 

Novartis Slovakia s.r.o. 

Tel: +421 2 5542 5439 

 

Italia 

Novartis Farma S.p.A. 

Tel: +39 02 96 54 1 

Suomi/Finland 

Novartis Finland Oy 

Puh/Tel: +358 (0)10 6133 200 

 

Κύπρος 

Novartis Pharma Services Inc. 

Τηλ: +357 22 690 690 

 

Sverige 

Novartis Sverige AB 

Tel: +46 8 732 32 00 

 

Latvija 

Novartis Pharma Services Inc. 

Tel: +371 67 887 070 

 

United Kingdom 

Novartis Pharmaceuticals UK Ltd. 

Tel: +44 1276 698370 

 

Lietuva 

Novartis Pharma Services Inc. 

Tel: +370 5 269 16 50 

 

 

 

This leaflet was last revised in 

 

Other sources of information 

Detailed information on this medicine is available on the European Medicines Agency website: 

http://www.ema.europa.eu 

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	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	A. LABELLING
	B. PACKAGE LEAFLET